酸素受容・活性化に伴うリガンドシグナルの生成と制御

• Project Area: Oxygen biology: a new criterion for integrated understanding of life
• Project/Area Number: 26111011
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: The University of Tokyo (2015-2018); Nagoya University (2014)
• Principal Investigator: 内田 浩二 東京大学, 大学院農学生命科学研究科(農学部), 教授 (40203533)
• Co-Investigator(Kenkyū-buntansha): 西田 基宏 大学共同利用機関法人自然科学研究機構(新分野創成センター、アストロバイオロジーセンター、生命創成探究, 生命創成探究センター, 教授 (90342641) ; 居原 秀 大阪府立大学, 理学(系)研究科(研究院), 准教授 (60254447) ; 柴田 貴広 名古屋大学, 生命農学研究科, 准教授 (80447838)
• Project Period (FY): 2014-07-10 – 2019-03-31
• Project Status: Granted (Fiscal Year 2018)
• Budget Amount: ¥113,750,000 (Direct Cost: ¥87,500,000、Indirect Cost: ¥26,250,000); Fiscal Year 2018: ¥22,230,000 (Direct Cost: ¥17,100,000、Indirect Cost: ¥5,130,000); Fiscal Year 2017: ¥22,230,000 (Direct Cost: ¥17,100,000、Indirect Cost: ¥5,130,000); Fiscal Year 2016: ¥22,490,000 (Direct Cost: ¥17,300,000、Indirect Cost: ¥5,190,000); Fiscal Year 2015: ¥22,360,000 (Direct Cost: ¥17,200,000、Indirect Cost: ¥5,160,000); Fiscal Year 2014: ¥24,440,000 (Direct Cost: ¥18,800,000、Indirect Cost: ¥5,640,000)
• Keywords: 活性酸素種 / ケミカルバイオロジー / タンパク質修飾 / リモデリング / レドックス

Outline of Annual Research Achievements

1.生体内酸化修飾分子の網羅的解析：LC-ESI/MS/MSを用いて、マウス個体、培養細胞における、酸化修飾イミダゾールジペプチドの産生と酸化ストレスとの関連性を明らかにした。また、安定同位体酸素、ラジカル補足剤を用いて酸化修飾の分子機構を明らかにした。
2.酸素活性化を起源とするタンパク質酸化修飾による生体防御応答機構の解析：タンパク質をピロール化する内因性因子の同定を目標に、糖質および脂質などについてスクリーニングを行なった結果、脂質過酸化生成物であり、解糖系分子でもあるグリコールアルデヒドを同定した。一方、植物性小分子酸素センサーであるポリフェノール類に関して、抗酸化剤の作用により生成するタンパク質カルボニルが自然抗体のエピトープとして認識される作用機構について詳細に解析した結果、タンパク質表面の陰性荷電がその認識に関わっていることが推測された。
3.タンパク質酸化修飾を基軸にした修復・再生応答機構の解明：ホモシステイン化アルブミンの研究では、ホモシステイン化が遊離SH基だけでなく、ジスルフィド結合にも生じるという画期的発見に至った。心筋が低酸素環境下で活性酸素を生成する機構の解析の結果、アントラサイクリン系抗がん剤は心筋細胞に多く含まれる酸素貯蔵タンパク質ミオグロビンから鉄を引き抜き、貯蔵酸素を解離させることで低酸素ストレスを誘発することを見出した。また、低酸素誘導性のTRPC3チャネルタンパク質がNADPH酸化酵素（NOX2）を複合体形成依存的に安定化し、増加したNOX2が活性酸素を生成することで、心筋萎縮を誘発することをマウスで明らかにした。

Current Status of Research Progress

1: Research has progressed more than it was originally planned.

