研究者を探す
赤川 貢
2024年10月10日更新
- 職名
- 教授
- 電話
- 研究者総覧に該当データはありませんでした。
- 電子メール
- akagawa@tokushima-u.ac.jp
- 学歴
- 研究者総覧に該当データはありませんでした。
- 学位
- 博士(農学)
- 職歴・経歴
- 2022/4: 徳島大学 教授, 大学院医歯薬学研究部
- 専門分野・研究分野
- 研究者総覧に該当データはありませんでした。
2024年10月10日更新
- 専門分野・研究分野
- 研究者総覧に該当データはありませんでした。
- 担当経験のある授業科目
- 健康食品・漢方 (大学院)
国際栄養学特論 (大学院)
国際栄養学特論/International Nutrtiion (大学院)
栄養英語 (学部)
機能性食品設計学 (大学院)
機能素材開発学セミナー (大学院)
機能素材開発学実験 (大学院)
機能素材開発学演習 (大学院)
機能素材開発学特別実験 (大学院)
生命科学の研究手法 (大学院)
食品プロセス学 (学部)
食品プロセス学実習 (学部)
食品健康学演習 (学部)
食品学基礎 (学部)
食品学実験 (学部)
食品機能学セミナー (大学院)
食品機能学演習 (大学院)
食品機能学特別実験 (大学院)
食品機能学特論 (大学院)
食品生理機能科学実験 (大学院)
食品素材学 (学部)
食品衛生学 (学部)
食品衛生学実習 (学部) - 指導経験
- 研究者総覧に該当データはありませんでした。
2024年10月10日更新
- 専門分野・研究分野
- 研究者総覧に該当データはありませんでした。
- 研究テーマ
- 研究者総覧に該当データはありませんでした。
- 著書
- 研究者総覧に該当データはありませんでした。
- 論文
- Kazuto Ikemoto, Nur Mohamad Syafiqah Ishak and Mitsugu Akagawa :
The effects of pyrroloquinoline quinone disodium salt on brain function and physiological processes,
The Journal of Medical Investigation : JMI, Vol.71, No.1,2, 23-28, 2024.- (徳島大学機関リポジトリ)
- ● Metadata: 119429
- (出版サイトへのリンク)
- ● Publication site (DOI): 10.2152/jmi.71.23
- (文献検索サイトへのリンク)
- ● Search Scopus @ Elsevier (DOI): 10.2152/jmi.71.23
(徳島大学機関リポジトリ: 119429, DOI: 10.2152/jmi.71.23) Mana Kitao, Ai Yamaguchi, Takuma Tomioka, Kenji Kai, Yuki Kamei, Kenji Sugimoto and Mitsugu Akagawa :
Astaxanthin protects human ARPE-19 retinal pigment epithelium cells from blue light-induced phototoxicity by scavenging singlet oxygen.,
Free Radical Research, Vol.57, No.6-12, 430-443, 2023.- (要約)
- directly. Our results suggest the potential value of astaxanthin as a dietary strategy to prevent blue light-induced retinal degeneration including AMD.
- (キーワード)
- Humans / Aged / Singlet Oxygen / Reactive Oxygen Species / Blue Light / Retinal Pigment Epithelium / Oxidative Stress / Apoptosis / Xanthophylls / Macular Degeneration
- (出版サイトへのリンク)
- ● Publication site (DOI): 10.1080/10715762.2023.2277144
- (文献検索サイトへのリンク)
- ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 37897411
- ● Search Scopus @ Elsevier (PMID): 37897411
- ● Search Scopus @ Elsevier (DOI): 10.1080/10715762.2023.2277144
(DOI: 10.1080/10715762.2023.2277144, PubMed: 37897411) Nur Mohamad Syafiqah Ishak, Kazuto Ikemoto, Midori Kikuchi, Mariko Ogawa, Kazeno Akutagawa and Mitsugu Akagawa :
Pyrroloquinoline Quinone Attenuates Fat Accumulation in Obese Mice Fed with a High-Fat Diet, Daphnia magna Supplied with a High Amount of Food, and 3T3-L1 Adipocytes,
ACS Food Science and Technology, Vol.1, No.10, 1979-1989, 2021.- (出版サイトへのリンク)
- ● Publication site (DOI): 10.1021/acsfoodscitech.1c00301
- (文献検索サイトへのリンク)
- ● Search Scopus @ Elsevier (DOI): 10.1021/acsfoodscitech.1c00301
(DOI: 10.1021/acsfoodscitech.1c00301) Mitsugu Akagawa :
Protein carbonylation: molecular mechanisms, biological implications, and analytical approaches.,
Free Radical Research, Vol.55, No.4, 307-320, 2021.- (要約)
- Proteins are oxidatively modified by a large number of reactive species including reactive oxygen species, lipid peroxidation-derived aldehydes, and reducing sugars. Among divergent oxidative modifications, the introduction of carbonyl groups such as aldehyde, ketone, and lactam into the amino acid side chains of proteins is a major hallmark for oxidative damage to proteins, and is termed "protein carbonylation". Detection and quantification of protein carbonyls are commonly performed to determine the level of oxidative stress in the context of cellular damage, aging, and several age-related disorders. This review focuses on the molecular mechanisms and biological implications of protein carbonylation, and also presents current analytical approaches for determining and characterizing carbonylated proteins.
- (キーワード)
- Animals / Humans / Oxidation-Reduction / Protein Carbonylation / Proteins
- (出版サイトへのリンク)
- ● Publication site (DOI): 10.1080/10715762.2020.1851027
- (文献検索サイトへのリンク)
- ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 33183115
- ● Search Scopus @ Elsevier (PMID): 33183115
- ● Search Scopus @ Elsevier (DOI): 10.1080/10715762.2020.1851027
(DOI: 10.1080/10715762.2020.1851027, PubMed: 33183115) Kosuke Yamaguchi, Masanori Itakura, Roma Kitazawa, Sei-Young Lim, Koji Nagata, Takahiro Shibata, Mitsugu Akagawa and Koji Uchida :
Oxidative deamination of lysine residues by polyphenols generates an equilibrium of aldehyde and 2-piperidinol products.,
The Journal of Biological Chemistry, Vol.297, No.3, 2021.- (要約)
- Polyphenols, especially catechol-type polyphenols, exhibit lysyl oxidase-like activity and mediate oxidative deamination of lysine residues in proteins. Previous studies have shown that polyphenol-mediated oxidative deamination of lysine residues can be associated with altered electrical properties of proteins and increased crossreactivity with natural immunoglobulin M antibodies. This interaction suggested that oxidized proteins could act as innate antigens and elicit an innate immune response. However, the structural basis for oxidatively deaminated lysine residues remains unclear. In the present study, to establish the chemistry of lysine oxidation, we characterized oxidation products obtained via incubation of the lysine analog N-biotinyl-5-aminopentylamine with eggshell membranes containing lysyl oxidase and identified a unique six-membered ring 2-piperidinol derivative equilibrated with a ring-open product (aldehyde) as the major product. By monitoring these aldehyde-2-piperidinol products, we evaluated the lysyl oxidase-like activity of polyphenols. We also observed that this reaction was mediated by some polyphenols, especially o-diphenolic-type polyphenols, in the presence of copper ions. Interestingly, the natural immunoglobulin M monoclonal antibody recognized these aldehyde-2-piperidinol products as an innate epitope. These findings establish the existence of a dynamic equilibrium of oxidized lysine and provide important insights into the chemopreventive function of dietary polyphenols for chronic diseases.
- (キーワード)
- Aldehydes / Cyclization / Deamination / Lysine / Oxidation-Reduction / Piperidines / Polyphenols / Protein-Lysine 6-Oxidase
- (出版サイトへのリンク)
- ● Publication site (DOI): 10.1016/j.jbc.2021.101035
- (文献検索サイトへのリンク)
- ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 34339739
- ● Search Scopus @ Elsevier (PMID): 34339739
- ● Search Scopus @ Elsevier (DOI): 10.1016/j.jbc.2021.101035
(DOI: 10.1016/j.jbc.2021.101035, PubMed: 34339739) Moeri Oshimo, Fumie Nakashima, Kenji Kai, Hirofumi Matsui, Takahiro Shibata and Mitsugu Akagawa :
Sodium sulfite causes gastric mucosal cell death by inducing oxidative stress.,
Free Radical Research, Vol.55, No.6, 731-743, 2021.- (要約)
- -related free radicals.
- (キーワード)
- Animals / Cell Death / Oxidative Stress / Rats / Stomach / Sulfites
- (出版サイトへのリンク)
- ● Publication site (DOI): 10.1080/10715762.2021.1937620
- (文献検索サイトへのリンク)
- ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 34074194
- ● Search Scopus @ Elsevier (PMID): 34074194
- ● Search Scopus @ Elsevier (DOI): 10.1080/10715762.2021.1937620
(DOI: 10.1080/10715762.2021.1937620, PubMed: 34074194) Hikari Kusu, Hiroki Yoshida, Michiko Kudo, Mai Okuyama, Naoki Harada, Kentaro Tsuji-Naito and Mitsugu Akagawa :
Tomatidine Reduces Palmitate-Induced Lipid Accumulation by Activating AMPK via Vitamin D Receptor-Mediated Signaling in Human HepG2 Hepatocytes.,
Molecular Nutrition & Food Research, Vol.63, No.22, 2019.- (要約)
- The in vitro study suggests the potential efficacy of tomatidine as a preventive and therapeutic treatment in obesity-related fatty liver diseases.
- (キーワード)
- AMP-Activated Protein Kinases / Calcium / Calcium-Calmodulin-Dependent Protein Kinase Kinase / Enzyme Activation / Forkhead Box Protein O1 / Hep G2 Cells / Hepatocytes / Humans / Lipid Metabolism / Palmitates / Receptors, Calcitriol / Signal Transduction / Sterol Regulatory Element Binding Protein 1 / Tomatine
- (出版サイトへのリンク)
- ● Publication site (DOI): 10.1002/mnfr.201801377
- (文献検索サイトへのリンク)
- ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 31454158
- ● Search Scopus @ Elsevier (PMID): 31454158
- ● Search Scopus @ Elsevier (DOI): 10.1002/mnfr.201801377
(DOI: 10.1002/mnfr.201801377, PubMed: 31454158) Hiroki Yoshida, Megumi Ishii and Mitsugu Akagawa :
Propionate suppresses hepatic gluconeogenesis via GPR43/AMPK signaling pathway.,
Archives of Biochemistry and Biophysics, Vol.672, 2019.- (要約)
- increase, leading to suppression of gluconeogenesis. The present study suggests the potential efficacy of propionate in preventive and therapeutic management of diabetes.
- (キーワード)
- AMP-Activated Protein Kinases / Animals / Calcium-Calmodulin-Dependent Protein Kinase Kinase / Down-Regulation / Gluconeogenesis / Hep G2 Cells / Humans / Liver / Mice / Propionates / Receptors, Cell Surface / Signal Transduction
- (出版サイトへのリンク)
- ● Publication site (DOI): 10.1016/j.abb.2019.07.022
- (文献検索サイトへのリンク)
- ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 31356781
- ● Search Scopus @ Elsevier (PMID): 31356781
- ● Search Scopus @ Elsevier (DOI): 10.1016/j.abb.2019.07.022
(DOI: 10.1016/j.abb.2019.07.022, PubMed: 31356781) Miho Yagi, Yukiko Nakatsuji, Ayumi Maeda, Hiroki Ota, Ryosuke Kamikubo, Noriyuki Miyoshi, Yoshimasa Nakamura and Mitsugu Akagawa :
Phenethyl isothiocyanate activates leptin signaling and decreases food intake.,
PLoS ONE, Vol.13, No.11, 2018.- (要約)
- Obesity, a principal risk factor for the development of diabetes mellitus, heart disease, and hypertension, is a growing and serious health problem all over the world. Leptin is a weight-reducing hormone produced by adipose tissue, which decreases food intake via hypothalamic leptin receptors (Ob-Rb) and the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway. Protein tyrosine phosphatase 1B (PTP1B) negatively regulates leptin signaling by dephosphorylating JAK2, and the increased activity of PTP1B is implicated in the pathogenesis of obesity. Hence, inhibition of PTP1B may help prevent and reduce obesity. In this study, we revealed that phenethyl isothiocyanate (PEITC), a naturally occurring isothiocyanate in certain cruciferous vegetables, potently inhibits recombinant PTP1B by binding to the reactive cysteinyl thiol. Moreover, we found that PEITC causes the ligand-independent phosphorylation of Ob-Rb, JAK2, and STAT3 by inhibiting cellular PTP1B in differentiated human SH-SY5Y neuronal cells. PEITC treatment also induced nuclear accumulation of phosphorylated STAT3, resulting in enhanced anorexigenic POMC expression and suppressed orexigenic NPY/AGRP expression. We demonstrated that oral administration of PEITC to mice significantly reduces food intake, and stimulates hypothalamic leptin signaling. Our results suggest that PEITC might help prevent and improve obesity.
- (キーワード)
- Administration, Oral / Animals / Anti-Obesity Agents / Cell Line, Tumor / Cell Nucleus / Dose-Response Relationship, Drug / Eating / Humans / Hypothalamus / Isothiocyanates / Leptin / Male / Mice, Inbred C57BL / Neurons / Obesity / RNA, Messenger / STAT3 Transcription Factor / Signal Transduction
- (徳島大学機関リポジトリ)
- ● Metadata: 117761
- (出版サイトへのリンク)
- ● Publication site (DOI): 10.1371/journal.pone.0206748
- (文献検索サイトへのリンク)
- ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 30383868
- ● Search Scopus @ Elsevier (PMID): 30383868
- ● Search Scopus @ Elsevier (DOI): 10.1371/journal.pone.0206748
(徳島大学機関リポジトリ: 117761, DOI: 10.1371/journal.pone.0206748, PubMed: 30383868) Ayumi Maeda, Takeshi Shirao, Daishi Shirasaya, Yasukiyo Yoshioka, Yoko Yamashita, Mitsugu Akagawa and Hitoshi Ashida :
Piperine Promotes Glucose Uptake through ROS-Dependent Activation of the CAMKK/AMPK Signaling Pathway in Skeletal Muscle.,
Molecular Nutrition & Food Research, Vol.62, No.11, 2018.- (要約)
- /calmodulin-dependent protein kinase kinase-beta (CaMKKβ) as the upstream events for AMPK phosphorylation. Furthermore, oral administration of piperine to Wistar rats at 0.01 and 0.1 mg kg
- (キーワード)
- AMP-Activated Protein Kinases / Alkaloids / Animals / Benzodioxoles / Calcium / Calcium-Calmodulin-Dependent Protein Kinase Kinase / Cell Line / Glucose / Glucose Tolerance Test / Glucose Transporter Type 4 / Hypoglycemic Agents / Male / Muscle, Skeletal / Phosphorylation / Piperidines / Polyunsaturated Alkamides / Rats, Wistar / Reactive Oxygen Species / Signal Transduction / Spices / TRPV Cation Channels
- (出版サイトへのリンク)
- ● Publication site (DOI): 10.1002/mnfr.201800086
- (文献検索サイトへのリンク)
- ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 29683271
- ● Search Scopus @ Elsevier (PMID): 29683271
- ● Search Scopus @ Elsevier (DOI): 10.1002/mnfr.201800086
(DOI: 10.1002/mnfr.201800086, PubMed: 29683271) Kazuhiro Saihara, Ryosuke Kamikubo, Kazuto Ikemoto, Koji Uchida and Mitsugu Akagawa :
Pyrroloquinoline Quinone, a Redox-Active o-Quinone, Stimulates Mitochondrial Biogenesis by Activating the SIRT1/PGC-1α Signaling Pathway.,
Biochemistry, Vol.56, No.50, 6615-6625, 2017.- (要約)
- formation.
