Roles of transsulfuration-mediated cysteine uptake and hydrogen sulfide in liver

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K08294
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: Yamagata University
• Principal Investigator: Fujii Junichi 山形大学, 大学院医学系研究科, 教授 (00222258)
• 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)
• Co-Investigator(Renkei-kenkyūsha): SATO Hideyo 新潟大学, 医歯学系研究科, 教授 (60235380)
• 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
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: グルタチオン / システイン / 肝障害

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.

Free Research Field

生化学分子生物学