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熊谷嘉人 教授
2017-04-13 10:29   审核人:

一、个人简介

熊谷嘉人,博士, 日本筑波大学医学系,环境生物学实验室

 

二、教育经历

1982   药理学系,学士,日本Fukuoka大学

1984   药理学系,药物代谢和毒理学专业硕士,日本Fukuoka大学

1988   药理学系,药物代谢和毒理学专业博士,日本Fukuoka大学

 

三、工作经历

1989-1992     美国加州大学洛杉矶分校医学院分子药理学系,博士后

1992-1994     日本国立环境研究所,高级研究员

1994-1999     日本筑波大学社会医学研究所,讲师

1999-2003     日本筑波大学社会医学研究所,副教授

2003-2004     日本筑波大学社会医学研究所,教授

2004-2011     日本筑波大学人类科学研究生院,教授

2011-至今     日本筑波大学医学系,环境生物学实验室,教授

2014-至今  全球创新型博士联合培养计划 (GIP-TRIAD),负责人

 

四、研究方向

主要研究能够引起氧化应激的环境亲电子物质(如:多环芳香烃类,甲基汞等)的毒性作用机制,目前研究发现这些物质能够与体内的硫醇(巯基离子)通过化学修饰与蛋白分子相互作用。相关研究能够揭示环境亲电子物质如何影响氧化还原依赖的细胞信号传导和功能发挥,如:细胞存活、 细胞增殖和细胞损伤等机制。我们也有课题涉及活性硫化物 (如硫化氢和硫化物)在氧化还原信号介导的环境亲电子物质的调节中的作用。

 

五、所获荣誉

1990   美国Merck Sharp &Dohme研究室特别研究员奖

2002   日本卫生学会青年研究员奖

2009   日本药理学会专业科学进步奖

2011   日本毒理学会Tanabe

2013   日本药理学会公共卫生专业奖

2013   日本毒理学Pfizer

 

七、文章发表情况(代表性论文

1. Hirose R, Miura T, Sha R, Shinkai Y, Tanaka-Kagawa T, *Kumagai Y. A method for detecting covalent modification of sensor proteins associated with 1,4-naphthoquinone-induced activation of electrophilic signal transduction pathways. Journal of Toxicological Sciences37: 891-898, 2012.

2. Koizumi R, Taguchi K, HisamorMi, *Kumagai Y. Interaction of 9,10- phenanthraquinone with dithiol causes oxidative modification of Cu,Zn-superoxide dismutase (SOD) through redox cycling. Journal of Toxicological Sciences38: 317-324, 2013.

3. Toyama T, Shinkai Y, Kaji T, *Kumagai Y. A convenient method to assess chemical modification of protein thiols by electrophilic metals. Journal of Toxicological Sciences38: 477-484, 2013.

4. Shindo R, Kakehashi H, Okumura K, Kumagai Y, Nakano H. Critical contribution of oxidative stress to TNFα-induced necroptosis downstream of RIPK1 activation. Biochemical Biophysical Research Communications436: 212-216, 2013.

5. Abiko Y, *Kumagai Y. Interaction of Keap1 modified by 2-tert-butyl-1,4-benzoquinone with GSH: Evidence for S-transarylation. Chemical Research in Toxicology26: 1080-1087, 2013.

6. Chang B, Iwamoto N, Inaba T, Shinkai Y, *Kumagai Y. Activation of EGFR/MEK/ERK/AP-1 signaling mediated by 1,2-naphthoquinone, an atmospheric electrophile, in human pulmonary A549 cells. Journal of Toxicological Sciences38: 793-797, 2013.

7. Shinkai Y,Yamanaka I, Duong HHT, Quynh NT, Kanaho Y, *Kumagai Y. Garciniavilersiana bark extract activates the Nrf2/HO-1 signaling pathway in RAW264.7 cells. Journal of Toxicological Sciences38: 875-878, 2013.

8. Asahi M, Kawai M, Toyama T, Kumagai Y, Chuesaard T, Tang N, Kameda T, Hayakawa K, Toriba A. Identification and quantification of in vivo metabolites of 9,10-phenanthrenequinone in human urine associated with producing reactive oxygen species.Chemical Research in Toxicology27: 76-85, 2014.

9. Toyama T, Shinkai Y, Yazawa A, Kakehashi H, Kaji T, *Kumagai Y. Glutathione-mediated reversibility of covalent modification of ubiquitin carboxyl-terminal hydrolase L1 by 1,2-naphthoquinone through Cys152, but not Lys4. Chemical Biological Interactions214: 41-48, 2014.

10. Ida T, Sawa T, Ihara H, Tsuchiya Y, Watanabe Y, Kumagai Y, Suematsu M, Motohashi H, Fujii S, Matsunaga T, Yamamoto M, Ono K, Devarie-Baez NO, Xian M, Fukuto JM, Akaike T. Reactive cysteine persulfides and S-polythiolation regulate oxidative stress and redox signaling. Proceedings of the National Academy of Sciences, USA111: 7606-7611, 2014.

11. Contu VR, Kotake Y, Toyama T, Okuda K, Miyara M, Sakamoto S, Samizo S,Sanoh S,Kumagai Y,Ohta S.Endogenous neurotoxic dopamine derivative covalently binds to Parkinson’s disease-associated ubiquitin C-terminal hydrolase L1 (UCH-L1) and alters its structure and function. Journal of Neurochemistry130: 626-638, 2014.

12. Yoshida E, Abiko Y,*Kumagai Y. Glutathione adduct of methylmercury activates the Keap1-Nrf2 pathway in SH-SY5Y cells. Chemical Research in Toxicology27: 1780-1786, 2014.