- (キーワード)
- Animals / Benzoquinones / Fibroblasts / Hep G2 Cells / Humans / Mice / Mitochondria / NIH 3T3 Cells / Organelle Biogenesis / Oxidation-Reduction / PQQ Cofactor / Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Signal Transduction / Sirtuin 1 / Trans-Activators / Transcription Factors
- (出版サイトへのリンク)
- ● Publication site (DOI): 10.1021/acs.biochem.7b01185
- (文献検索サイトへのリンク)
- ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 29185343
- ● Search Scopus @ Elsevier (PMID): 29185343
- ● Search Scopus @ Elsevier (DOI): 10.1021/acs.biochem.7b01185
(DOI: 10.1021/acs.biochem.7b01185, PubMed: 29185343) Mai Furuhashi, Yukinori Hatasa, Sae Kawamura, Takahiro Shibata, Mitsugu Akagawa and Koji Uchida :
Identification of Polyphenol-Specific Innate Epitopes That Originated from a Resveratrol Analogue.,
Biochemistry, Vol.56, No.35, 4701-4712, 2017.- (要約)
- Polyphenols have received a significant amount of attention in disease prevention because of their unique chemical and biological properties. However, the underlying molecular mechanism for their beneficial effects remains unclear. We have now identified a polyphenol as a source of innate epitopes detected in natural IgM and established a unique gain-of-function mechanism in the formation of innate epitopes by polyphenol via the polymerization of proteins. Upon incubation with bovine serum albumin (BSA) under physiological conditions, several polyphenols converted the protein into the innate epitopes recognized by the IgM Abs. Interestingly, piceatannol, a naturally occurring hydroxylated analogue of a red wine polyphenol, resveratrol, mediated the modification of BSA, whose polymerized form was specifically recognized by the IgMs. The piceatannol-mediated polymerization of the protein was associated with the formation of a lysine-derived cross-link, dehydrolysinonorleucine. In addition, an oxidatively deaminated product, α-aminoadipic semialdehyde, was detected as a potential precursor for the cross-link in the piceatannol-treated BSA, suggesting that the polymerization of the protein might be mediated by the oxidation of a lysine residue by piceatannol followed by a Schiff base reaction with the ε-amino group of an unoxidized lysine residue. The results of this study established a novel mechanism for the formation of innate epitopes by small dietary molecules and support the notion that many of the beneficial effects of polyphenols could be attributed, at least in part, to their lysyl oxidase-like activity. They also suggest that resveratrol may have beneficial effects on human health because of its conversion to piceatannol.
- (キーワード)
- Aging / Animals / Epitopes / Female / Immunoglobulin M / Mice / Mice, Inbred Strains / Molecular Structure / Polyphenols / Resveratrol / Serum Albumin, Bovine / Stilbenes
- (出版サイトへのリンク)
- ● Publication site (DOI): 10.1021/acs.biochem.7b00409
- (文献検索サイトへのリンク)
- ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 28796948
- ● Search Scopus @ Elsevier (PMID): 28796948
- ● Search Scopus @ Elsevier (DOI): 10.1021/acs.biochem.7b00409
(DOI: 10.1021/acs.biochem.7b00409, PubMed: 28796948) Mia Imanishi, Motohiro Sonoda, Hironari Miyazato, Keiichiro Sugimoto, Mitsugu Akagawa and Shinji Tanimori :
Sequential Synthesis, Olfactory Properties, and Biological Activity of Quinoxaline Derivatives.,
ACS Omega, Vol.2, No.5, 1875-1885, 2017.- (要約)
- has been achieved, based on the copper-catalyzed quinoxalinone formation of 2-haloanilines and amino acids followed by their reduction and oxidation. The olfactory properties and lipid accumulation inhibitory activity in cultured hepatocytes of the quinoxaline derivatives were also evaluated.
- (出版サイトへのリンク)
- ● Publication site (DOI): 10.1021/acsomega.7b00124
- (文献検索サイトへのリンク)
- ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 30023648
- ● Search Scopus @ Elsevier (PMID): 30023648
- ● Search Scopus @ Elsevier (DOI): 10.1021/acsomega.7b00124
(DOI: 10.1021/acsomega.7b00124, PubMed: 30023648) Kohei Dainin, Ryoko Ide, Ayumi Maeda, Kyozo Suyama and Mitsugu Akagawa :
Pyridoxamine scavenges protein carbonyls and inhibits protein aggregation in oxidative stress-induced human HepG2 hepatocytes.,
Biochemical and Biophysical Research Communications, Vol.486, No.3, 845-851, 2017.- (要約)
- -exposed HepG2 hepatocytes with PM significantly reduced levels of cellular carbonylated proteins and aggregated proteins, and also improved cell survival rate. Our results suggest that PM may have potential efficacy in ameliorating ROS-mediated cellular dysfunction.
- (キーワード)
- Antioxidants / Hep G2 Cells / Humans / Hydrogen Peroxide / Muramidase / Oxidation-Reduction / Oxidative Stress / Protein Aggregates / Protein Carbonylation / Pyridoxamine / Reactive Oxygen Species
- (出版サイトへのリンク)
- ● Publication site (DOI): 10.1016/j.bbrc.2017.03.147
- (文献検索サイトへのリンク)
- ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 28359757
- ● Search Scopus @ Elsevier (PMID): 28359757
- ● Search Scopus @ Elsevier (DOI): 10.1016/j.bbrc.2017.03.147
(DOI: 10.1016/j.bbrc.2017.03.147, PubMed: 28359757) Ryosuke Kamikubo, Kenji Kai, Kentaro Tsuji-Naito and Mitsugu Akagawa :
β-Caryophyllene attenuates palmitate-induced lipid accumulation through AMPK signaling by activating CB2 receptor in human HepG2 hepatocytes.,
Molecular Nutrition & Food Research, Vol.60, No.10, 2228-2242, 2016.- (要約)
- Our results suggest that β-caryophyllene has the potential efficacy in preventing and ameliorating nonalcoholic fatty liver disease and its associated metabolic disorders.
- (キーワード)
- AMP-Activated Protein Kinases / Calcium / Forkhead Box Protein O1 / Hep G2 Cells / Hepatocytes / Humans / Lipid Metabolism / Non-alcoholic Fatty Liver Disease / Palmitates / Phosphorylation / Plant Extracts / Polycyclic Sesquiterpenes / Receptor, Cannabinoid, CB2 / Sesquiterpenes / Signal Transduction / Sterol Regulatory Element Binding Protein 1 / Syzygium
- (出版サイトへのリンク)
- ● Publication site (DOI): 10.1002/mnfr.201600197
- (文献検索サイトへのリンク)
- ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 27234712
- ● Search Scopus @ Elsevier (PMID): 27234712
- ● Search Scopus @ Elsevier (DOI): 10.1002/mnfr.201600197
(DOI: 10.1002/mnfr.201600197, PubMed: 27234712) Mitsugu Akagawa, Kenji Minematsu, Takahiro Shibata, Tatsuhiko Kondo, Takeshi Ishii and Koji Uchida :
Identification of lactate dehydrogenase as a mammalian pyrroloquinoline quinone (PQQ)-binding protein.,
Scientific Reports, Vol.6, 2016.- (要約)
- Pyrroloquinoline quinone (PQQ), a redox-active o-quinone, is an important nutrient involved in numerous physiological and biochemical processes in mammals. Despite such beneficial functions, the underlying molecular mechanisms remain to be established. In the present study, using PQQ-immobilized Sepharose beads as a probe, we examined the presence of protein(s) that are capable of binding PQQ in mouse NIH/3T3 fibroblasts and identified five cellular proteins, including l-lactate dehydrogenase (LDH) A chain, as potential mammalian PQQ-binding proteins. In vitro studies using a purified rabbit muscle LDH show that PQQ inhibits the formation of lactate from pyruvate in the presence of NADH (forward reaction), whereas it enhances the conversion of lactate to pyruvate in the presence of NAD(+) (reverse reaction). The molecular mechanism underlying PQQ-mediated regulation of LDH activity is attributed to the oxidation of NADH to NAD(+) by PQQ. Indeed, the PQQ-bound LDH oxidizes NADH, generating NAD(+), and significantly catalyzes the conversion of lactate to pyruvate. Furthermore, PQQ attenuates cellular lactate release and increases intracellular ATP levels in the NIH/3T3 fibroblasts. Our results suggest that PQQ, modulating LDH activity to facilitate pyruvate formation through its redox-cycling activity, may be involved in the enhanced energy production via mitochondrial TCA cycle and oxidative phosphorylation.
- (キーワード)
- Animals / L-Lactate Dehydrogenase / Mice / NIH 3T3 Cells / PQQ Cofactor / Protein Binding / Rabbits
- (徳島大学機関リポジトリ)
- ● Metadata: 117765
- (出版サイトへのリンク)
- ● Publication site (DOI): 10.1038/srep26723
- (文献検索サイトへのリンク)
- ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 27230956
- ● Search Scopus @ Elsevier (PMID): 27230956
- ● Search Scopus @ Elsevier (DOI): 10.1038/srep26723
(徳島大学機関リポジトリ: 117765, DOI: 10.1038/srep26723, PubMed: 27230956) Michiko Kudo, Takeshi Katayoshi, Kumiko Kobayashi-Nakamura, Mitsugu Akagawa and Kentaro Tsuji-Naito :
H(+)/peptide transporter (PEPT2) is expressed in human epidermal keratinocytes and is involved in skin oligopeptide transport.,
Biochemical and Biophysical Research Communications, Vol.475, No.4, 335-341, 2016.- (要約)
- Peptide transporter 2 (PEPT2) is a member of the proton-coupled oligopeptide transporter family, which mediates the cellular uptake of oligopeptides and peptide-like drugs. Although PEPT2 is expressed in many tissues, its expression in epidermal keratinocytes remains unclear. We investigated PEPT2 expression profile and functional activity in keratinocytes. We confirmed PEPT2 mRNA expression in three keratinocyte lines (normal human epidermal keratinocytes (NHEKs), immortalized keratinocytes, and malignant keratinocytes) by reverse transcription-polymerase chain reaction (RT-PCR) and quantitative real-time RT-PCR. In contrast to PEPT1, PEPT2 expression in the three keratinocytes was similar or higher than that in HepG2 cells, used as PEPT2-positive cells. Immunolocalization analysis using human skin showed epidermal PEPT2 localization. We studied keratinocyte transport function by measuring the oligopeptide content using liquid chromatography/tandem mass spectrometry. Glycylsarcosine uptake in NHEKs was pH-dependent, suggesting that keratinocytes could absorb small peptides in the presence of an inward H(+) gradient. We also performed a skin-permeability test of several oligopeptides using skin substitute, suggesting that di- and tripeptides pass actively through the epidermis. In conclusion, PEPT2 is expressed in keratinocytes and involved in skin oligopeptide uptake.
- (キーワード)
- Adult / Biological Transport / Cells, Cultured / Epidermal Cells / Epidermis / Female / Gene Expression / Humans / Keratinocytes / Male / Oligopeptides / RNA, Messenger / Symporters
- (出版サイトへのリンク)
- ● Publication site (DOI): 10.1016/j.bbrc.2016.05.093
- (文献検索サイトへのリンク)
- ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 27216463
- ● Search Scopus @ Elsevier (PMID): 27216463
- ● Search Scopus @ Elsevier (DOI): 10.1016/j.bbrc.2016.05.093
(DOI: 10.1016/j.bbrc.2016.05.093, PubMed: 27216463) Yukinori Hatasa, Miho Chikazawa, Mai Furuhashi, Fumie Nakashima, Takahiro Shibata, Tatsuhiko Kondo, Mitsugu Akagawa, Hiroki Hamagami, Hiroshi Tanaka, Hirofumi Tachibana and Koji Uchida :
Oxidative Deamination of Serum Albumins by (-)-Epigallocatechin-3-O-Gallate: A Potential Mechanism for the Formation of Innate Antigens by Antioxidants.,
PLoS ONE, Vol.11, No.4, 2016.- (要約)
- (-)-Epigallocatechin-3-O-gallate (EGCG), the most abundant polyphenol in green tea, mediates the oxidative modification of proteins, generating protein carbonyls. However, the underlying molecular mechanism remains unclear. Here we analyzed the EGCG-derived intermediates generated upon incubation with the human serum albumin (HSA) and established that EGCG selectively oxidized the lysine residues via its oxidative deamination activity. In addition, we characterized the EGCG-oxidized proteins and discovered that the EGCG could be an endogenous source of the electrically-transformed proteins that could be recognized by the natural antibodies. When HSA was incubated with EGCG in the phosphate-buffered saline (pH 7.4) at 37°C, the protein carbonylation was associated with the formation of EGCG-derived products, such as the protein-bound EGCG, oxidized EGCG, and aminated EGCG. The aminated EGCG was also detected in the sera from the mice treated with EGCG in vivo. EGCG selectively oxidized lysine residues at the EGCG-binding domains in HSA to generate an oxidatively deaminated product, aminoadipic semialdehyde. In addition, EGCG treatment results in the increased negative charge of the protein due to the oxidative deamination of the lysine residues. More strikingly, the formation of protein carbonyls by EGCG markedly increased its cross-reactivity with the natural IgM antibodies. These findings suggest that many of the beneficial effects of EGCG may be partly attributed to its oxidative deamination activity, generating the oxidized proteins as a target of natural antibodies.
- (キーワード)
- Animals / Antigens / Antioxidants / Catechin / Chromatography, Liquid / Click Chemistry / Deamination / Female / Immunity, Innate / Mice / Mice, Inbred BALB C / Oxidation-Reduction / Serum Albumin / Spectrometry, Mass, Electrospray Ionization
- (徳島大学機関リポジトリ)
- ● Metadata: 117759
- (出版サイトへのリンク)
- ● Publication site (DOI): 10.1371/journal.pone.0153002
- (文献検索サイトへのリンク)
- ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 27046229
- ● Search Scopus @ Elsevier (PMID): 27046229
- ● Search Scopus @ Elsevier (DOI): 10.1371/journal.pone.0153002
(徳島大学機関リポジトリ: 117759, DOI: 10.1371/journal.pone.0153002, PubMed: 27046229) Norio Yamamoto, Manabu Ueda-Wakagi, Takuya Sato, Kengo Kawasaki, Keisuke Sawada, Kyuichi Kawabata, Mitsugu Akagawa and Hitoshi Ashida :
Measurement of Glucose Uptake in Cultured Cells.,
Current Protocols in Pharmacology, Vol.71, 12.14.1-12.14.26, 2015.- (要約)
- Facilitative glucose uptake transport systems are ubiquitous in animal cells and are responsible for transporting glucose across cell surface membranes. Evaluation of glucose uptake is crucial in the study of numerous diseases and metabolic disorders such as myocardial ischemia, diabetes mellitus, and cancer. Detailed in this unit are laboratory methods for assessing glucose uptake into mammalian cells. The unit is divided into five sections: (1) a brief overview of glucose uptake assays in cultured cells; (2) a method for measuring glucose uptake using radiolabeled 3-O-methylglucose; (3) a method for measuring glucose uptake using radiolabeled 2-deoxyglucose (2DG); (4) a microplate method for measuring 2DG-uptake using an enzymatic, fluorometric assay; and (5) a microplate-based method using a fluorescent analog of 2DG.