Reason

生体内酸化修飾分子の網羅的解析では、イミダゾールジペプチドの2-oxo化の分子機構の解明に到達している。オリジナリティの高いタンパク質のピロール化では、内因性のピロール化因子を同定しており、酸素に起因する修飾タンパク質の生物学的意義の解明につながる可能性を示唆する。また、血清アルブミンのジスルフィド結合に対するホモシステイン化は画期的発見であり、SH化合物のリザーバーとしての血清アルブミンの新たな機能性の解明につながるものと期待される。

Strategy for Future Research Activity

最終年度にあたり、成果発表（論文）を念頭に以下の項目について重点的に進める。
1.酸化修飾イミダゾールジペプチドが、シグナル分子として機能しているかどうかを様々なモデル実験系で検証する。また、酸化修飾に関連するニトロ化、メルカプト化など他の修飾分子の探索、他の化合物（タンパク質など）中での修飾イミダゾール基の探索を行う。
2.グリコールアルデヒドによるピロール化機構について詳細に解析するとともに、脾細胞などを用い、ピロール化タンパク質による自然免疫応答の分子機構を解析する。
3.活性酸素による心筋の可塑性にはミトコンドリア分裂が関与しており、そのメカニズムとしてdynamin-related protein 1 (Drp1)タンパク質C末端にあるシステイン修飾が関与することも見出している。今後は、Drp1のシステイン修飾様式とDrp1活性との関連を明らかにし、そこを特異的に阻害することで心疾患リスクが軽減されることを検証する。

Research Products

• [Journal Article] Identification of Polyphenol-Specific Innate Epitopes That Originated from a Resveratrol Analogue (2018)
  • Author(s): Furuhashi, M., Hatasa, Y., Kawamura, S., Shibata, T., Akagawa, M., Uchida, K.
  • Journal Title: Sci. Rep. Volume: 56 Pages: 470-4712
  • DOI: 10.1021/acs.biochem.7b00409
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] 8-Nitro-cGMP Attenuates the Interaction between SNARE Complex and Complexin through S-Guanylation of SNAP-25 (2018)
  • Author(s): Kishimoto Y, Kunieda K, Kitamura A, Kakihana Y, Akaike T, Ihara H.
  • Journal Title: ACS chemical neuroscience Volume: 9 Pages: 217-223
  • DOI: 10.1021/acschemneuro.7b00363
  • Peer Reviewed / Open Access
• [Journal Article] Involvement of nitric oxide/reactive oxygen species signaling via 8-nitro-cGMP formation in 1-methyl-4-phenylpyridinium ion-induced neurotoxicity in PC12 cells and rat cerebellar granule neurons. (2018)
  • Author(s): Masuda Kumiko、Tsutsuki Hiroyasu、Kasamatsu Shingo、Ida Tomoaki、Takata Tsuyoshi、Sugiura Kikuya、Nishida Motohiro、Watanabe Yasuo、Sawa Tomohiro、Akaike Takaaki、Ihara Hideshi
  • Journal Title: Biochemical and biophysical research communications Volume: 495 Pages: 2165-2170
  • DOI: 10.1016/j.bbrc.2017.12.088
  • Peer Reviewed / Open Access
• [Journal Article] TRPC3 participates in angiotensin II type 1 receptor-dependent stress-induced slow increase in intracellular Ca2+ concentration in mouse cardiomyocytes. (2018)
  • Author(s): Yamaguchi Y, Iribe G, Kaneko T, Takahashi K, Numaga-Tomita T, Nishida M, Birnbaumer L, Naruse K.
  • Journal Title: J Physiol Sci Volume: 印刷中 Pages: 1-12
  • DOI: 10.1007/s12576-016-0519-3
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Adductome-based identification of biomarkers for lipid peroxidation. (2017)
  • Author(s): Shibata T, Shimizu K, Hirano K, Nakashima F, Kikuchi R, Matsushita T, Uchida K.
  • Journal Title: J. Biol. Chem. Volume: 292(20) Pages: 8223-8235
  • DOI: 10.1074/jbc.m116.762609
  • Peer Reviewed / Open Access
• [Journal Article] Roles of 5-lipoxygenase and cyclooxygenase-2 in the biosynthesis of hemiketals E2 and D2 by activated human leukocytes (2017)
  • Author(s): Gimenez-Bastida JA, Shibata T, Uchida K, Schneider C.