13. Makino K, Okuda K, Sugino E, Nishiya T, Toyama T, Iwawaki T, Fujimura M, Kumagai Y, Uehara T. Correlation between attenuation of protein disulfide isomerase activity through S-mercuration and neurotoxicity induced by methylmercury. Neurotoxicology Research27: 99-105, 2014.

14. Shinkai Y, Nakajima S, Eiguren-Fernandez A, Di Stefano E, Schmitz DA, Froines JR, Cho AK, *Kumagai Y. Ambient vapor samples activate the Nrf2-ARE pathway in human bronchial epithelial BEAS-2B cells. Environmental Toxicology29: 1292-1300, 2014.

15. Abiko Y, Mizokawa M, *Kumagai Y. Activation of the Keap1/Nrf2 pathway through covalent modification of the 2-alkenal group of aliphatic electrophiles in Coriandrumsativum L. Journal of Agricultural and Food Chemistry62: 10936-10944,2014.

16. Hagiya Y, Kamata S, Mitsuoka S, Okada N, Yoshida S, Yamamoto J, Ohkubo R, Abiko Y, Yamada H, Akahoshi N, Kasahara T, Kumagai Y, Ishii I. Hemizygosity of transsulfuration genes confers increased vulnerability against acetaminophen-induced hepatotoxicity in mice. Toxicology and Applied Pharmacology282: 195-206, 2015.

17. Nakano S, Ishii I, Shinmura K, Tamaki K, Hishiki T, Akahoshi N, Ida T, Nakanishi T, Kamata S, Kumagai Y, Akaike T, Fukuda K, Sano M, Suematsu M. Hyperhomocysteinemia abrogates fasting-induced cardioprotection against ischemia/reperfusion by limiting bioavailability of hydrogen sulfide anions. Journal of Molecular Medicine93: 879-889, 2015.

18. Shinkai Y, Abiko Y, Ida T, Miura T, Kakehashi H, Ishii I, Nishida M, Sawa T, Akaike T, *Kumagai Y. Reactive sulfur species-mediated activation of the Keap1-Nrf2 pathway by 1,2-napthoquinone through sulfenic acids formation under oxidative stress.Chemical Research in Toxicology28: 838-847, 2015.

19. Abiko Y, Luong C N, *Kumagai Y. A Biotin-PEAC5-maleimide labeling assay to detect electrophiles. Journal of Toxicological Sciences40: 405-411, 2015.

20. Abiko Y, Yoshida E, Ishii I, Fukuto JM, Akaike T,*Kumagai Y. Involvement of reactive persulfides in biological bismethylmercury sulfide formation. Chemical Research in Toxicology28: 1301-1306, 2015.

21. Shinkai Y, Li S, Kikuchi T,*Kumagai Y. Participation of metabolic activation of 2,4,6-trinitrotoluene to 4-hydroxylamino-2,6-dinitrotoluene in the hematotoxicity.Journal of Toxicological Sciences40: 597-604, 2015.

22. Abiko Y, Ishii I, Kamata S, Tsuchiya Y, Watanabe Y, Ihara H, Akaike T, *KumagaiY.Formation of sulfur adducts of N-acetyl-p-benzoquinoneimine, an electrophilic metabolite of acetaminophen in vivo: Participation of reactive persulfides. Chemical Research in Toxicology 28: 1796-1802, 2015.

23. Shinkai Y, Li S, Kikuchi T, Shimojo N, *Kumagai Y. Health survey of workers in a 2,4,6-trinitrotoluene explosives factory in Fuxin, China. Fundamental Toxicological Sciences 2: 171-175, 2015.

24. Ishii I, Kamata S, Hagiya Y, Abiko Y, Kasahara T, Kumagai Y. Protective effects of hydrogen sulfide anions against acetaminophen-induced hepatotoxicity in mice.Journal of Toxicological Sciences40: 837-841, 2015.

25. Abiko Y, Puga A, *Kumagai Y. Covalent binding of quinones activates the Ah receptor in Hepa1c1c7 cells. Journal of Toxicological Sciences40: 873-886, 2015.

26. Toyama T, Abiko Y, Katayama Y, Kaji T, *Kumagai Y. S-Mercuration of ubiquitin C-terminal hydrolase L1 through Cys152 by methylmercury causes inhibition of its catalytic activity and reduction of monoubiquitin levels in SH-SY5Y cells. Journal of Toxicological Sciences40: 887-893, 2015.

27. Saund SS, Sosa V, Henriquez, Nguyen QNN, Soeda S, Bianco CL, Millikin R, White C, Le H, Ono K, Tantillo DJ, Kumagai Y, Akaike T, Lin J, Fukuto JM. The Chemical Biology of Hydropersulfides (RSSH): Chemical Stability, Reactivity and Redox Roles. Archives Biochemistry and Biophysics588: 15-24, 2015.

28. Shinkai Y, Nishihara Y, Amamiya M, Wakayama T, Li S, Kikuch T, Nakai Y, Shimojo N, *Kumagai Y. NADPH-cytochrome P450 reductase-mediated denitration reaction of 2,4,6-trinitrotoluene to yield nitrite in mammals. Free Radical Biology and Medicine91: 178-187, 2016.

29. Shinkai Y, Kimura T, Itagaki A, Yamamoto C, Taguchi K, Yamamoto M, *Kumagai Y, Kaji T. Partial contribution of the Keap1-Nrf2 system to cadmium-mediated metallothionein expression in vascular endothelial cells. Toxicology and Applied Pharmacology295: 37-46, 2016.

30. Fujiwara Y, Yamamoto C, Yoshida E, Kumagai Y, Kaji T. Heparan sulfate chains potentiate cadmium cytotoxicity in cultured vascular endothelial cells. Archives of Toxicology90: 259-267, 2016.


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