- (キーワード)
- 3-O-Methylglucose / Animals / Biological Transport / Cells, Cultured / Deoxyglucose / Fluorescent Dyes / Fluorometry / Glucose / Humans
- (出版サイトへのリンク)
- ● Publication site (DOI): 10.1002/0471141755.ph1214s71
- (文献検索サイトへのリンク)
- ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 26646194
- ● Search Scopus @ Elsevier (PMID): 26646194
- ● Search Scopus @ Elsevier (DOI): 10.1002/0471141755.ph1214s71
(DOI: 10.1002/0471141755.ph1214s71, PubMed: 26646194) Mitsugu Akagawa, Masahiko Nakano and Kazuto Ikemoto :
Recent progress in studies on the health benefits of pyrroloquinoline quinone.,
Bioscience, Biotechnology, and Biochemistry, Vol.80, No.1, 13-22, 2015.- (要約)
- Pyrroloquinoline quinone (PQQ), an aromatic tricyclic o-quinone, was identified initially as a redox cofactor for bacterial dehydrogenases. Although PQQ is not biosynthesized in mammals, trace amounts of PQQ have been found in human and rat tissues because of its wide distribution in dietary sources. Importantly, nutritional studies in rodents have revealed that PQQ deficiency exhibits diverse systemic responses, including growth impairment, immune dysfunction, and abnormal reproductive performance. Although PQQ is not currently classified as a vitamin, PQQ has been implicated as an important nutrient in mammals. In recent years, PQQ has been receiving much attention owing to its physiological importance and pharmacological effects. In this article, we review the potential health benefits of PQQ with a focus on its growth-promoting activity, anti-diabetic effect, anti-oxidative action, and neuroprotective function. Additionally, we provide an update of its basic pharmacokinetics and safety information in oral ingestion.
- (キーワード)
- Animals / Antioxidants / Dietary Supplements / Gene Expression Regulation / Glucose / Humans / Hypoglycemic Agents / Insulin / Maze Learning / Memory / Neuroprotective Agents / Oxidation-Reduction / PQQ Cofactor / Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Rats / Receptor, Insulin
- (出版サイトへのリンク)
- ● Publication site (DOI): 10.1080/09168451.2015.1062715
- (文献検索サイトへのリンク)
- ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 26168402
- ● Search Scopus @ Elsevier (PMID): 26168402
- ● Search Scopus @ Elsevier (DOI): 10.1080/09168451.2015.1062715
(DOI: 10.1080/09168451.2015.1062715, PubMed: 26168402) Tri Handoyo, Mitsugu Akagawa and Kyung-Min Kim :
Production of Hypoallergenic Cocoa Beans by a Pregermination Treatment Method,
Journal of Plant Biotechnology, Vol.42, 123-128, 2015. Megumi Ishii, Ayumi Maeda, Shuji Tani and Mitsugu Akagawa :
Palmitate induces insulin resistance in human HepG2 hepatocytes by enhancing ubiquitination and proteasomal degradation of key insulin signaling molecules.,
Archives of Biochemistry and Biophysics, Vol.566, 26-35, 2014.- (要約)
- Obesity-associated insulin resistance is a major pathogenesis of type 2 diabetes mellitus and is characterized by defects in insulin signaling. High concentrations of plasma free fatty acids (FFAs) are involved in the etiology of obesity-associated insulin resistance. However, the detailed mechanism by which FFAs contribute to the development of insulin resistance is not yet fully understood. We investigated the molecular basis of insulin resistance elicited by FFAs using the human hepatocyte cell line HepG2. Among major human FFAs, palmitate markedly inhibited insulin-stimulated phosphorylation of key insulin signaling molecules such as insulin receptor, insulin receptor substrate-1, and Akt, indicating that palmitate is the principal inducer of insulin resistance. We revealed that palmitate facilitates ubiquitination of the key insulin signaling molecules, and subsequently elicits their proteasomal degradation. Furthermore, we demonstrated that inhibition of ubiquitination by the ubiquitin-activating enzyme E1 inhibitor PYR41 significantly prevents palmitate-inducible insulin resistance but not by the proteasome inhibitor MG132, implying that ubiquitinated signaling molecules may be dysfunctional. In conclusion, inhibition of ubiquitination of the key insulin signaling molecules may be a potential strategy for preventing and treating obesity-associated insulin resistance.
- (キーワード)
- Benzoates / Fatty Acids, Nonesterified / Furans / Gene Expression Regulation / Hep G2 Cells / Humans / Insulin / Insulin Receptor Substrate Proteins / Insulin Resistance / Leupeptins / Palmitic Acid / Phosphorylation / Proteasome Endopeptidase Complex / Proteolysis / Proto-Oncogene Proteins c-akt / Pyrazoles / Receptor, Insulin / Signal Transduction / Ubiquitin-Activating Enzymes / Ubiquitination
- (出版サイトへのリンク)
- ● Publication site (DOI): 10.1016/j.abb.2014.12.009
- (文献検索サイトへのリンク)
- ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 25527164
- ● Search Scopus @ Elsevier (PMID): 25527164
- ● Search Scopus @ Elsevier (DOI): 10.1016/j.abb.2014.12.009
(DOI: 10.1016/j.abb.2014.12.009, PubMed: 25527164) Kenji Kai, Hiroki Fujii, Rui Ikenaka, Mitsugu Akagawa and Hideo Hayashi :
An acyl-SAM analog as an affinity ligand for identifying quorum sensing signal synthases.,
Chemical Communications, Vol.50, No.62, 8586-8589, 2014.- (要約)
- N-Acylhomoserine lactones (AHLs) are quorum sensing signals produced by Gram-negative bacteria. We here report the affinity purification of AHL synthases using beads conjugated with an enzyme inhibitor, which was designed based on the catalytic intermediate acyl-SAM.
- (キーワード)
- Acyl-Butyrolactones / Enzyme Inhibitors / Kinetics / Ligases / Models, Molecular / Molecular Docking Simulation / S-Adenosylmethionine / Structure-Activity Relationship
- (出版サイトへのリンク)
- ● Publication site (DOI): 10.1039/c4cc03094j
- (文献検索サイトへのリンク)
- ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 24955553
- ● Search Scopus @ Elsevier (PMID): 24955553
- ● Search Scopus @ Elsevier (DOI): 10.1039/c4cc03094j
(DOI: 10.1039/c4cc03094j, PubMed: 24955553) Ayumi Maeda, Kenji Kai, Megumi Ishii, Takeshi Ishii and Mitsugu Akagawa :
Safranal, a novel protein tyrosine phosphatase 1B inhibitor, activates insulin signaling in C2C12 myotubes and improves glucose tolerance in diabetic KK-Ay mice.,
Molecular Nutrition & Food Research, Vol.58, No.6, 1177-1189, 2014.- (要約)
- Our results strongly suggest the usefulness of safranal in antidiabetic treatment for type 2 diabetic subjects.
- (キーワード)
- Animals / Crocus / Cyclohexenes / Diabetes Mellitus, Type 2 / Female / Glucose Intolerance / Hypoglycemic Agents / Insulin Resistance / Male / Mice / Mice, Inbred Strains / Muscle Fibers, Skeletal / Myoblasts / Plant Extracts / Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Signal Transduction / Terpenes
- (出版サイトへのリンク)
- ● Publication site (DOI): 10.1002/mnfr.201300675
- (文献検索サイトへのリンク)
- ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 24668740
- ● Search Scopus @ Elsevier (PMID): 24668740
- ● Search Scopus @ Elsevier (DOI): 10.1002/mnfr.201300675
(DOI: 10.1002/mnfr.201300675, PubMed: 24668740) Mayumi Takada, Mika Sumi, Ayumi Maeda, Fumiko Watanabe, Toshikazu Kamiya, Takeshi Ishii, Masahiko Nakano and Mitsugu Akagawa :
Pyrroloquinoline quinone, a novel protein tyrosine phosphatase 1B inhibitor, activates insulin signaling in C2C12 myotubes and improves impaired glucose tolerance in diabetic KK-A(y) mice.,
Biochemical and Biophysical Research Communications, Vol.428, No.2, 315-320, 2012.- (要約)
- Insulin resistance is a pathological hallmark of type 2 diabetes mellitus and is characterized by defects in insulin signaling. Protein tyrosine phosphatase 1B (PTP1B) negatively regulates insulin signaling by tyrosine dephosphorylation of insulin receptor, and increased activity and expression of PTP1B is implicated in the pathogenesis of insulin resistance. Therefore, inhibition of PTP1B is anticipated to improve insulin resistance in type 2 diabetic subjects. Pyrroloquinoline quinone (PQQ), a redox cofactor for bacterial dehydrogenases, inhibits PTP1B to oxidatively modify the catalytic cysteine through its redox cycling activity. Here, we report that PQQ induces the ligand-independent activation of insulin signaling by inhibiting cellular PTP1B and enhances glucose uptake through the translocation of glucose transporter 4 in mouse C2C12 myotubes. Furthermore, we demonstrated that oral administration of PQQ improved impaired glucose tolerance in type 2 diabetic KK-A(y) mice. Our results strongly suggest that PQQ can be useful in anti-diabetic treatment for type 2 diabetic subjects.
- (キーワード)
- Animals / Diabetes Mellitus, Experimental / Diabetes Mellitus, Type 2 / Enzyme Inhibitors / Glucose Intolerance / Glucose Transporter Type 4 / Insulin / Mice / Mice, Inbred Strains / Muscle Fibers, Skeletal / PQQ Cofactor / Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Signal Transduction
- (出版サイトへのリンク)
- ● Publication site (DOI): 10.1016/j.bbrc.2012.10.055
- (文献検索サイトへのリンク)
- ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 23085227
- ● Search Scopus @ Elsevier (PMID): 23085227
- ● Search Scopus @ Elsevier (DOI): 10.1016/j.bbrc.2012.10.055
(DOI: 10.1016/j.bbrc.2012.10.055, PubMed: 23085227) Kazuki Kimura, Mayumi Takada, Takeshi Ishii, Kentaro Tsuji-Naito and Mitsugu Akagawa :
Pyrroloquinoline quinone stimulates epithelial cell proliferation by activating epidermal growth factor receptor through redox cycling.,
Free Radical Biology and Medicine, Vol.53, No.6, 1239-1251, 2012.- (要約)
- Pyrroloquinoline quinone (PQQ), a redox cofactor for bacterial dehydrogenases, has been implicated to be an important nutrient in mammals functioning as a potent growth factor. However, the underlying molecular mechanisms have not been elucidated. The present study revealed that PQQ induces the activation (tyrosine autophosphorylation) of epidermal growth factor receptor (EGFR) and its downstream signaling in a ligand-independent manner, leading to increased cellular proliferation in an epithelial cell line A431. PQQ inhibited protein tyrosine phosphatase 1B (PTP1B), which negatively regulates the EGFR signaling by tyrosine dephosphorylation, to oxidatively modify the catalytic cysteine through its redox cycling activity to generate H(2)O(2). PQQ-inducible intracellular ROS production and EGFR activation were significantly suppressed by the pre-treatment with antioxidants. The intracellular redox state regulates the EGFR signaling through the redox-sensitive catalytic cysteine of PTP1B and modulates cell proliferation. Our data suggest that PQQ may stimulate epithelial cell proliferation by activating EGFR by oxidation and subsequent inactivation of PTP1B via its redox cycling. Our results provide novel insight into the mechanisms by which PQQ may function as a growth factor to contribute to mammalian growth.
- (キーワード)
- Cell Line, Tumor / Cell Proliferation / Cyclin D1 / Epithelial Cells / ErbB Receptors / Extracellular Signal-Regulated MAP Kinases / G1 Phase Cell Cycle Checkpoints / Growth Substances / Humans / MAP Kinase Signaling System / Oxidation-Reduction / PQQ Cofactor / Phosphorylation / Protein Processing, Post-Translational / Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Reactive Oxygen Species / Up-Regulation
- (出版サイトへのリンク)
- ● Publication site (DOI): 10.1016/j.freeradbiomed.2012.07.015
- (文献検索サイトへのリンク)
- ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 22824864
- ● Search Scopus @ Elsevier (PMID): 22824864
- ● Search Scopus @ Elsevier (DOI): 10.1016/j.freeradbiomed.2012.07.015
(DOI: 10.1016/j.freeradbiomed.2012.07.015, PubMed: 22824864) Takuya Maeshima, Kazuya Honda, Miho Chikazawa, Takahiro Shibata, Yoshichika Kawai, Mitsugu Akagawa and Koji Uchida :
Quantitative analysis of acrolein-specific adducts generated during lipid peroxidation-modification of proteins in vitro: identification of N(τ)-(3-propanal)histidine as the major adduct.,
Chemical Research in Toxicology, Vol.25, No.7, 1384-1392, 2012.- (要約)
- Acrolein, a ubiquitous pollutant in the environment, is endogenously formed through oxidation reactions and is believed to be involved in cytopathological effects observed during oxidative stress. Acrolein exerts these effects because of its facile reactivity with biological materials, particularly proteins. In the present study, we quantitatively analyzed the acrolein-specific adducts generated during lipid peroxidation-modification of proteins and identified the acrolein adduct most abundantly generated in the in vitro oxidized low-density lipoproteins (LDL). Taking advantage of the fact that the acrolein-lysine adducts, N(ε)-(3-formyl-3,4-dehydropiperidino)lysine (FDP-lysine) and N(ε)-(3-methylpyridinium)lysine (MP-lysine), have stable core structures resistant to the acid hydrolysis condition of proteins, we examined the formation of these adducts in proteins using high performance liquid chromatography with online electrospray ionization tandem mass spectrometry. However, only MP-lysine was detected as a minor product in the iron/ascorbate-mediated oxidation of polyunsaturated fatty acids in the presence of proteins and in the oxidized low-density lipoproteins (LDL). However, using a reductive amination-based pyridylamination method, we analyzed the acrolein-specific adducts with a carbonyl functionality and found that acrolein modification of the protein produced a number of carbonylated amino acids, including an acrolein-histidine adduct. On the basis of the chemical and spectroscopic evidence, this adduct was identified as N(τ)-(3-propanal)histidine. More notably, N(τ)-(3-propanal)histidine appeared to be one of the major adducts generated in the oxidized LDL. These data suggest that acrolein generated during lipid peroxidation may primarily react with histidine residues of proteins to form N(τ)-(3-propanal)histidine.