  • Journal Title: FASEB J. Volume: 31 Pages: 1867-1878
  • DOI: 10.1096/fj.201601136r
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] TRPC3-Nox2 complex mediates doxorubicin-induced myocardial atrophy. (2017)
  • Author(s): Shimauchi Tsukasa、Numaga-Tomita Takuro、Ito Tomoya、Nishimura Akiyuki、Matsukane Ryosuke、Oda Sayaka、Hoka Sumio、Ide Tomomi、Koitabashi Norimichi、Uchida Koji、Sumimoto Hideki、Mori Yasuo、Nishida Motohiro
  • Journal Title: JCI Insight. Volume: 2 Pages: 1-10
  • DOI: 10.1172/jci.insight.93358
  • Peer Reviewed / Open Access
• [Journal Article] TRPC6 counteracts TRPC3-Nox2 protein complex leading to attenuation of hyperglycemia-induced heart failure in mice. (2017)
  • Author(s): Oda Sayaka、Numaga-Tomita Takuro、Kitajima Naoyuki、Toyama Takashi、Harada Eri、Shimauchi Tsukasa、Nishimura Akiyuki、Ishikawa Tatsuya、Kumagai Yoshito、Birnbaumer Lutz、Nishida Motohiro
  • Journal Title: Sci Rep Volume: 7 Pages: 1-10
  • DOI: 10.1038/s41598-017-07903-4
  • NAID: 120006343876
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Cysteinyl-tRNA synthetase governs cysteine polysulfidation and mitochondrial bioenergetics. (2017)
  • Author(s): Akaike Takaaki、、、Nishida Motohiro（4）、、、、、、Fujii Shigemoto（20）、、、Motohashi Hozumi（26）
  • Journal Title: Nature Commun Volume: 8 Pages: 1-10
  • DOI: 10.1038/s41467-017-01311-y
  • NAID: 120006365562
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Exposure to Electrophiles Impairs Reactive Persulfide-dependent Redox Signaling in Neuronal Cells (2017)
  • Author(s): Ihara Hideshi、Kasamatsu Shingo、Kitamura Atsushi、Nishimura Akira、Tsutsuki Hiroyasu、Ida Tomoaki、Ishizaki Kento、Toyama Takashi、Yoshida Eiko、Abdul Hamid Hisyam、Jung Minkyung、Matsunaga Tetsuro、Fujii Shigemoto、Sawa Tomohiro、Nishida Motohiro、Kumagai Yoshito、Akaike Takaaki
  • Journal Title: Chemical Research Toxicology Volume: 30 Pages: 1673-1684
  • DOI: 10.1021/acs.chemrestox.7b00120
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The purinergic P2Y6 receptor heterodimerizes with the angiotensin AT1 receptor to promote angiotensin II-induced hypertension. (2017)
  • Author(s): A. Nishimura, C. Sunggip, H. Tozaki-Saitoh, T. Shimauchi, T. Numaga-Tomita, K. Hirano, T. Ide, J-M. Boeynaems, H. Kurose, M. Tsuda, B. Robaye, K. Inoue and M. Nishida
  • Journal Title: Sci Signal. Volume: Jan 19;9(411)
  • DOI: 10.1126/scisignal.aac9187
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] MiR30‐GALNT1/2 Axis‐Mediated Glycosylation Contributes to the Increased Secretion of Inactive Human Prohormone for Brain Natriuretic Peptide (proBNP) From Failing Hearts (2017)
  • Author(s): Nakagawa Y, Nishikimi T, Kuwahara K, Fujishima A, Oka S, Tsutamoto T, Kinoshita H, Nakao K, Cho K, Inazumi H, Okamoto H, Nishida M, Kato T, Fukushima H, Yamashita JK, Wijnen WJ, Creemers EE, Kangawa K, Minamino N, Nakao K, Kimura T.
  • Journal Title: J. Am. Heart Assoc. Volume: 6
  • DOI: 10.1161/jaha.116.003601
  • NAID: 120006360780
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Redox regulation of electrophilic signaling by reactive persulfides in cardiac cells. (2017)
  • Author(s): Nishida M, Nishimura A, Matsunaga T, Motohashi H, Kasamatsu S, Akaike T.
  • Journal Title: Free radical biology & medicine Volume: 印刷中 Pages: 132-140
  • DOI: 10.1016/j.freeradbiomed.2017.01.024
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] プリン作動性シグナルの心血管系における役割 (2017)
  • Author(s): 西村明幸、西田基宏
  • Journal Title: 日本薬理学雑誌 Volume: 149 Pages: 84-90
  • NAID: 130005306336
• [Journal Article] Identification of C1q as a binding protein for advanced glycation end products (2016)
  • Author(s): Chikazawa, M., Shibata, T., Hatasa, Y., Hirose, S., Otaki, N., Nakashima, F., Ito, M., Machida, S., Maruyama, S., Uchida, K.
