Roles of transsulfuration-mediated cysteine uptake and hydrogen sulfide in liver
| Project/Area Number |
15K08294
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Yamagata University |
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Principal Investigator |
Fujii Junichi 山形大学, 大学院医学系研究科, 教授 (00222258)
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| Co-Investigator(Kenkyū-buntansha) |
倉橋 敏裕 京都府立医科大学, 医学(系)研究科(研究院), 講師 (00596570)
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| Co-Investigator(Renkei-kenkyūsha) |
SATO Hideyo 新潟大学, 医歯学系研究科, 教授 (60235380)
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| Research Collaborator |
HOMMA Takujiro 山形大学, 大学院医学系研究科, 助教 (70743566)
KOBAYASHI Sho 山形大学, 大学院医学系研究科, 助教 (10779490)
LEE Jaeyong 山形大学, 大学院医学系研究科, 大学院生
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | グルタチオン / システイン / 肝障害 / トランススルフィレーション経路 |
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| Outline of Final Research Achievements |
xCT, a cystine transporter, was not expressed in liver of wild-type mice but induced by acetaminophen overdose or under cultivation conditions. Acetaminophen overdose aggravated the xCT-deficient mouse more strongly than the wild-type mouse. While xCT-deficient hepatocytes showed normal phenotype regarding the cysteine-glutathione system, ophthalmic acid accumulated more in the xCT-deficient hepatocytes. These results implied that the transsulfuration pathway plays a central role in supplying cysteine in the liver. When glutathione levels decline, such as the case of elevated oxidative stress, xCT is induced and functions as a backup system to supply cysteine to maintain liver redox homeostasis.
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Report
(4 results)
Research Products
(57 results)
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[Journal Article] The viability of primary hepatocytes in maintained under a low cysteine-glutathione redox state with a marked elevation in ophthalmic acid production.2017
Author(s)
Lee, J., Kang, E. S., Kobayashi, S., Homma, T., Sato, H., Seo, H. G., and Fujii, J.
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Journal Title
Exp. Cell Res.
Volume: 361
Issue: 1
Pages: 178-191
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Decreased reproductive performance in xCT-knockout male mice.2017
Author(s)
Hamashima, S., Homma, T., Kobayashi, S., Ishii, N., Kurahashi, T., Watanabe, R., Kimura, N., Sato, H., and Fujii, J.
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Journal Title
Free Radic. Res.
Volume: 51
Issue: 9-10
Pages: 851-860
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] xCT deficiency aggravates acetaminophen-induced hepatotoxicity under inhibition of the transsulfuration pathway2017
Author(s)
Eun Sil Kang, Jaeyong Lee, Takujiro Homma, Toshihiro Kurahashi, Sho Kobayashi, Atsunori Nabeshima, Sohsuke Yamada, Han GeuK Seo, Satoshi Miyata, Hideyo Sato, Junichi Fujii
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Journal Title
Free Radic Res
Volume: 51
Issue: 1
Pages: 80-90
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Ascorbic acid prevents acetaminophen-induced hepatotoxicity in mice by ameliorating glutathione recovery and autophagy.2016
Author(s)
Kurahashi T, Lee J, Nabeshima A, Homma T, Kang ES, Saito Y, Yamada S, Nakayama T, Yamada K, Miyata S, Fujii J.
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Journal Title
Arch Biochem Biophys
Volume: 604
Pages: 36-46
DOI
Related Report
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Trichloroethylene exposure aggravates behavioral abnormalities in mice that are deficient in superoxide dismutase.2016
Author(s)
Otsuki N, Homma T, Fujiwara H, Kaneko K, Hozumi Y, Shichiri M, Takashima M, Ito J, Konno T, Kurahashi T, Yoshida Y, Goto K, Fujii S, Fujii J.
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Journal Title
Regul Toxicol Pharmacol
Volume: 79
Pages: 83-90
DOI
Related Report
Peer Reviewed
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[Journal Article] Overexpression of Peroxiredoxin 4 Induces Adaptive Intestinal Lipid Metabolism Associated with Suppressive Nonalcoholic Steatohepatitis in a Dietary Mouse Model.2016
Author(s)
Aya Nawata, Hirotsugu Noguchi, Yuichi Mazaki, Toshihiro Kurahashi, Atsunori Nabeshima, Ke-Yong Wang, Satoshi Kimura, Hidetaka Uramoto, Kimitoshi Kohno, Hatsumi Taniguchi, Yoshiya Tanaka, Junichi Fujii, Yasuyuki Sasaguri Toshiyuki Nakayama, and Sohsuke Yamada.
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Journal Title
PLoS One
Volume: e0152549
Issue: 4
Pages: e0152549-e0152549
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Cystathionine is a novel substrate of cystine/glutamate transporter: implications for immune function2015
Author(s)
Kobayashi, S., Sato, M., Kasakoshi, T., Tsutsui, T., Sugimoto, M., Osaki, M., Okada, F., Igarashi, K., Hiratake, J., Homma, T., Conrad, M., Fujii, J., Soga, T., Bannai, S., Sato, H.
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Journal Title
J. Biol. Chem.
Volume: 290
Issue: 14
Pages: 8778-8788
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] On the cysteine supply for glutathione synthesis in the liver under oxidative insult.2015
Author(s)
Junichi Fujii, Toshihiro Kurahashi, Takujiro Homma, Jaeyong Lee, Eun Sil Kang, Shinji Hamashima, Atsunori Nabeshima, Sohsuke Yamada, Toshiyuki Nakayama, and Hideyo Sato.
Organizer
7th Biennial Meeting of Society for Free Radical Research-Asia (SFRR-Asia)
Place of Presentation
Chiang Mai, Thailand
Year and Date
2015-11-29
Related Report
Int'l Joint Research
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