- (キーワード)
- Acrolein / Aldehydes / Animals / Cattle / Chromatography, High Pressure Liquid / Environmental Pollutants / Histidine / Isotope Labeling / Lipid Peroxidation / Lipoproteins, LDL / Lysine / Oxidation-Reduction / Proteins / Serum Albumin, Bovine / Spectrometry, Mass, Electrospray Ionization
- (出版サイトへのリンク)
- ● Publication site (DOI): 10.1021/tx3000818
- (文献検索サイトへのリンク)
- ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 22716039
- ● Search Scopus @ Elsevier (PMID): 22716039
- ● Search Scopus @ Elsevier (DOI): 10.1021/tx3000818
(DOI: 10.1021/tx3000818, PubMed: 22716039) Naoko Takasao, Kentaro Tsuji-Naito, Seiko Ishikura, Azusa Tamura and Mitsugu Akagawa :
Cinnamon extract promotes type I collagen biosynthesis via activation of IGF-I signaling in human dermal fibroblasts.,
Journal of Agricultural and Food Chemistry, Vol.60, No.5, 1193-1200, 2012.- (要約)
- The breakdown of collagenous networks with aging results in hypoactive changes in the skin. Accordingly, reviving stagnant collagen synthesis can help protect dermal homeostasis against aging. We searched for type I collagen biosynthesis-inducing substances in various foods using human dermal fibroblasts and found that cinnamon extract facilitates collagen biosynthesis. Cinnamon extract potently up-regulated both mRNA and protein expression levels of type I collagen without cytotoxicity. We identified cinnamaldehyde as a major active component promoting the expression of collagen by HPLC and NMR analysis. Since insulin-like growth factor-I (IGF-I) is the most potent stimulator of collagen biosynthesis in fibroblasts, we examined the effect of cinnamaldehyde on IGF-I signaling. Treatment with cinnamaldehyde significantly increased the phosphorylation levels of the IGF-I receptor and its downstream signaling molecules such as insulin receptor substrate-1 and Erk1/2 in an IGF-I-independent manner. These results suggested that cinnamon extract is useful in antiaging treatment of skin.
- (キーワード)
- Cell Line / Cinnamomum zeylanicum / Collagen Type I / Fibroblasts / Humans / Insulin-Like Growth Factor I / Plant Extracts / Signal Transduction / Skin
- (出版サイトへのリンク)
- ● Publication site (DOI): 10.1021/jf2043357
- (文献検索サイトへのリンク)
- ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 22233457
- ● Search Scopus @ Elsevier (PMID): 22233457
- ● Search Scopus @ Elsevier (DOI): 10.1021/jf2043357
(DOI: 10.1021/jf2043357, PubMed: 22233457) Chika Wakita, Kazuya Honda, Takahiro Shibata, Mitsugu Akagawa and Koji Uchida :
A method for detection of 4-hydroxy-2-nonenal adducts in proteins.,
Free Radical Biology and Medicine, Vol.51, No.1, 1-4, 2011.- (要約)
- We developed a procedure to measure 4-hydroxy-2-nonenal (HNE)-amino acid adducts using the fluorescent probe 2-aminopyridine (2-AP). The method is based on the fact that HNE forms Michael addition-type amino acid adducts possessing an aldehyde functionality, which upon reaction with 2-AP in the presence of NaBH₃CN can be converted to their pyridylaminated derivatives. The HNE-amino acid adducts, namely Michael addition-type HNE-cysteine, HNE-histidine, and HNE-lysine adducts, after pyridylamination were resistant to conventional acid-hydrolysis conditions for protein (6N HCl/110°C/24 h) and could be detected by HPLC with a fluorescence detector. The reductive amination-based fluorescent labeling of HNE adducts is a simple and accurate technique that may be widely used to reveal increased levels of covalently modified proteins with HNE and its related aldehydes during aging and disease.
- (キーワード)
- Aldehydes / Aminopyridines / Borohydrides / Chemistry Techniques, Analytical / Chromatography, High Pressure Liquid / Proteins / Spectrometry, Fluorescence
- (出版サイトへのリンク)
- ● Publication site (DOI): 10.1016/j.freeradbiomed.2011.02.037
- (文献検索サイトへのリンク)
- ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 21457776
- ● Search Scopus @ Elsevier (PMID): 21457776
- ● Search Scopus @ Elsevier (DOI): 10.1016/j.freeradbiomed.2011.02.037
(DOI: 10.1016/j.freeradbiomed.2011.02.037, PubMed: 21457776) Tomoko Tanaka, Takeshi Ishii, Daisuke Mizuno, Taiki Mori, Ryoichi Yamaji, Yoshimasa Nakamura, Shigenori Kumazawa, Tsutomu Nakayama and Mitsugu Akagawa :
(-)-Epigallocatechin-3-gallate suppresses growth of AZ521 human gastric cancer cells by targeting the DEAD-box RNA helicase p68.,
Free Radical Biology and Medicine, Vol.50, No.10, 1324-1335, 2011.- (要約)
- (-)-Epigallocatechin-3-gallate (EGCG), the most abundant and biologically active polyphenol in green tea, induces apoptosis and suppresses proliferation of cancer cells by modulating multiple signal transduction pathways. However, the fundamental mechanisms responsible for these cancer-preventive effects have not been clearly elucidated. Recently, we found that EGCG can covalently bind to cysteine residues in proteins through autoxidation and subsequently modulate protein function. In this study, we demonstrate the direct binding of EGCG to cellular proteins in AZ521 human gastric cancer cells by redox-cycle staining. We comprehensively explored the binding targets of EGCG from EGCG-treated AZ521 cells by proteomics techniques combined with the boronate-affinity pull-down method. The DEAD-box RNA helicase p68, which is overexpressed in a variety of tumor cells and plays an important role in cancer development and progression, was identified as a novel EGCG-binding target. Exposure of AZ521 cells to EGCG lowered the p68 level dose dependently. The present findings show that EGCG inhibits AZ521 cell proliferation by preventing β-catenin oncogenic signaling through proteasomal degradation of p68 and provide a new perspective on the molecular mechanism of EGCG action.
- (キーワード)
- Antineoplastic Agents / Apoptosis / Catechin / Cell Proliferation / DEAD-box RNA Helicases / Drug Screening Assays, Antitumor / Humans / Molecular Conformation / Stereoisomerism / Stomach Neoplasms / Structure-Activity Relationship / Tumor Cells, Cultured
- (出版サイトへのリンク)
- ● Publication site (DOI): 10.1016/j.freeradbiomed.2011.01.024
- (文献検索サイトへのリンク)
- ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 21277973
- ● Search Scopus @ Elsevier (PMID): 21277973
- ● Search Scopus @ Elsevier (DOI): 10.1016/j.freeradbiomed.2011.01.024
(DOI: 10.1016/j.freeradbiomed.2011.01.024, PubMed: 21277973) Takeshi Ishii, Tatsuya Ichikawa, Kanako Minoda, Koji Kusaka, Sohei Ito, Yukiko Suzuki, Mitsugu Akagawa, Kazuki Mochizuki, Toshinao Goda and Tsutomu Nakayama :
Human serum albumin as an antioxidant in the oxidation of (-)-epigallocatechin gallate: participation of reversible covalent binding for interaction and stabilization.,
Bioscience, Biotechnology, and Biochemistry, Vol.75, No.1, 100-106, 2011.- (要約)
- Human serum albumin (HSA) contributes to the stabilization of (-)-epigallocatechin gallate (EGCg) in serum. We characterize in the present study the mechanisms for preventing EGCg oxidation by HSA. EGCg was stable in human serum or buffers with HSA, but (-)-epigallocatechin (EGC) was unstable. We show by comparing EGCg and EGC in a neutral buffer that EGCg had a higher binding affinity than EGC. This indicates that the galloyl moiety participated in the interaction of EGCg with HSA and that this interaction was of critical importance in preventing EGCg oxidation. The binding affinity of EGCg for HSA and protein carbonyl formation in HSA were enhanced in an alkaline buffer. These results suggest the reversible covalent modification of EGCg via Schiff-base formation, and that the immobilization of EGCg to HSA, through the formation of a stable complex, prevented the polymerization and decomposition of EGCg in human serum.
- (キーワード)
- Aerobiosis / Amination / Antioxidants / Catechin / Humans / Oxidation-Reduction / Protein Binding / Pyrogallol / Serum Albumin / Water
- (出版サイトへのリンク)
- ● Publication site (DOI): 10.1271/bbb.100600
- (文献検索サイトへのリンク)
- ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 21228463
- ● Search Scopus @ Elsevier (PMID): 21228463
- ● Search Scopus @ Elsevier (DOI): 10.1271/bbb.100600
(DOI: 10.1271/bbb.100600, PubMed: 21228463) Taiki Mori, Takeshi Ishii, Mitsugu Akagawa, Yoshimasa Nakamura and Tsutomu Nakayama :
Covalent binding of tea catechins to protein thiols: the relationship between stability and electrophilic reactivity.,
Bioscience, Biotechnology, and Biochemistry, Vol.74, No.12, 2451-2456, 2010.- (要約)
- In this study, we investigated the relationship between the stability of catechins and their electrophilic reactivity with proteins. The stability of catechins was evaluated by HPLC analysis. Catechol-type catechins were stable in a neutral buffer, but pyrogallol-type catechins, such as (-)-epigallocatechin gallate (EGCg), were unstable. The electrophilic reactivity of catechins with thiol groups in a model peptide and a protein was confirmed by both mass spectrometry and electrophoresis/blotting with redox-cycling staining. In a comparison of several catechins, pyrogallol-type catechins had higher reactivity with protein thiols than catechol-type catechins. The instability and reactivity of EGCg were enhanced in an alkaline pH buffer. The reactivity of EGCg was reduced by antioxidants due to their ability to prevent EGCg autoxidation. These results indicate that the instability against oxidation of catechins is profoundly related to their electrophilic reactivity. Consequently, the difference in these properties of tea catechins can contribute to the magnitude of their biological activities.
- (キーワード)
- Catechin / Drug Stability / Electrons / Oxidation-Reduction / Peptides / Proteins / Reactive Oxygen Species / Sulfhydryl Compounds / Tea
- (出版サイトへのリンク)
- ● Publication site (DOI): 10.1271/bbb.100509
- (文献検索サイトへのリンク)
- ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 21150116
- ● Search Scopus @ Elsevier (PMID): 21150116
- ● Search Scopus @ Elsevier (DOI): 10.1271/bbb.100509
(DOI: 10.1271/bbb.100509, PubMed: 21150116) Kentaro Tsuji-Naito, Seiko Ishikura, Mitsugu Akagawa and Hiroshi Saeki :
α-Lipoic acid induces collagen biosynthesis involving prolyl hydroxylase expression via activation of TGF-β-Smad signaling in human dermal fibroblasts.,
Connective Tissue Research, Vol.51, No.5, 378-387, 2010.- (要約)
- The collapse of collagenous networks with aging results in comprehensive changes in the functional properties of skin. α-Lipoic acid (LA) is known to possess beneficial effects against skin aging, effects often presumed to be its antioxidant potential. However, the effects of LA on fibrillogenesis in dermal fibroblasts have not been adequately assessed. In this study, we demonstrated for the first time that LA enhances the biosynthesis of new collagen in normal human dermal fibroblasts (NHDFs). By using a quantitative dye-binding method and immunochemical approaches, we showed that LA effectively increased the expression and subsequently the deposition of type I collagen in NHDFs. LA also facilitated the expression of a collagen-processing enzyme, prolyl-4-hydroxylase, pointing to the existence of a posttranslational mechanism among the LA-mediated effects on collagen synthesis. In addition, we determined that both Smad 2/3 were rapidly phosphorylated by treatment with LA within 30 min, indicating that LA enhances type I collagen synthesis through the activation of Smad signaling. Pretreatment of SB431542, a specific transforming growth factor-β (TGF-β) receptor type I (TβRI) kinase inhibitor, blocked LA-mediated Smad 2/3 phosphorylations and both type I collagen and prolyl-4-hydroxylase expression, suggesting that LA-mediated cell responses are regulated by TβRI kinase-dependent pathway. Levels of TGF-β secretion after 4 hr of treatment with LA were not remarkably elevated, indicating that LA may be able to mimic TGF-β-mediated cell response. The study results produced new insights into the molecular pharmacology of LA in NHDFs, with potential applications in the treatment of aging skin.
- (キーワード)
- Cell Line / Collagen Type I / Dermis / Fibroblasts / Humans / Infant, Newborn / Phosphorylation / Procollagen-Proline Dioxygenase / Protein Processing, Post-Translational / Signal Transduction / Smad Proteins / Smad2 Protein / Thioctic Acid / Transforming Growth Factor beta
- (出版サイトへのリンク)
- ● Publication site (DOI): 10.3109/03008200903486188
- (文献検索サイトへのリンク)
- ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 20604712
- ● Search Scopus @ Elsevier (PMID): 20604712
- ● Search Scopus @ Elsevier (DOI): 10.3109/03008200903486188
(DOI: 10.3109/03008200903486188, PubMed: 20604712) Takeshi Ishii, Taiki Mori, Tatsuya Ichikawa, Maiko Kaku, Koji Kusaka, Yoshinori Uekusa, Mitsugu Akagawa, Yoshiyuki Aihara, Takumi Furuta, Toshiyuki Wakimoto, Toshiyuki Kan and Tsutomu Nakayama :
Structural characteristics of green tea catechins for formation of protein carbonyl in human serum albumin.,
Bioorganic & Medicinal Chemistry, Vol.18, No.14, 4892-4896, 2010.- (要約)
- Catechins are polyphenolic antioxidants found in green tea leaves. Recent studies have reported that various polyphenolic compounds, including catechins, cause protein carbonyl formation in proteins via their pro-oxidant actions. In this study, we evaluate the formation of protein carbonyl in human serum albumin (HSA) by tea catechins and investigate the relationship between catechin chemical structure and its pro-oxidant property. To assess the formation of protein carbonyl in HSA, HSA was incubated with four individual catechins under physiological conditions to generate biotin-LC-hydrazide labeled protein carbonyls. Comparison of catechins using Western blotting revealed that the formation of protein carbonyl in HSA was higher for pyrogallol-type catechins than the corresponding catechol-type catechins. In addition, the formation of protein carbonyl was also found to be higher for the catechins having a galloyl group than the corresponding catechins lacking a galloyl group. The importance of the pyrogallol structural motif in the B-ring and the galloyl group was confirmed using methylated catechins and phenolic acids. These results indicate that the most important structural element contributing to the formation of protein carbonyl in HSA by tea catechins is the pyrogallol structural motif in the B-ring, followed by the galloyl group. The oxidation stability and binding affinity of tea catechins with proteins are responsible for the formation of protein carbonyl, and consequently the difference in these properties of each catechin may contribute to the magnitude of their biological activities.
- (キーワード)
- Catechin / Humans / Molecular Structure / Protein Carbonylation / Pyrogallol / Serum Albumin / Tea
- (出版サイトへのリンク)
- ● Publication site (DOI): 10.1016/j.bmc.2010.06.021
- (文献検索サイトへのリンク)
- ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 20598557
- ● Search Scopus @ Elsevier (PMID): 20598557
- ● Search Scopus @ Elsevier (DOI): 10.1016/j.bmc.2010.06.021
(DOI: 10.1016/j.bmc.2010.06.021, PubMed: 20598557) Takeshi Ishii, Mitsugu Akagawa, Yuji Naito, Osamu Handa, Tomohisa Takagi, Taiki Mori, Shigenori Kumazawa, Toshikazu Yoshikawa and Tsutomu Nakayama :
Pro-oxidant action of pyrroloquinoline quinone: characterization of protein oxidative modifications.,
Bioscience, Biotechnology, and Biochemistry, Vol.74, No.3, 663-666, 2010.- (要約)
- Pyrroloquinoline quinone (PQQ), a putative essential nutrient, is a redox modulator in cell and animal models. Here we characterized PQQ-induced protein oxidative modifications in a model peptide and protein, and we propose that the mechanism of protein modification by PQQ is redox cycling-mediated oxidation. PQQ may contribute to the regulation of intracellular protein functions through its prooxidant action.