  • Journal Title: Biochemistry Volume: 55 Pages: 435-446
  • DOI: 10.1021/acs.biochem.5b00777
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Oxidative deamination of serum albumins by (-)-epigallocatechin-3-O-gallate: A potential mechanism for the formation of innate antigens by antioxidants. (2016)
  • Author(s): Hatasa, Y., Chikazawa, M., Furuhashi, M., Nakashima, F., Shibata, T., Kondo, T., Akagawa, M., Hamagami, H., Tanaka, H., Tachibana, H., Uchida, K.
  • Journal Title: PLoS ONE Volume: 11
  • DOI: 10.1371/journal.pone.0153002
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Identification of lactate dehydrogenase as a mammalian pyrroloquinoline quinone (PQQ)-binding protein. (2016)
  • Author(s): Akagawa, M., Minematsu, K., Shibata, T., Kondo, T., Ishii, T., and Uchida, K.
  • Journal Title: Sci. Rep. Volume: 6 Pages: 26723-26723
  • DOI: 10.1038/srep26723
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Membrane lipid peroxidation in neurodegeneration: Role of thrombin and proteinase-activated receptor-1 (2016)
  • Author(s): Citron, B. A., Ameenuddin, S., Uchida, K., Suo, W. Z., SantaCruz, K., and Festoff, B. W.
  • Journal Title: Brain Res. Volume: 1643 Pages: 10-17
  • DOI: 10.1016/j.brainres.2016.04.071
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Methylglyoxal, a glycolysis side-product, induces Hsp90 glycation and YAP-mediated tumor growth and metastasis (2016)
  • Author(s): Nokin, M. J., Durieux, F., Peixoto, P., Chiavarina, B., Peulen, O., Blomme, A., Turtoi, A., Costanza, B., Smargiasso, N., Baiwir, D., De Tullio, P., Bianchi, E., Thiry, M., Uchida, K., Spiegel, D. A., Hutton, C. A., De Pauw, E., Delvenne, P., Belpomme, D., Castronovo, D., and Bellahcène, A.
  • Journal Title: eLife Volume: 5
  • DOI: 10.7554/elife.19375
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Screening of Transient Receptor Potential Canonical Channel Activators Identifies Novel Neurotrophic Piperazine Compounds. (2016)
  • Author(s): S. Sawamura, M. Hatano, Y. Takada, K. Hino, T. Kawamura, J. Tanikawa, H. Nakagawa, H. Hase, A. Nakao, M. Hirano, R. Rotrattanadumrong, S. Kiyonaka, M.X. Mori, M. Nishida, Y. Hu, R. Inoue, R. Nagata and Y. Mori
  • Journal Title: Mol Pharmacol. Volume: 89(3) Pages: 348-363
  • DOI: 10.1124/mol.115.102863
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Sustained bAR stimulation mediates cardiac insulin resistance in a PKA-dependent manner (2016)
  • Author(s): S. Mangmool, T. Denkaew, S. Phosri, D. Pinthong, W. Parichatikanond, T. Shimauchi and M. Nishida
  • Journal Title: Molecular Endocrinology Volume: 30(1) Pages: 118-132
  • DOI: 10.1210/me.2015-1201
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Recent progress in studies on the health benefits of pyrroloquinoline quinone (2016)
  • Author(s): Akagawa, M., Nakano, M., Ikemoto, K.
  • Journal Title: Biosci. Biotechnol. Biochem. Volume: 80 Pages: 13-22
  • DOI: 10.1080/09168451.2015.1062715
  • Peer Reviewed
• [Journal Article] Synthesis of radioiodinated probes to evaluate the biodistribution of a potent TRPC3 inhibitor. (2016)
  • Author(s): M. Hagimori, T. Murakami, K. Shimizu, M. Nishida, T. Ohshima, T. Mukai
  • Journal Title: Medicinal Chemical Communications Volume: 7 Pages: 1003-1006
  • DOI: 10.1039/c6md00023a
  • Peer Reviewed / Open Access
• [Journal Article] Methylmercury, an environmental electrophile capable of activation and disruption of the Akt/CREB/Bcl-2 signal transduction pathway in SH-SY5Y cells. (2016)
  • Author(s): Unoki T, Abiko Y, Toyama T, Uehara T, Tsuboi K, Nishida M, Kaji T, Kumagai Y.
  • Journal Title: Scientific Reports Volume: 6 Pages: 1-10
  • DOI: 10.1038/srep28944
  • NAID: 120005822867
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] TRPC3 positively regulates reactive oxygen species driving maladaptive cardiac remodeling (2016)
  • Author(s): Kitajima N., Numaga-Tomita T., Watanabe M., Kuroda T., Nishimura A., Miyano K., Yasuda S., Kuwahara K., Sato Y., Ide T., Birnbaumer L., Sumimoto H., Mori Y. and Nishida M
  • Journal Title: Sci Rep Volume: 6 Pages: 37001-37001
  • DOI: 10.1038/srep37001
  • NAID: 120006323744
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] TRPC3-GEF-H1 axis mediates pressure overload-induced cardiac fibrosis (2016)
  • Author(s): Numaga-Tomita T., Kitajima N., Kuroda T., Nishimura A., Miyano K., Yasuda S., Kuwahara K., Sato Y., Ide T., Birnbaumer L., Sumimoto H., Mori Y. and Nishida M.
  • Journal Title: Sci Rep Volume: 6 Pages: 39383-39383
  • DOI: 10.1038/srep39383
  • NAID: 120005997825
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Redox signaling regulated by electrophiles and reactive sulfur species (2016)
  • Author(s): Nishida M, Kumagai Y, Ihara H, Fujii S, Motohashi H, Akaike T.
  • Journal Title: J. Clin. Biochem. Nutr. Volume: 58 Issue: 2 Pages: 1-8
  • DOI: 10.3164/jcbn.15-111
  • NAID: 130005132519
  • ISSN: 0912-0009, 1880-5086
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] アダクトーム解析法を用いた疾患バイオマーカーの探索 (2016)
  • Author(s): 柴田貴広、内田浩二
  • Journal Title: バイオサイエンスとインダストリー Volume: 74 Pages: 26-29
  • NAID: 40020705853
• [Journal Article] Redox signaling regulated by an electrophilic cyclic nucleotide and reactive cysteine persulfides. (2016)
  • Author(s): Fujii S, Sawa T, Nishida M, Ihara H, Ida T, Motohashi H, Akaike T.
  • Journal Title: Arch Biochem Biophys Volume: 595 Pages: 140-146
  • DOI: 10.1016/j.abb.2015.11.008
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] TRPC3 amplifies B-cell receptor-induced ERK signalling via protein kinase D-dependent Rap1 activation. (2016)
  • Author(s): T. Numaga-Tomita, M. Nishida, J.W. Jr. Putney and Y. Mori
  • Journal Title: Biochem J. Volume: 473(2) Pages: 201-210
  • DOI: 10.1042/bj20150596
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Elastin modification by 4-hydroxynonenal in hairless mice exposed to UV-A. Role in photoaging and actinic elastosis (2015)
  • Author(s): Larroque-Cardoso, P., Camaré, C., Nadal-WollboldF., Grazide, M. H., Pucelle, M., Garoby-Salom, S., Bogdanowicz, P., Josse, G., Schmitt, A. M., Uchida, K., Zarkovic, K., Salvayre, R., and Nègre-Salvayre, A.
  • Journal Title: J. Invest. Dermatol. Volume: 135 Pages: 1873-1881
  • DOI: 10.1038/jid.2015.84
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Abnormal myofiber morphology and limb dysfunction in claudication (2015)
  • Author(s): Koutakis, P., Myers, S. A., Cluff, K., Ha, D. M., Haynatzki, G., McComb, R. D., Uchida, K., Miserlis, D., Papoutsi, E., Johanning, J. M., Casale, G. P., and Pipinos, I. I.