- (キーワード)
- Antioxidants / Oxidation-Reduction / Oxidative Stress / PQQ Cofactor / Protein Carbonylation / Proteins / Reactive Oxygen Species
- (出版サイトへのリンク)
- ● Publication site (DOI): 10.1271/bbb.90764
- (文献検索サイトへのリンク)
- ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 20208375
- ● Search Scopus @ Elsevier (PMID): 20208375
- ● Search Scopus @ Elsevier (DOI): 10.1271/bbb.90764
(DOI: 10.1271/bbb.90764, PubMed: 20208375) Takeshi Ishii, Miki Ishikawa, Noriyuki Miyoshi, Mayuko Yasunaga, Mitsugu Akagawa, Koji Uchida and Yoshimasa Nakamura :
Catechol type polyphenol is a potential modifier of protein sulfhydryls: development and application of a new probe for understanding the dietary polyphenol actions.,
Chemical Research in Toxicology, Vol.22, No.10, 1689-1698, 2009.- (要約)
- The oxidation of dietary polyphenols with a catechol structure leads to the formation of an o-quinone structure, which rapidly reacts with sulfhydryls such as glutathione and protein cysteine residues. This modification may be important for understanding the redox regulation of cell functions by polyphenols. In this study, to investigate the catechol modification of protein sulfhydryls, we used 3,4-dihydroxyphenyl acetic acid (DPA) as a model catechol compound and developed a new probe to directly detect protein modification by catechol type polyphenols using a biotinylated DPA (Bio-DPA). The oxidation-dependent electrophilic reactivity of DPA with peptide sulfhydryls was confirmed by both mass spectrometry and nuclear magnetic resonance spectroscopy. When RL34 cells were treated with Bio-DPA, the significant incorporation of Bio-DPA into a 40 kDa protein was observed by Western blot analysis. The band was identified by mass spectrometry as the cytoskeletal protein, beta-actin. This identification was confirmed by the pull-down assay with anti-beta-actin antibody. To examine the reactivity of the catechol type polyphenols, such as flavonoids, to endogenous beta-actin, RL34 cells were coexposed to Bio-DPA and the flavonoids quercetin, (-)-epicatechin, and (-)-epicatechin gallate. Upon exposure of the cells to Bio-DPA in the presence of the flavonoids, we observed a significant decrease in the DPA-modified beta-actin. These results indicate that beta-actin is one of the major targets of protein modification by catechol type polyphenols and that Bio-DPA is an useful probe for understanding the redox regulation by dietary polyphenols. Furthermore, Keap1, a scaffold protein to the actin cytoskeleton controlling cytoprotective enzyme genes, was also identified as another plausible target of the catechol type polyphenols by oxidative modification of the intracellular sulfhydryls. These results provide an alternative approach to understand that catechol type polyphenol is a potential modifier of redox-dependent cellular events through sulfhydryl modification.
- (キーワード)
- 3,4-Dihydroxyphenylacetic Acid / Actins / Amino Acid Sequence / Animals / Biotinylation / Catechols / Cell Line / Flavonoids / Glutathione / Intracellular Signaling Peptides and Proteins / Kelch-Like ECH-Associated Protein 1 / Magnetic Resonance Spectroscopy / Mass Spectrometry / Oxidation-Reduction / Peptides / Phenols / Polyphenols / Proteins / Rats / Sulfhydryl Compounds
- (出版サイトへのリンク)
- ● Publication site (DOI): 10.1021/tx900148k
- (文献検索サイトへのリンク)
- ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 19743802
- ● Search Scopus @ Elsevier (PMID): 19743802
- ● Search Scopus @ Elsevier (DOI): 10.1021/tx900148k
(DOI: 10.1021/tx900148k, PubMed: 19743802) Chika Wakita, Takuya Maeshima, Atsushi Yamazaki, Takahiro Shibata, Sohei Ito, Mitsugu Akagawa, Makoto Ojika, Junji Yodoi and Koji Uchida :
Stereochemical configuration of 4-hydroxy-2-nonenal-cysteine adducts and their stereoselective formation in a redox-regulated protein.,
The Journal of Biological Chemistry, Vol.284, No.42, 28810-28822, 2009.- (要約)
- 4-Hydroxy-2-nonenal (HNE), a major racemic product of lipid peroxidation, preferentially reacts with cysteine residues to form a stable HNE-cysteine Michael addition adduct possessing three chiral centers. Here, to gain more insight into sulfhydryl modification by HNE, we characterized the stereochemical configuration of the HNE-cysteine adducts and investigated their stereoselective formation in redox-regulated proteins. To characterize the HNE-cysteine adducts by NMR, the authentic (R)-HNE- and (S)-HNE-cysteine adducts were prepared by incubating N-acetylcysteine with each HNE enantiomer, both of which provided two peaks in reversed-phase high performance liquid chromatography (HPLC). The NMR analysis revealed that each peak was a mixture of anomeric isomers. In addition, mutarotation at the anomeric center was also observed in the analysis of the nuclear Overhauser effect. To analyze these adducts in proteins, we adapted a pyridylamination-based approach, using 2-aminopyridine in the presence of sodium cyanoborohydride, which enabled analyzing the individual (R)-HNE- and (S)-HNE-cysteine adducts by reversed-phase HPLC following acid hydrolysis. Using the pyridylamination method along with mass spectrometry, we characterized the stereoselective formation of the HNE-cysteine adducts in human thioredoxin and found that HNE preferentially modifies Cys(73) and, to the lesser extent, the active site Cys(32). More interestingly, the (R)-HNE- and (S)-HNE-cysteine adducts were almost equally formed at Cys(73), whereas Cys(32) exhibited a remarkable preference for the adduct formation with (R)-HNE. Finally, the utility of the method for the determination of the HNE-cysteine adducts was confirmed by an in vitro study using HeLa cells. The present results not only offer structural insight into sulfhydryl modification by lipid peroxidation products but also provide a platform for the chemical analysis of protein S-associated aldehydes in vitro and in vivo.
- (キーワード)
- Aldehydes / Borohydrides / Chromatography, High Pressure Liquid / Cysteine / HeLa Cells / Humans / Lipid Peroxidation / Magnetic Resonance Spectroscopy / Mass Spectrometry / Models, Chemical / Oxidation-Reduction / Peptides / Proteins / Recombinant Proteins / Stereoisomerism
- (出版サイトへのリンク)
- ● Publication site (DOI): 10.1074/jbc.M109.019927
- (文献検索サイトへのリンク)
- ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 19692331
- ● Search Scopus @ Elsevier (PMID): 19692331
- ● Search Scopus @ Elsevier (DOI): 10.1074/jbc.M109.019927
(DOI: 10.1074/jbc.M109.019927, PubMed: 19692331) Mitsugu Akagawa, Kyozo Suyama and Koji Uchida :
Fluorescent detection of alpha-aminoadipic and gamma-glutamic semialdehydes in oxidized proteins.,
Free Radical Biology and Medicine, Vol.46, No.6, 701-706, 2008.- (要約)
- The oxidative modification of proteins is believed to play a critical role in the etiology and/or progression of several diseases. alpha-Aminoadipic semialdehyde (AAS) and gamma-glutamic semialdehyde (GGS) residues represent major oxidized amino acids generated in oxidized proteins. This paper describes a novel procedure for the specific and sensitive determination of AAS and GGS after their reductive amination with sodium cyanoborohydride and p-aminobenzoic acid, a fluorescence reagent, to their corresponding derivatives, followed by a high-performance liquid chromatography (HPLC) analysis. This fluorescent labeling of protein-associated aldehyde moieties is a simple and accurate technique that may be widely used to reveal increased levels of oxidatively modified proteins with reactive oxygen species during aging and disease.
- (キーワード)
- 2-Aminoadipic Acid / 4-Aminobenzoic Acid / Adipates / Biochemistry / Borohydrides / Chromatography, High Pressure Liquid / Fluorescent Dyes / Glutamates / Glutamic Acid / Oxidation-Reduction / Protein Binding / Protein Processing, Post-Translational / Reactive Oxygen Species / Sensitivity and Specificity
- (出版サイトへのリンク)
- ● Publication site (DOI): 10.1016/j.freeradbiomed.2008.12.014
- (文献検索サイトへのリンク)
- ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 19135526
- ● Search Scopus @ Elsevier (PMID): 19135526
- ● Search Scopus @ Elsevier (DOI): 10.1016/j.freeradbiomed.2008.12.014
(DOI: 10.1016/j.freeradbiomed.2008.12.014, PubMed: 19135526) Takeshi Ishii, Taiki Mori, Tomoko Tanaka, Daisuke Mizuno, Ryoichi Yamaji, Shigenori Kumazawa, Tsutomu Nakayama and Mitsugu Akagawa :
Covalent modification of proteins by green tea polyphenol (-)-epigallocatechin-3-gallate through autoxidation.,
Free Radical Biology and Medicine, Vol.45, No.10, 1384-1394, 2008.- (要約)
- Green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) has various beneficial properties including chemopreventive, anticarcinogenic, and antioxidant actions. The interaction with proteins known as EGCG-binding targets may be related to the anticancer effects. However, the binding mechanisms for this activity remain poorly understood. Using mass spectrometry and chemical detection methods, we found that EGCG forms covalent adducts with cysteinyl thiol residues in proteins through autoxidation. To investigate the functional modulation caused by binding of EGCG, we examined the interaction between EGCG and a thiol enzyme, glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Concentration-dependent covalent binding of EGCG to GAPDH was found to be coupled to the irreversible inhibition of GAPDH activity. Mutation experiments revealed that EGCG is primarily bound to the cysteinyl thiol group of the active center, indicating that the irreversible inhibition of GAPDH is due to the covalent attachment of EGCG to the active-center cysteine. Moreover, using EGCG-treated cancer cells, we identified GAPDH as a target of EGCG covalent binding through specific interactions between catechols and aminophenyl boronate agarose resin. Based on these findings, we propose that the covalent modification of proteins by EGCG may be a novel pathway related to the biological activity of EGCG.
- (キーワード)
- Antineoplastic Agents / Antioxidants / Binding Sites / Catechin / Cell Survival / Cysteine / Drug Screening Assays, Antitumor / Glyceraldehyde-3-Phosphate Dehydrogenases / Humans / Molecular Conformation / Oxidation-Reduction / Tea / Tumor Cells, Cultured
- (出版サイトへのリンク)
- ● Publication site (DOI): 10.1016/j.freeradbiomed.2008.07.023
- (文献検索サイトへのリンク)
- ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 18771724
- ● Search Scopus @ Elsevier (PMID): 18771724
- ● Search Scopus @ Elsevier (DOI): 10.1016/j.freeradbiomed.2008.07.023
(DOI: 10.1016/j.freeradbiomed.2008.07.023, PubMed: 18771724) Ishii Takeshi, Mori Taiki, Kumazawa Shigenori, Nakayama Tsutomu and Mitsugu Akagawa :
Protein oxidative modification with pyrroloquinoline quinone,
Journal of Clinical Biochemistry and Nutrition, Vol.43, No.S1, 571-574, 2008. Mori Taiki, Wakabayashi Miyuki, Ishii Takeshi, Mitsugu Akagawa and Nakayama Tsutomu :
Mass spectrometry-based study of protein redox modification by alpha-lipoic acid,
Journal of Clinical Biochemistry and Nutrition, Vol.43, No.S1, 456-459, 2008. Handoyo Tri, Mitsugu Akagawa, Morita Naofumi, Maeda Tomoko and Mitsunaga Toshio :
Hypoallergenic characteristics of wheat flour produced by stepwise polishing,
International Journal of Food Properties, Vol.11, No.2, 243-252, 2008. Naznin Tahera Most, Mitsugu Akagawa, Okugawa Kayo, Maeda Tomoko and Morita Naofumi :
Characterization of E- and Z-ajoene obtained from different varieties of garlics,
Food Chemistry, Vol.106, No.3, 1113-1119, 2008. Kyozo Suyama, Miyako Yoshioka, Mitsugu Akagawa, Yuichi Murayama, Hiroko Horii, Masuhiro Takata, Takashi Yokoyama and Shirou Mohri :
Assessment of prion inactivation by fenton reaction using protein misfolding cyclic amplification and bioassay.,
Bioscience, Biotechnology, and Biochemistry, Vol.71, No.8, 2069-2071, 2007.- (要約)
- An abnormal isoform of the prion protein, associated with transmissible spongiform encephalopathies, retains infectivity even after undergoing routine sterilization processes. We found that a formulation of iron ions combined with hydrogen peroxide effectively reduced infectivity and the level of abnormal isoforms of the prion protein in scrapie-infected brain homogenates. Therefore, the Fenton reaction has potential for prion decontamination.
- (キーワード)
- Animals / Brain / Cricetinae / Hydrogen Peroxide / Iron / Prion Diseases / Prions / Protein Denaturation / Protein Folding / Protein Isoforms / Scrapie / Sterilization
- (出版サイトへのリンク)
- ● Publication site (DOI): 10.1271/bbb.70085
- (文献検索サイトへのリンク)
- ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 17690456
- ● Search Scopus @ Elsevier (PMID): 17690456
- ● Search Scopus @ Elsevier (DOI): 10.1271/bbb.70085
(DOI: 10.1271/bbb.70085, PubMed: 17690456) Mitsugu Akagawa, Tri Handoyo, Takeshi Ishii, Shigenori Kumazawa, Naofumi Morita and Kyozo Suyama :
Proteomic analysis of wheat flour allergens.,
Journal of Agricultural and Food Chemistry, Vol.55, No.17, 6863-6870, 2007.- (要約)
- Wheat can cause severe IgE-mediated systematic reactions, but knowledge on relevant wheat allergens at the molecular level is scanty. The aim of the present study was to achieve a more detailed and comprehensive characterization of the wheat allergens involved in food allergy to wheat using proteomic strategies, referred to as "allergenomics". Whole flour proteins were separated by two-dimensional gel electrophoresis with isoelectric focusing and lithium dodecyl sulfate-polyacrylamide gel electrophoresis. Then, IgE-binding proteins were detected by immunoblotting with sera of patients with a food allergy to wheat. After tryptic digestion, the peptides of IgE-binding proteins were analyzed by matrix-assisted laser desorption ionization tandem time-of-flight mass spectrometry. In this study, we identified four previously reported wheat allergens or their sequentially homologous proteins [serpin, alpha-amylase inhibitor, gamma-gliadin, and low molecular weight (LMW) glutenin] by a database search. As a result of the high resolution of two-dimensional gel electrophoresis, nine subunits of LMW glutenins were identified as the most predominant IgE-binding antigens. The two-dimensional allergen map can be beneficial in many ways. It could be used, for example, for precise diagnosis of wheat-allergic patients and assessment of wheat allergens in food. Additionally, we compared allergenomics to conventional biochemical methods and evaluated the usefulness of a proteomic strategy for identifying putative allergens to wheat allergy.
- (キーワード)
- Allergens / Amino Acid Sequence / Blood Proteins / Flour / Glutens / Humans / Immunoglobulin E / Molecular Sequence Data / Plant Proteins / Proteomics / Triticum / Wheat Hypersensitivity
- (出版サイトへのリンク)
- ● Publication site (DOI): 10.1021/jf070843a
- (文献検索サイトへのリンク)
- ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 17655322
- ● Search Scopus @ Elsevier (PMID): 17655322
- ● Search Scopus @ Elsevier (DOI): 10.1021/jf070843a
(DOI: 10.1021/jf070843a, PubMed: 17655322) Kazuyo Toyoda, Ritsuko Nagae, Mitsugu Akagawa, Kosuke Ishino, Takahiro Shibata, Sohei Ito, Noriyuki Shibata, Tomoko Yamamoto, Makio Kobayashi, Yoshinari Takasaki, Tsukasa Matsuda and Koji Uchida :
Protein-bound 4-hydroxy-2-nonenal: an endogenous triggering antigen of antI-DNA response.,
The Journal of Biological Chemistry, Vol.282, No.35, 25769-25778, 2007.- (要約)
- Several lines of evidence indicate that the nonenzymatic oxidative modification of proteins and the subsequent accumulation of the modified proteins have been found in cells during aging and oxidative stress and in various pathological states, including premature diseases, muscular dystrophy, rheumatoid arthritis, and atherosclerosis. Our previous work suggested the existence of molecular mimicry between antibodies raised against hydroxy-2-nonenal (HNE)-modified protein and anti-DNA autoantibodies, a serologic hallmark of systemic lupus erythematosus (SLE). In the present study, we investigated the possible involvement of HNE-modified proteins as the endogenous source of the anti-DNA antibodies. Accumulation of the antigen recognized by the antibody against the HNE-modified protein was observed in the nucleus of almost all of the epidermal cells from patients with autoimmune diseases, including SLE. The SLE patients also showed significantly higher serum levels of the anti-HNE titer than healthy individuals. To determine if a specific anti-DNA response could be initiated by the HNE-derived epitopes, we immunized BALB/c mice with the HNE-modified protein and observed a progressive increase in the anti-DNA response. Moreover, we generated the monoclonal antibodies, showing recognition specificity toward DNA, and found that they can bind to two structurally distinct antigens (i.e. the native DNA and protein-bound 4-oxo-2-nonenal). The findings in this study provide evidence to suspect an etiologic role for lipid peroxidation in autoimmune diseases.
- (キーワード)
- Aldehydes / Animals / Antibodies, Antinuclear / Arthritis, Rheumatoid / Atherosclerosis / Autoantigens / Cattle / Cellular Senescence / Epitopes / Female / Humans / Lipid Peroxidation / Lupus Erythematosus, Systemic / Mice / Mice, Inbred BALB C / Molecular Mimicry / Muscular Dystrophies / Oxidation-Reduction / Oxidative Stress / Protein Processing, Post-Translational / Serum Albumin, Bovine
- (出版サイトへのリンク)
- ● Publication site (DOI): 10.1074/jbc.M703039200
- (文献検索サイトへのリンク)
- ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 17588942
- ● Search Scopus @ Elsevier (PMID): 17588942
- ● Search Scopus @ Elsevier (DOI): 10.1074/jbc.M703039200
(DOI: 10.1074/jbc.M703039200, PubMed: 17588942) Kyozo Suyama, Miyako Yoshioka, Mitsugu Akagawa, Yuichi Murayama, Hiroko Horii, Masuhiro Takata, Takashi Yokoyama and Shirou Mohri :
Prion inactivation by the Maillard reaction.,
Biochemical and Biophysical Research Communications, Vol.356, No.1, 245-248, 2007.- (要約)
- Since variant Creutzfeldt-Jakob disease (vCJD) has been suspected to be attributable to the infectious agents associated with bovine spongiform encephalopathy (BSE), it is important to prevent the transmission of pathogenic forms of prion protein (PrP(Sc)) through contaminated feeding materials such as meat and bone meal (MBM). Here, we demonstrate that the Maillard reaction employing a formulation of glucose in combination with sodium hydrogen carbonates effectively reduced the infectivity (approximately 5.9-log reduction) of a scrapie-infected hamster brain homogenate. In addition to a bioassay, a protein misfolding cyclic amplification (PMCA) technique, in which PrP(Sc) can be amplified in vitro, was used as a rapid test for assessing PrP(Sc) inactivation. The PMCA analysis also indicated that the PrP(Sc) level in the infected material significantly decreased following the Maillard reaction. Therefore, the Maillard reaction can be employed for the decontamination of large amounts of byproducts such as MBM.
- (キーワード)
- Animals / Blotting, Western / Brain / Cricetinae / Maillard Reaction / Mice / PrPSc Proteins / Prion Diseases / Survival Rate
- (出版サイトへのリンク)
- ● Publication site (DOI): 10.1016/j.bbrc.2007.02.113
- (文献検索サイトへのリンク)
- ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 17336934
- ● Search Scopus @ Elsevier (PMID): 17336934
- ● Search Scopus @ Elsevier (DOI): 10.1016/j.bbrc.2007.02.113
(DOI: 10.1016/j.bbrc.2007.02.113, PubMed: 17336934) Mitsugu Akagawa, Yoshihisa Ishii, Takeshi Ishii, Takahiro Shibata, Mari Yotsu-Yamashita, Kyozo Suyama and Koji Uchida :
Metal-catalyzed oxidation of protein-bound dopamine.,
Biochemistry, Vol.45, No.50, 15120-15128, 2006.- (要約)
- Dopamine (DA) is an unstable neurotransmitter that readily oxidizes to the DA quinone and forms reactive oxygen species, such as superoxide and hydrogen peroxide. The oxidized dopamine also forms thiol conjugates with sulfhydryl groups on cysteine, glutathione, and proteins. In the present study, we determined the redox potential of the protein-bound DA and established a novel mechanism for the oxidative modification of the protein, in which the DA-cysteine adduct generated in the DA-modified protein causes oxidative modification of the DA-bound protein in the presence of Cu2+. Exposure of a sulfhydryl enzyme, glyceraldehyde-3-phosphate dehydrogenase, to DA resulted in a significant loss of sulfhydryl groups and the formation of the DA-cysteine adduct. When the DA-modified protein was incubated with Cu2+, we observed aggregation and degradation of the DA-bound protein and concomitant formation of a protein carbonyl, a marker of an oxidatively modified protein. Furthermore, we analyzed the carbonyl products generated during the Cu2+-catalyzed oxidation of the DA-modified protein and revealed the production of glutamic and aminoadipic semialdehydes, consisting of the protein carbonyls generated. The cysteinyl-DA residue generated in the DA-modified protein was suggested to represent a redox-active adduct, based on the observations that the cysteinyl-DA adduct, 5-S-cysteinyldopamine, produced by the reaction of cysteine with DA, gave rise to the oxidative modification of bovine serum albumin in the presence of Cu2+. These data suggest that the DA-modified protein may be involved in redox alteration under oxidative stress, whereby DA covalently binds to cysteine residues, generating the redox-active cysteinyl-DA adduct that causes the metal-catalyzed oxidation of protein.
- (キーワード)
- Animals / Catalysis / Cattle / Cell Line / Copper / Cysteine / Dopamine / Glyceraldehyde-3-Phosphate Dehydrogenases / Oxidation-Reduction / Reactive Oxygen Species / Serum Albumin, Bovine
- (出版サイトへのリンク)
- ● Publication site (DOI): 10.1021/bi0614434
- (文献検索サイトへのリンク)
- ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 17154550
- ● Search Scopus @ Elsevier (PMID): 17154550
- ● Search Scopus @ Elsevier (DOI): 10.1021/bi0614434
(DOI: 10.1021/bi0614434, PubMed: 17154550) Mitsugu Akagawa, Daisuke Sasaki, Yoshihisa Ishii, Yayoi Kurota, Mari Yotsu-Yamashita, Koji Uchida and Kyozo Suyama :
New method for the quantitative determination of major protein carbonyls, alpha-aminoadipic and gamma-glutamic semialdehydes: investigation of the formation mechanism and chemical nature in vitro and in vivo.,
Chemical Research in Toxicology, Vol.19, No.8, 1059-1065, 2006.- (要約)
- Alpha-aminoadipic semialdehyde (AAS) and gamma-glutamic semialdehyde (GGS) are identified as the major carbonyl products in oxidized proteins. To elucidate the formation pathway of AAS and GGS in vivo, we developed and validated a new quantification method. AAS and GGS in proteins were derivatized by reductive amination with NaCNBH(3) and p-aminobenzoic acid, a fluorescent reagent, followed by acid hydrolysis. It is noteworthy that the fluorescent derivatives were completely stable during acid hydrolysis. The present method permitted the specific, accurate, and sensitive quantification of both semialdehydes by fluorometric high-performance liquid chromatography. Analysis of proteins oxidized by various oxidation systems revealed that AAS and GGS are notably generated by the reaction of proteins with (*)OH, which is produced by metal-catalyzed oxidation (MCO). Furthermore, exposure of transferrin and human plasma to ascorbic acid and H(2)O(2) significantly promoted the formation of AAS and GGS in vitro, suggesting that both semialdehydes can be generated by MCO in vivo. We also demonstrated their generation through oxidative stress induced by acute iron overload in vivo. In this paper, we describe this analytical technique for simple and precise measurement of AAS and GGS and discuss their formation mechanism in vivo.
- (キーワード)
- 2-Aminoadipic Acid / Animals / Ascorbic Acid / Blood Proteins / Cattle / Chromatography, High Pressure Liquid / Glutamates / Humans / Hydrogen Peroxide / In Vitro Techniques / Male / Mice / Mice, Inbred Strains / Oxidation-Reduction / Protein Carbonylation / Rats / Transferrin
- (出版サイトへのリンク)
- ● Publication site (DOI): 10.1021/tx060026p
- (文献検索サイトへのリンク)
- ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16918245
- ● Search Scopus @ Elsevier (PMID): 16918245
- ● Search Scopus @ Elsevier (DOI): 10.1021/tx060026p
(DOI: 10.1021/tx060026p, PubMed: 16918245) Mitsugu Akagawa, Sohei Ito, Kazuo Toyoda, Yoshihisa Ishii, Emi Tatsuda, Takahiro Shibata, Satoru Yamaguchi, Yoshichika Kawai, Kousuke Ishino, Yusuke Kishi, Takahiro Adachi, Takeshi Tsubata, Yoshinari Takasaki, Nobutaka Hattori, Tsukasa Matsuda and Uchida Koji :
Bispecific abs against modified protein and DNA with oxidized lipids,
Proceedings of the National Academy of Sciences of the United States of America, Vol.103, No.16, 6160-6165, 2006.- (要約)
- 4-Hydroxy-2-nonenal (HNE), a racemic mixture of 4R- and 4S-enantiomers, is a major product of lipid peroxidation and is believed to be largely responsible for the cytopathological effects observed during oxidative stress. HNE reacts with histidine to form a stable HNE-histidine Michael addition-type adduct possessing three chiral centers in the cyclic hemiacetal structure. We have previously raised the mAbs, anti-R mAb 310 and anti-S mAb S412, that enantioselectively recognized the R-HNE-histidine and R-HNE-histidine adducts, respectively, and demonstrated the presence of both epitopes in vivo. In the present study, to further investigate the anti-HNE immune response, we analyzed the variable genes and primary structure of these Abs and found that the sequence of R310 was highly homologous to anti-DNA autoantibodies, the hallmark of systemic lupus erythematosus. An x-ray crystallographic analysis of the R310 Fab fragment showed that the R-HNE-histidine adduct binds to a hydrophobic pocket in the antigen-binding site. Despite the structural identity to the anti-DNA autoantibodies, however, R310 showed only a slight crossreactivity with the native double-stranded DNA, whereas the Ab immunoreactivity was dramatically enhanced by the treatment of the DNA with 4-oxo-2-nonenal (ONE), an analog of HNE. Moreover, the 7-(2-oxo-heptyl)-substituted 1,N2-etheno-type ONE-2'-deoxynucleoside adducts were identified as alternative epitopes of R310. Molecular mimicry between the R-HNE-histidine configurational isomers and the ONE-DNA base adducts is proposed for the dual crossreactivity.
- (キーワード)
- Aldehydes / Amino Acid Sequence / Animals / Antibodies, Antinuclear / Antibodies, Bispecific / Antibodies, Monoclonal / Autoantibodies / Cross Reactions / Crystallography, X-Ray / DNA / DNA Adducts / Deoxyribonucleosides / Epitopes / Immunoglobulin Fab Fragments / Lipid Peroxidation / Lipids / Lupus Erythematosus, Systemic / Mice / Molecular Mimicry / Molecular Sequence Data / Oxidation-Reduction / Proteins
- (出版サイトへのリンク)
- ● Publication site (DOI): 10.1073/pnas.0600865103
- (文献検索サイトへのリンク)
- ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16603628
- ● Search Scopus @ Elsevier (PMID): 16603628
- ● Search Scopus @ Elsevier (DOI): 10.1073/pnas.0600865103
(DOI: 10.1073/pnas.0600865103, PubMed: 16603628) Mitsugu Akagawa, Tomoko Shigemitsu and Kyozo Suyama :
Oxidative deamination of benzylamine and lysine residue in bovine serum albumin by green tea, black tea, and coffee.,
Journal of Agricultural and Food Chemistry, Vol.53, No.20, 8019-8024, 2005.- (要約)
- Oxidative deamination by various polyphenolic compounds is presumed to be due to the oxidative conversion of polyphenols to the corresponding quinones through autoxidation. Here we examined the oxidative deamination by the polyphenol-rich beverages green tea, black tea, and coffee at a physiological pH and temperature. Green tea, black tea, and coffee extracts oxidatively deaminated benzylamine and the lysine residues of bovine serum albumin to benzaldehyde and alpha-aminoadipic delta-semialdehyde residues, respectively, in sodium phosphate buffer (pH 7.4) at 37 degrees C in both the presence and absence of Cu2+, indicating the occurrence of an amine (lysyl) oxidase-like reaction. We also examined the effects of pH and metal ions on the reaction. The possible biological effects of drinking polyphenol-rich beverages on human are also discussed.