  • Journal Title: J. Surg. Res. Volume: J. Surg. Res. Pages: 172-179
  • DOI: 10.1016/j.jss.2015.02.011
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Generation of adducts of 4-hydroxy-2-nonenal with heat shock 60kDa protein 1 in human promyelocytic HL-60 and monocytic THP-1 cell lines (2015)
  • Author(s): Arcaro, A., Daga, M., Paolo Cetrangolo, G., Ciamporcero, E., Lepore, A., Pizzimenti, A., Petrella, C., Graf, M., Uchida, U., Mamone, G., Ferranti, P., Julian Ames, R., Palumbo, G., BarreraG., and Gentile, F.
  • Journal Title: Oxid Med. Cell. Longev. Volume: 2015 Pages: 296146-296146
  • DOI: 10.1155/2015/296146
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Divergent Roles of CAAX Motif-signaled Posttranslational Modifications in the Regulation and Subcellular Localization of Ral GTPases. (2015)
  • Author(s): LR Gentry, A. Nishimura, A.D. Cox, T.D. Martin, D. Tsygankov, M. Nishida, T.C. Elston and C.J. Der
  • Journal Title: The Journal of Biological Chemistry Volume: 290(37) Pages: 22851-22861
  • DOI: 10.1074/jbc.m115.656710
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Reactive Sulfur Species-Mediated Activation of the Keap1-Nrf2 Pathway by 1,2-Naphthoquinone through Sulfenic Acids Formation under Oxidative Stress. (2015)
  • Author(s): Shinkai Y, Abiko Y, Ida T, Miura T, Kakehashi H, Ishii I, Nishida M, Sawa T, Akaike T, Kumagai Y.
  • Journal Title: Chemical Research in Toxicology Volume: 印刷中 Pages: 838-847
  • DOI: 10.1021/tx500416y
  • NAID: 130005483607
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Measurement of glucose uptake in cultured cells (2015)
  • Author(s): Yamamoto, N., Ueda-Wakagi, M., Sato, T., Kawasaki, K., Sawada, K., Kawabata, K., Akagawa, M., Ashida, H.
  • Journal Title: Curr. Protoc. Pharmacol. Volume: 71 Pages: 1-12
  • DOI: 10.1002/0471141755
  • Peer Reviewed
• [Journal Article] Production of hypoallergenic cocoa beans by a pregermination treatment method (2015)
  • Author(s): Handoyo, T., Akagawa, M., Kim, K.
  • Journal Title: J. Plant Biotechnol. Volume: 42 Pages: 123-128
  • DOI: 10.5010/jpb.2015.42.2.123
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Aldehyde adducts generated during lipid peroxidation modification of proteins (2015)
  • Author(s): Uchida K
  • Journal Title: Free Radic Res. Volume: 49 Pages: 896-904
  • DOI: 10.3109/10715762.2015.1036052
  • Peer Reviewed
• [Journal Article] Special issue on "Recent progress in lipid peroxidation based on novel approaches" (2015)
  • Author(s): Yin H, Niki E, Uchida K.
  • Journal Title: Free Radic. Res. Volume: 49 Pages: 813-815
  • DOI: 10.3109/10715762.2015.1021697
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] 15-Deoxy-Δ12, 14-prostaglandin J2 as an electrophilic mediator (2015)
  • Author(s): Shibata T.
  • Journal Title: Biosci. Biotechnol. Biochem. Volume: 79 Pages: 1044-1049
  • DOI: 10.1080/09168451.2015.1012149
  • Open Access
• [Journal Article] 内因性抗原としての陰性荷電分子の生成と制御 (2015)
  • Author(s): 近澤未歩、内田浩二
  • Journal Title: 生化学 Volume: 87 Pages: 776-780
  • NAID: 40020687514
• [Journal Article] Palmitate induces insulin resistance in human HepG2 hepatocytes by enhancing ubiquitination and proteasomal degradation of key insulin signaling molecules (2015)
  • Author(s): Ishii M, Maeda A, Tani S, Akagawa M.
  • Journal Title: Arch. Biochem. Biophys. Volume: 566 Pages: 26-35
  • DOI: 10.1016/j.abb.2014.12.009
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Toll-like receptors as a target of food-derived anti-Inflammatory compounds. (2014)
  • Author(s): Shibata, T., Nakashima, F., Honda, K., Lu, Y. J., Kondo, T., Ushida, Y., Aizawa, K., Suganuma, H., Oe, S., Tanaka, H., Takahashi, T. and Uchida, K.