- (キーワード)
- Benzylamines / Coffee / Copper / Deamination / Flavonoids / Hydrogen-Ion Concentration / Lysine / Oxidation-Reduction / Phenols / Polyphenols / Serum Albumin, Bovine / Tea
- (出版サイトへのリンク)
- ● Publication site (DOI): 10.1021/jf050843f
- (文献検索サイトへのリンク)
- ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16190665
- ● Search Scopus @ Elsevier (PMID): 16190665
- ● Search Scopus @ Elsevier (DOI): 10.1021/jf050843f
(DOI: 10.1021/jf050843f, PubMed: 16190665) Mitsugu Akagawa, Daisuke Sasaki, Yayoi Kurota and Kyozo Suyama :
Formation of alpha-aminoadipic and gamma-glutamic semialdehydes in proteins by the Maillard reaction,
Annals of the New York Academy of Sciences, Vol.1043, 129-134, 2005.- (要約)
- Recent research has demonstrated that nonenzymatic glycation (the Maillard reaction) lead to the formation of carbonyl groups and advanced glycation end products (AGEs) in proteins. Such oxidative modifications are a major contributing factor to diabetic complications and aging. alpha-Aminoadipic semialdehyde (AAS) and gamma-glutamic semialdehyde (GGS) have been identified as the major carbonyl products in oxidized proteins both in vitro and in vivo. AAS is an oxidative deamination product of lysine residue, while GGS originates from arginine and proline residues. To evaluate oxidative damage to proteins by the Maillard reaction, we developed a method of detecting AAS and GGS by high-performance liquid chromatography (HPLC). The aldehydic residues in proteins were derivatized by reductive amination with NaCNBH3 and p-aminobenzoic acid (ABA), a fluorescence regent. After acid hydrolysis of the ABA-derivatized protein, ABA-AAS and ABA-GGS were measured by fluorometric HPLC. Thus, AAS and GGS could be detected in various proteins such as human plasma protein using the present method. Accumulation of both aldehydic residues was observed in oxidized proteins by reactive oxygen species. Furthermore, AAS and GGS were markedly formed in the incubation of BSA with ascorbic acid. The formation of both aldehydic residues was also observed in the incubation of BSA with 100 mM glucose or 1.0 mM methylglyoxal in the absence and presence of 100 microM Fe3+ for 2 weeks. These results suggest that the Maillard reaction can contribute to the formation of AAS and GGS in vivo.
- (キーワード)
- 2-Aminoadipic Acid / Amidines / Carcinogens / Glutamates / Glycation End Products, Advanced / Humans / Maillard Reaction / Mutagens / Proteins / Serum Albumin / Serum Albumin, Bovine
- (出版サイトへのリンク)
- ● Publication site (DOI): 10.1196/annals.1333.016
- (文献検索サイトへのリンク)
- ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16037231
- ● Search Scopus @ Elsevier (PMID): 16037231
- ● Search Scopus @ Elsevier (DOI): 10.1196/annals.1333.016
(DOI: 10.1196/annals.1333.016, PubMed: 16037231) Mitsugu Akagawa, Tomoko Shigemitsu and Kyozo Suyama :
Production of hydrogen peroxide by polyphenols and polyphenol-rich beverages under quasi-physiological conditions.,
Bioscience, Biotechnology, and Biochemistry, Vol.67, No.12, 2632-2640, 2003.- (要約)
- To investigate the ability of the production of H(2)O(2) by polyphenols, we incubated various phenolic compounds and natural polyphenols under a quasi-physiological pH and temperature (pH 7.4, 37 degrees C), and then measured the formation of H(2)O(2) by the ferrous ion oxidation-xylenol orange assay. Pyrocatechol, hydroquinone, pyrogallol, 1,2,4-benzenetriol, and polyphenols such as catechins yielded a significant amount of H(2)O(2). We also examined the effects of a metal chelator, pH, and O(2) on the H(2)O(2)-generating property, and the generation of H(2)O(2) by the polyphenol-rich beverages, green tea, black tea, and coffee, was determined. The features of the H(2)O(2)-generating property of green tea, black tea, and coffee were in good agreement with that of phenolic compounds, suggesting that polyphenols are responsible for the generation of H(2)O(2) in beverages. From the results, the possible significances of the H(2)O(2)-generating property of polyphenols for biological systems are discussed.
- (キーワード)
- Antioxidants / Catechols / Chelating Agents / Coffee / Flavonoids / Hydrogen Peroxide / Hydrogen-Ion Concentration / Phenols / Polyphenols / Tea
- (出版サイトへのリンク)
- ● Publication site (DOI): 10.1271/bbb.67.2632
- (文献検索サイトへのリンク)
- ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 14730143
- ● Search Scopus @ Elsevier (PMID): 14730143
- ● Search Scopus @ Elsevier (DOI): 10.1271/bbb.67.2632
(DOI: 10.1271/bbb.67.2632, PubMed: 14730143) Mitsugu Akagawa, Takeshi Sasaki and Kyozo Suyama :
Oxidative deamination of benzylamine by glycoxidation.,
Bioorganic & Medicinal Chemistry, Vol.11, No.7, 1411-1417, 2003.- (要約)
- In the present study, model reactions for the oxidative deamination by glycoxidation using benzylamine were undertaken to elucidate the detail of the reaction. Glucose, 3-deoxyglucosone (3-DG), and methylglyoxal (MG) oxidatively deaminated benzylamine to benzaldehyde in the presence of Cu(2+) at a physiological pH and temperature but not glyoxal. 3-DG and MG were more effective oxidants than glucose. We have determined the effects of metal ions, pH, oxygen, and radical scavengers on the oxidative deamination. The formation of benzaldehyde was greatest with Cu(2+), and was accelerated at a higher pH and in the presence of oxygen. EDTA, catalase, and dimethyl sulfoxide significantly inhibited the oxidation, suggesting the participation of reactive oxygen species. From these results, we propose a mechanism for the oxidative deamination by the Strecker-type reaction and the reactive oxygen species-mediated oxidation during glycoxidation.
- (キーワード)
- Benzaldehydes / Benzylamines / Chelating Agents / Copper / Deamination / Deoxyglucose / Edetic Acid / Free Radical Scavengers / Glucose / Glucose Oxidase / Hydrogen-Ion Concentration / Hydroxyl Radical / Kinetics / Metals / Nitrogen / Oxidation-Reduction / Oxygen / Pyruvaldehyde / Reactive Oxygen Species
- (出版サイトへのリンク)
- ● Publication site (DOI): 10.1016/s0968-0896(02)00584-9
- (文献検索サイトへのリンク)
- ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 12628667
- ● Search Scopus @ Elsevier (PMID): 12628667
- ● Search Scopus @ Elsevier (DOI): 10.1016/s0968-0896(02)00584-9
(DOI: 10.1016/s0968-0896(02)00584-9, PubMed: 12628667) Mitsugu Akagawa, Takeshi Sasaki and Kyozo Suyama :
Oxidative deamination of lysine residue in plasma protein of diabetic rats. Novel mechanism via the Maillard reaction.,
European Journal of Biochemistry, Vol.269, No.22, 5451-5458, 2002.- (要約)
- The levels of alpha-aminoadipic-delta-semialdehyde residue, the oxidative deamination product of lysine residue, in plasma protein from streptozotocin-induced diabetic rats were evaluated. alpha-Aminoadipic-delta-semialdehyde was converted to a bisphenol derivative by acid hydrolysis in the presence of phenol, and determined by high performance liquid chromatography. Analysis of plasma proteins revealed three times higher levels of alpha-aminoadipic-delta-semialdehyde in diabetic subjects compared with normal controls. Furthermore, we explored the oxidative deamination via the Maillard reaction and demonstrated that the lysine residue of bovine serum albumin is oxidatively deaminated during the incubation with various carbohydrates in the presence of Cu2+ at a physiological pH and temperature. This experiment showed that 3-deoxyglucosone and methylglyoxal are the most efficient oxidants of the lysine residue. When the reaction was initiated from glucose, a significant amount of alpha-aminoadipic-delta-semialdehyde was also formed in the presence of Cu2+. The reaction was significantly inhibited by deoxygenation, catalase, and a hydroxyl radical scavenger. The mechanism we propose for the oxidative deamination is the Strecker-type reaction and the reactive oxygen species-mediated oxidation. Based on these findings, we propose a novel mechanism for the oxidative modification of proteins in diabetes, namely the oxidative deamination of the lysine residue via the Maillard reaction.
- (キーワード)
- 2-Aminoadipic Acid / Animals / Blood Proteins / Carbohydrate Metabolism / Chromatography, High Pressure Liquid / Copper / Diabetes Mellitus, Experimental / Hydrogen-Ion Concentration / Hydrolysis / Lysine / Maillard Reaction / Male / Models, Chemical / Oxidation-Reduction / Oxygen / Pyruvaldehyde / Rats / Rats, Wistar / Reactive Oxygen Species / Streptozocin / Temperature / Time Factors
- (出版サイトへのリンク)
- ● Publication site (DOI): 10.1046/j.1432-1033.2002.03243.x
- (文献検索サイトへのリンク)
- ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 12423343
- ● Search Scopus @ Elsevier (PMID): 12423343
- ● Search Scopus @ Elsevier (DOI): 10.1046/j.1432-1033.2002.03243.x
(DOI: 10.1046/j.1432-1033.2002.03243.x, PubMed: 12423343) Mitsugu Akagawa and Kyozo Suyama :
Oxidative deamination by hydrogen peroxide in the presence of metals.,
Free Radical Research, Vol.36, No.1, 13-21, 2002.- (要約)
- Various amines, including lysine residue of bovine serum albumin, were oxidatively deaminated to form the corresponding aldehydes by a H2O2/Cu2+ oxidation system at physiological pH and temperature. The resulting aldehydes were measured by high-performance liquid chromatography. We investigated the effects of metal ions, pH, inhibitors, and O2 on the oxidative deamination of benzylamine by H202. The formation of benzaldehyde was the greatest with Cu2+, and catalysis occurred with Co2+, VO2+, and Fe3+. The reaction was greatly accelerated as the pH value rose and was markedly inhibited by EDTA and catalase. Dimethyl sulfoxide and thiourea, which are hydroxyl radical scavengers, were also effective in inhibiting the generation of benzaldehyde, indicating that the reaction is a hydroxyl radical-mediated reaction. Superoxide dismutase greatly stimulated the reaction, probably due to the formation of hydroxyl radicals. O2 was not required in the oxidation, and instead slightly inhibited the reaction. We also examined several oxidation systems. Ascorbic acid/O2/Cu2+ and hemoglobin/H2O2 systems also converted benzylamine to benzaldehyde. The proposed mechanism of the oxidative deamination by H2O2/Cu2+ system is discussed.
- (キーワード)
- Benzaldehydes / Benzylamines / Catalase / Catalysis / Cobalt / Copper / Dose-Response Relationship, Drug / Edetic Acid / Free Radical Scavengers / Free Radicals / Hydrogen Peroxide / Hydrogen-Ion Concentration / Ions / Iron / Lysine / Metals / Models, Chemical / Oxidative Stress / Oxygen / Superoxide Dismutase / Time Factors / Vanadates
- (出版サイトへのリンク)
- ● Publication site (DOI): 10.1080/10715760210167
- (文献検索サイトへのリンク)
- ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 11999699
- ● Search Scopus @ Elsevier (PMID): 11999699
- ● Search Scopus @ Elsevier (DOI): 10.1080/10715760210167
(DOI: 10.1080/10715760210167, PubMed: 11999699) Mitsugu Akagawa and K Suyama :
Amine oxidase-like activity of polyphenols. Mechanism and properties.,
European Journal of Biochemistry, Vol.268, No.7, 1953-1963, 2001.- (要約)
- Polyphenols in several oxidation systems gained amine oxidase-like activity, probably due to the formation of the corresponding quinones. In the presence of Cu(II), o- and p-phenolic compounds exhibited amine oxidase-like activity, whereas only the o-phenolic compounds showed the activity in the presence of 1,1-diphenyl-2-picrylhydrazyl radical. The activity was determined by measuring the conversion of benzylamine to benzaldehyde by HPLC. Moreover, gallic acid, chlorogenic acid, and caffeic acid, which are plant polyphenols, converted the lysine residue of bovine serum albumin to alpha-amino-adipic semialdehyde residue, indicating lysyl oxidase-like activity. We also characterized the activity of pyrocatechol, hydroquinone, and pyrogallol in the presence of Cu(II). The oxidative deamination was accelerated at a higher pH, and required O2 and transition metal ions. Furthermore, EDTA markedly inhibited the reaction but not beta-aminopropionitrile, which is a specific inhibitor of lysyl oxidase. Catalase significantly inhibited the oxidation, implying the participation of hydroxyl radical in the reaction, but superoxide dismutase stimulated the oxidation, probably due to its radical formation activity. We discussed the mechanism of the oxidative deamination by polyphenols and the possible significance of the activity for biological systems.
- (キーワード)
- Amine Oxidase (Copper-Containing) / Aminopropionitrile / Benzylamines / Caffeic Acids / Catalase / Catechols / Chelating Agents / Chlorogenic Acid / Chromatography, High Pressure Liquid / Copper / Edetic Acid / Flavonoids / Free Radicals / Gallic Acid / Hydrogen-Ion Concentration / Hydroquinones / Lysine / Models, Chemical / Phenols / Polymers / Protein-Lysine 6-Oxidase / Pyrogallol / Serum Albumin, Bovine / Structure-Activity Relationship / Superoxide Dismutase
- (出版サイトへのリンク)
- ● Publication site (DOI): 10.1046/j.1432-1327.2001.02068.x
- (文献検索サイトへのリンク)
- ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 11277917
- ● Search Scopus @ Elsevier (PMID): 11277917
- ● Search Scopus @ Elsevier (DOI): 10.1046/j.1432-1327.2001.02068.x
(DOI: 10.1046/j.1432-1327.2001.02068.x, PubMed: 11277917) Mitsugu Akagawa and K Suyama :
Characterization of a model compound for the lysine tyrosylquinone cofactor of lysyl oxidase.,
Biochemical and Biophysical Research Communications, Vol.281, No.1, 193-199, 2001.- (要約)
- We characterized a model compound for the lysine tyrosylquinone (LTQ) cofactor of lysyl oxidase which is one of the mammalian copper-dependent amine oxidases. The model compound, 4-butylamino-5-methyl-o-quinone, was prepared from n-butylamine and 4-methylcatechol by the oxidation with sodium iodate and characterized by spectroscopic analyses. The absorption maximum at 494 nm is consistent with that of lysyl oxidase. The model compound was capable of deaminating benzylamine to benzaldehyde at 37 degrees C in buffered aqueous acetonitrile. The aldehyde production was markedly elevated in the presence of the Cu(II)-EDTA complex but inhibited by free Cu(II). The catalytic cycle was observed at pH 10 in the presence of Cu(II), and the pH activity profile showed a broad optimum at about pH 9.0. In the presence of beta-aminopropionitrile and upon deoxygenation with N2 aldelyde, production was decreased. The important features of the reaction were consistent with the enzymatic reaction.