  • Journal Title: J. Biol. Chem. Volume: 289 Pages: 32757-32772
  • DOI: 10.1074/jbc.m114.585901
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Functional interaction between cyclooxygenase-2 and p53 in response to an endogenous electrophile (2014)
  • Author(s): Kumagai, T., Usami, H., Matsukawa, N., Nakashima, F., Chikazawa, M., Shibata, T., Noguchi, N., and Uchida, K.
  • Journal Title: Redox Biol. Volume: 4 Pages: 74-86
  • DOI: 10.1016/j.redox.2014.11.011
  • Peer Reviewed / Open Access
• [Journal Article] Inhibition of N-type Ca2+ channels ameliorates an imbalance in cardiac autonomic nerve activity and prevents lethal arrhythmias in mice with heart failure (2014)
  • Author(s): Yamada Y, Kinoshita H, Kuwahara K, Nakagawa Y, Kuwabara Y, Minami T, Yamada C, Shibata J, Nakao K, Cho K, Arai Y, Yasuno S, Nishikimi T, Ueshima K, Kamakura S, Nishida M, Kiyonaka S, Mori Y, Kimura T, Kangawa K, Nakao K.
  • Journal Title: Cardiovascular Research Volume: 104 Pages: 183-193
  • DOI: 10.1093/cvr/cvu185
  • NAID: 120005619790
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Cardiovascular Aging Regulated by Heterodimerization of Angiotensin AT1 Receptor with Purinergic P2Y6 Receptor (2018)
  • Author(s): Nishida M.
  • Organizer: Angiotensin Gordon Research Conference 2018
  • Int'l Joint Research / Invited
• [Presentation] S-チオール化血清アルブミンによる炎症誘導機構の解明 (2018)
  • Author(s): 中島史恵、柴田貴広、菊地良介、松下正、内田浩二
  • Organizer: 日本農芸化学会2018年度大会
• [Presentation] 自然抗体エピトープを有する食品成分の探索 (2018)
  • Author(s): 三輪恭行、今堀夏奈美、古橋麻衣、柴田貴広、内田浩二
  • Organizer: 日本農芸化学会2018年度大会
• [Presentation] ポリフェノールオキシダーゼによる茶カテキンの自然抗体リガンド生成能の増強 (2018)
  • Author(s): 今堀夏奈美、三輪恭行、李相美、柴田貴広、内田浩二
  • Organizer: 日本農芸化学会2018年度大会
• [Presentation] 酸化ストレスに対する細胞内カルノシンの神経保護効果 (2017)
  • Author(s): 山陰茜、垣花優希、柴田貴広、内田浩二、居原秀
  • Organizer: 第17回日本NO学会学術集会
• [Presentation] 酸化ストレスに依存した酸化イミダゾールジペプチドの産生 (2017)
  • Author(s): 垣花優希、柴田貴広、内田浩二、居原秀
  • Organizer: 第70回日本酸化ストレス学会学術集会
• [Presentation] Detection and quantification of 2-oxo-histidine-containing dipeptides (2017)
  • Author(s): Ihara H, Kakihana Y, Shibata T, Uchida K
  • Organizer: The Society for Redox Biology and Medicine's (SfRBM) 24th Annual Meeting
  • Int'l Joint Research
• [Presentation] 脂質異常症に関連した修飾血清アルブミン構造の解析 (2017)
  • Author(s): 中島史恵、柴田貴広、菊地良介、松下正、内田浩二
  • Organizer: 2017年度生命科学系学会合同年次大会
• [Presentation] Protein carbonyls as a marker of exposome (2017)
  • Author(s): Koji Uchida
  • Organizer: 第 90 回日本細菌学会総会. レドックス・環境応答-国際シンポジウム(新学術領域「酸素生物学」共催) “Stress responses in environmental and exposure biology”
  • Place of Presentation: 仙台国際センター（宮城県仙台市）
  • Int'l Joint Research / Invited
• [Presentation] Natural antibodies as a sensor of oxidation-specific epitopes (2016)
  • Author(s): Koji Uchida