- (キーワード)
- Acetonitriles / Aminopropionitrile / Antioxidants / Benzaldehydes / Benzoquinones / Benzylamines / Butylamines / Catechols / Copper / Edetic Acid / Hydrogen-Ion Concentration / Iodates / Lysine / Magnetic Resonance Spectroscopy / Models, Chemical / Oxygen / Protein-Lysine 6-Oxidase / Quinones / Spectrophotometry / Time Factors / Ultraviolet Rays
- (出版サイトへのリンク)
- ● Publication site (DOI): 10.1006/bbrc.2001.4315
- (文献検索サイトへのリンク)
- ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 11178979
- ● Search Scopus @ Elsevier (PMID): 11178979
- ● Search Scopus @ Elsevier (DOI): 10.1006/bbrc.2001.4315
(DOI: 10.1006/bbrc.2001.4315, PubMed: 11178979) Mitsugu Akagawa and K Suyama :
Mechanism of formation of elastin crosslinks.,
Connective Tissue Research, Vol.41, No.2, 131-141, 2000.- (要約)
- We examined the formation of quaternary pyridinium crosslinks of elastin formed by condensation of lysine and allysine residues using the model compounds propanal (allysine) and n-butylamine (lysine) under quasi-physiological conditions. The resulting pyridinium compounds were characterized and the structure compared with the known pyridinium crosslinks. Three pyridinium compounds were identified and the structures were identical with the skeleton of the crosslinking amino acids, desmosine (DES), isodesmosine (IDE), and pentasine. We concluded that a non-enzymatic pathway is available for the spontaneous generation of pyridinium crosslinks. To elucidate the intermediates and the mechanism of the formation of DES and IDE, we synthesized model intermediates from propanal and n-butylamine, and they were allowed to react in three kinds of solvents. Then, the products were analyzed by an ion-pair reverse-phase HPLC. The results of this model system indicated that DES and IDE can be formed by condensation of dehydromerodesmosine with dehydrolysinonorleucine and by condensation of allysine with dehydrolysinonorleucine, respectively. We also describe the mechanism of DES and IDE crosslinking.
- (キーワード)
- 2-Aminoadipic Acid / Aldehydes / Amino Acids / Butylamines / Chromatography, High Pressure Liquid / Chromatography, Thin Layer / Cross-Linking Reagents / Desmosine / Elastin / Hydrogen-Ion Concentration / Isodesmosine / Lysine / Pyridinium Compounds
- (出版サイトへのリンク)
- ● Publication site (DOI): 10.3109/03008200009067665
- (文献検索サイトへのリンク)
- ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 10992159
- ● Search Scopus @ Elsevier (PMID): 10992159
- ● Search Scopus @ Elsevier (DOI): 10.3109/03008200009067665
(DOI: 10.3109/03008200009067665, PubMed: 10992159) Mitsugu Akagawa, K Yamazaki and K Suyama :
Cyclopentenosine, major trifunctional crosslinking amino acid isolated from acid hydrolysate of elastin.,
Archives of Biochemistry and Biophysics, Vol.372, No.1, 112-120, 1999.- (要約)
- A trifunctional crosslinking amino acid named cyclopentenosine (CP) was isolated from the hydrolysate of bovine nuchal ligament elastin. CP and its derivatives were identified by spectroscopic methods. CP was found to consist of a 2-cyclopenten-1-one structure and its imine-enamine tautomers with enantiomers in H(2)O. A model reaction for the formation of the CP crosslink using model compounds for allysine (propanal) and lysine (n-butylamine) demonstrated that CP is composed of 2-cyclopenten-1-one and alpha, beta, gamma, delta-unsaturated aldehyde derived from three allysine residues. An ion-paired high-performance liquid chromatographic method for the determination of CP was developed. Among various bovine tissues the nuchal ligament had the highest concentration of CP. The age-related changes in the concentration of CP were examined in the aorta from rat (short-lived species) and bovine (long-lived species). The CP content was very low in the newborn rat but increased markedly with growth. After maturity, the CP content remained nearly the same or slightly decreased. In bovine aorta, the CP content scarcely changed from 7 months to 16 years.
- (キーワード)
- Aging / Amino Acids / Animals / Animals, Newborn / Cattle / Chromatography, High Pressure Liquid / Cross-Linking Reagents / Elastin / Hydrolysis / Ligaments / Male / Models, Chemical / Oxidation-Reduction / Pipecolic Acids / Rats / Rats, Sprague-Dawley / Ultraviolet Rays
- (出版サイトへのリンク)
- ● Publication site (DOI): 10.1006/abbi.1999.1462
- (文献検索サイトへのリンク)
- ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 10562423
- ● Search Scopus @ Elsevier (PMID): 10562423
- ● Search Scopus @ Elsevier (DOI): 10.1006/abbi.1999.1462
(DOI: 10.1006/abbi.1999.1462, PubMed: 10562423) Mitsugu Akagawa, Y Wako and K Suyama :
Lysyl oxidase coupled with catalase in egg shell membrane.,
Biochimica et Biophysica Acta, Vol.1434, No.1, 151-160, 1999.- (要約)
- The activity of lysyl oxidase was found in egg shell membrane (ESM) of hens. The activity was determined by measuring the enzymatic conversion of n-butylamine and Nalpha-acetyl-L-lysine to n-butyraldehyde and Nalpha-acetyl-L-allysine, respectively. ESM lysyl oxidase was significantly inhibited by beta-aminopropionitrile, chelating agents, and deoxygenation, consistent with the known properties of lysyl oxidase. Nevertheless, ESM lysyl oxidase was insoluble in urea solution, suggesting that it complexes with ESM. These findings support previous reports indicating the presence of lysine-derived cross-links in ESM and the necessity of lysyl oxidase located in the isthmus of the hen oviduct for the biosynthesis of ESM. Lysyl oxidase secreted around the egg white from the isthmus may initiate the cross-linking reaction of ESM protein, and remain as the constituent of ESM. Moreover, the H(2)O(2) released by lysyl oxidase in ESM was completely decomposed by coexisting catalase activity. ESM lysyl oxidase activity was greatly elevated in the presence of H(2)O(2), probably due to the O(2) produced by catalase. These findings indicate that lysyl oxidase is coupled with catalase in ESM. This coupling enzyme system was considered to be involved in the biosynthesis of ESM and to protect the embryo against H(2)O(2).
- (キーワード)
- Animals / Binding Sites / Butylamines / Catalase / Chickens / Egg Shell / Enzyme Activation / Hydrogen-Ion Concentration / Membrane Proteins / Oxidation-Reduction / Protein-Lysine 6-Oxidase / Temperature / Vitelline Membrane
- (出版サイトへのリンク)
- ● Publication site (DOI): 10.1016/s0167-4838(99)00169-7
- (文献検索サイトへのリンク)
- ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 10556569
- ● Search Scopus @ Elsevier (PMID): 10556569
- ● Search Scopus @ Elsevier (DOI): 10.1016/s0167-4838(99)00169-7
(DOI: 10.1016/s0167-4838(99)00169-7, PubMed: 10556569) - MISC
- 辻 シャフィカ, 池本 一人, 赤川 貢 :
PQQ の体脂肪減少機能 -肥満マウス,ミジンコおよび脂肪細胞からのエビデンス-,
New Food Industry, Vol.65, No.1, 11-17, 2023年.- (キーワード)
- 肥満 / 体脂肪 / PQQ / ミトコンドリア / 脂肪減少 / ダイエット / BioPQQ / obesity / body fat / mitochondria / fat reduction / diet
- (文献検索サイトへのリンク)
- ● CiNii @ 国立情報学研究所 (CRID): 1520576435525090560
(CiNii: 1520576435525090560)
- 総説・解説
- 研究者総覧に該当データはありませんでした。
- 講演・発表
- Nur Mohamad Syafiqah Ishak, Kazuhito Ikemoto, Midori Kikuchi, Mariko Ogawa and Mitsugu Akagawa :
Pyrroloquinoline quinone attenuates fat accumulation in obese mice fed with a high-fat diet, Daphnia magna supplied with a high amount of food, and 3T3-L1 adipocytes,
22nd IUNS-International Congress of Nutrition, Dec. 2022. 鈴木 咲子, 赤川 貢, 西川 美宇, 生城 真一, 金子 一郎, 加藤 陽二 :
細胞内における新型コロナウイルス酵素Main proteaseへの茶成分の結合,
日本農芸化学会2024年度大会, 2024年3月. 井関 菜月, 古居 優季, 浅田 智恵, 藤田 綾香, 坂本 裕香, 赤川 貢, 石井 剛志 :
珈琲による脂っこさのリセット作用の科学的検証,
日本農芸化学会2024年度大会, 2024年3月. 井関 菜月, 古居 優季, 赤川 貢, 柏 計雄, 石井 剛志 :
茶ポリフェノールによる脂っこさのリセット作用の科学的検証(2),
第19回日本カテキン学会年次学術大会, 2023年12月. 亀井 優輝, 赤川 貢 :
物理化学的に血管石灰化を抑制する食品因子の探索,
第28回日本フードファクター学会学術集会, 2023年11月. 永良 祐樹, 亀井 優輝, 内藤 健太郎, 赤川 貢 :
アカメガシワ由来ポリフェノール,ベルゲニンによるミトコンドリア新生促進作用の解明,
第56回日本栄養・食糧学会 中国・四国支部大会, 2023年10月. 永良 祐樹, 亀井 優輝, 内藤 健太郎, 赤川 貢 :
アカメガシワ由来ポリフェノール,ベルゲニンのPGC1α/SIRT1経路を介したミトコンドリア新生促進作用の解明,
第77回日本栄養・食糧学会大会, 2023年5月. 赤川 貢 :
生活習慣病を予防・改善する機能性食品因子の探索と作用機構の解析,
日本農芸化学会中四国支部 第37回若手シンポジウム (第13 回農芸化学の未来開拓セミナー), 2023年5月. 浅田 智恵, 古居 優季, 道行 汐奈, 泉 英里, 坂本 裕香, 赤川 貢, 石井 剛志 :
珈琲による口腔内リセット作用の科学的検証:水溶性焙煎成分の強力な乳化作用,
第18回日本カテキン学会年次学術大会, 2022年12月. 西川 綾花, 飯泉 陽介, 阪本 龍司, 赤川 貢 :
ジカルボニルストレスに対するスペルミンの細胞保護効果の解明,
第27回日本フードファクター学会, 2022年10月.
- 研究会・報告書
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- 特許
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- 作品
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- 補助金・競争的資金
- 加齢性網膜疾患を予防する食品因子の探索 (研究課題/領域番号: 23K10871 )
ピロロキノリンキノン受容体の同定と機能解析:ビタミン様物質の新規生理作用の解明 (研究課題/領域番号: 21K19073 )
渋味飲料と料理の食事相性の分子科学的検証 (研究課題/領域番号: 23K20669 )
食品因子の胃粘膜細胞に対するレプチン分泌刺激作用の解明と抗肥満効果の検証 (研究課題/領域番号: 19K11720 )
ポリフェノール・パラドックスの解明 (研究課題/領域番号: 17H00818 )
レプチン抵抗性を改善する食品因子の探索とその抗肥満効果の検証 (研究課題/領域番号: 16K00859 )
渋味の生理的意義の究明 (研究課題/領域番号: 16H03032 )
インスリンシグナル活性化作用を持つ香辛料成分の探索とその抗糖尿病効果の検証 (研究課題/領域番号: 25350131 )
ビタミン候補物質ピロロキノリンキノン(PQQ)と結合する蛋白質の同定と機能解析 (研究課題/領域番号: 22780124 )
食品ポリフェノールの酸化付加反応による蛋白質の修飾と生理作用発現機構の解明 (研究課題/領域番号: 20780101 )
緑茶カテキンのシステイン残基への付加によるタンパク質の機能制御機構の解明 (研究課題/領域番号: 18780104 )
研究者番号(70405356)による検索
- その他
- 研究者総覧に該当データはありませんでした。
2024年10月10日更新
- 専門分野・研究分野
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- 所属学会・所属協会
- 日本フードファクター学会
次世代吸収研究会 - 委員歴・役員歴
- 日本フードファクター学会 (理事 [2021年10月])
次世代吸収研究会 (理事 [2023年4月]) - 受賞
- 研究者総覧に該当データはありませんでした。
- 活動
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更新
2024年10月5日更新
Jグローバル
- Jグローバル最終確認日
- 2024/10/5 01:07
- 氏名(漢字)
- 赤川 貢
- 氏名(フリガナ)
- アカガワ ミツグ
- 氏名(英字)
- Akagawa Mitsugu
- 所属機関
- 徳島大学大学院 教授
リサーチマップ
- researchmap最終確認日
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2024年10月5日更新
- 研究者番号
- 70405356
- 所属(現在)
- 2024/4/1 : 徳島大学, 大学院医歯薬学研究部(医学域), 教授
- 所属(過去の研究課題
情報に基づく)*注記 - 2022/4/1 – 2024/4/1 : 徳島大学, 大学院医歯薬学研究部(医学域), 教授
2017/4/1 – 2021/4/1 : 大阪府立大学, 生命環境科学研究科, 准教授
2016/4/1 : 大阪府立大学, 生命環境科学研究科, 講師
2013/4/1 – 2015/4/1 : 大阪府立大学, 生命環境科学研究科(系), 講師
2011/4/1 : 大阪府立大学, 生命環境科学研究科(系), 助教
2011/4/1 : 大阪府立大学, 生命環境科学研究科, 講師
2007/4/1 – 2010/4/1 : 大阪府立大学, 生命環境科学研究科, 助教
2006/4/1 : 大阪府立大学, 生命環境科学研究科, 助手
- 審査区分/研究分野
-
研究代表者
生物系 / 農学 / 農芸化学 / 食品科学
総合系 / 複合領域 / 生活科学 / 食生活学
小区分59040:栄養学および健康科学関連研究代表者以外
総合系 / 複合領域 / 生活科学 / 食生活学
中区分38:農芸化学およびその関連分野
小区分08030:家政学および生活科学関連
- キーワード
-
研究代表者
カテキン / ポリフェノール / 緑茶 / 癌 / エピガロカテキンガレート / ガン / 蛋白質 / p68 / エピガロカテキンがレート / ミリセチン / ピロロキノリンキノン / ビタミン / 酸化還元補酵素 / キノン / 機能性食品因子 / 香辛料 / 機能性食品 / 2型糖尿病 / インスリン抵抗性 / プロテインチロシンホスファターゼ1B / 2型糖尿病 / 機能性食品成分 / レプチン / 肥満 / イソチオシアネート / レプチンシグナル / 抗肥満 / 食品因子 / レプチン抵抗性 / leptin / obesity / catechin / polyphenol / green tea / 緑茶カテキン / 食品機能 / 胃粘膜細胞 / 加齢性網膜疾患 / 加齢黄斑変性 / リポフスチン / アミノーカルボニル反応
研究代表者以外
渋味 / 難吸収性ポリフェノール / 分子挙動 / 細胞膜非透過性 / タンパク質凝集能 / カテキン類 / テアフラビン類 / ウーロンホモビスフラバン類 / ポリフェノール / 渋味刺激 / 標的タンパク質 / 会合性 / えぐ味 / 嗜好機能(食べ合わせ) / 生理的意義 / 生理機能発現機構 / 標的探索技術 / カテキン / テアフラビン / ウーロンホモビスフラバン / ロスマリン酸 / 脂質吸収阻害 / 抗肥満 / 味覚評価 / 生理機能 / 分子メカニズム / プロシアニジン / 分子会合性 / 細胞膜蓄積性 / 味覚受容 / 生体調節機能 / 標的分子 / 生体リズム / 体内動態 / 生態調節機能 / ピロロキノリンキノン / GPCR / 受容体 / Gタンパク質共役型受容体 / 代謝物感受性受容体 / 食事相性 / 渋味飲料 / 油脂 / 界面活性作用 / 口腔内リセット作用 / エマルション / 乳化作用 / 茶ポリフェノール / 渋味ポリフェノール / ガレート型カテキン類 / バリア機能 / レプチン分泌