  • Organizer: Shanghai Symposium on Lipid Metabolism and Related Diseases
  • Place of Presentation: Hope Hotel（Shanghai, China)
  • Year and Date: 2016-09-16
  • Int'l Joint Research / Invited
• [Presentation] Electrophiles as a multifunctional molecule (2016)
  • Author(s): Koji Uchida
  • Organizer: 第9回国際NO学会
  • Place of Presentation: 仙台国際センター（宮城県仙台市）
  • Int'l Joint Research / Invited
• [Presentation] 親電子修飾によるタンパク質機能活性化 (2016)
  • Author(s): 内田浩二
  • Organizer: 第89回日本生化学会大会シンポジウム“オルガネラ環境を制御するレドックスシグナル”
  • Place of Presentation: 仙台国際センター（宮城県仙台市）
  • Invited
• [Presentation] リジンピロール化によるDNA様蛋白質の生成 (2015)
  • Author(s): 内田浩二
  • Organizer: 第15回日本蛋白質科学会年会ワークショップ「化学修飾の蛋白質科学と医療への展開」
  • Place of Presentation: あわぎんホール（徳島県徳島市）
  • Invited
• [Presentation] 小分子酸素センサーによるタンパク質カルボニル化 (2015)
  • Author(s): 内田浩二
  • Organizer: 第15回日本蛋白質科学会年会ワークショップ「酸素リモデリング・レドックスシグナルとタンパク質修飾の新たな潮流」
  • Place of Presentation: あわぎんホール（徳島県徳島市）
  • Invited
• [Presentation] ポリフェノールによる自然免疫抗原の生成 (2015)
  • Author(s): 内田浩二
  • Organizer: 第9回日本ポリフェノール学会年次大会シンポジウム「ポリフェノール研究の将来」
  • Place of Presentation: 奈良女子大学（奈良県奈良市）
  • Invited
• [Presentation] 化学的反応性からみる機能性食品成分の潜在能力 (2015)
  • Author(s): 内田浩二
  • Organizer: 第38回日本分子生物学会・第88回日本生学会合同大会ワークショップ「食品科学：食品の潜在能力を科学し、活用する」
  • Place of Presentation: 神戸ポートピアホテル（兵庫県神戸市）
  • Invited
• [Presentation] Pyrrolation Is a Naturally-occurring Covalent Protein Modification Involved in the Production of DNA Mimic Proteins (2014)
  • Author(s): Koji Uchida
  • Organizer: Asian Biological Medicine Summit Forum in Hangzhou
  • Place of Presentation: Hangzhou, China
  • Year and Date: 2014-11-22 – 2014-11-25
  • Invited
• [Presentation] Food-derived natural inhibitors of TLR signaling (2014)
  • Author(s): Koji Uchida
  • Organizer: HNE club/SAS meeting 2014 Lipids, Oxidation, Antioxidants and・・・・・
  • Place of Presentation: Toulouse, France
  • Year and Date: 2014-09-08 – 2014-09-10
  • Invited
• [Presentation] 生体防御反応に関わる機能性食品成分 (2014)
  • Author(s): 内田浩二
  • Organizer: 2014年度 日本生物工学会中部支部例会
  • Place of Presentation: 名古屋大学工学研究科ES総合館（愛知県名古屋市）
  • Year and Date: 2014-08-01
  • Invited
• [Book] Japanese Scientists in Science Signaling 2016「シグナリングに載った日本人研究者」 2017 Issue (2017)
  • Author(s): 西村明幸、西田基宏
  • Total Pages: 80
  • Publisher: Science Signaling AAAS, Cosmo Bio Co. Inc.
• [Book] Innovative Medicine (2015)
  • Author(s): Nishida M, Kuwahara K, Kozai D, Sakaguchi R, Mori Y.
  • Total Pages: 339
  • Publisher: Springer Japan
• [Book] 別冊医学のあゆみ「レドックスUPDATE：ストレス制御の臨床医学・健康科学」 (2015)
  • Author(s): 内田浩二
  • Total Pages: 360
  • Publisher: 医歯薬出版
• [Book] 細胞工学 Vol.34 No.4 (2015)
  • Author(s): 居原秀、大内雄也
  • Total Pages: 440
  • Publisher: 学研メディカル秀潤社
• [Book] 細胞工学 Vol.34 No.4 (2014)
  • Author(s): 熊谷嘉人、内田浩二
  • Total Pages: 440
  • Publisher: 学研メディカル秀潤社