Study on molecular mechanisms of glucose metabolic disorders mediated by hepatitis C virus

2014 Fiscal Year Final Research Report

• Project/Area Number: 24590976
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Kobe University
• Principal Investigator: HOTTA Hak 神戸大学, 医学(系)研究科(研究院), 教授 (40116249)
• Co-Investigator(Kenkyū-buntansha): SHOJI Ikuo 神戸大学, 大学院医学研究科, 准教授 (40356241) ; DENG Lin 神戸大学, 大学院医学研究科, 助教 (40437497)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: C型肝炎ウイルス / 感染症 / 糖新生 / Fox01 / 脱リン酸化 / MKP3 / アポトーシス / Bim

Outline of Final Research Achievements

The purpose of this study was to elucidate the molecular mechanism(s) of HCV-mediated activation of the transcription factor FoxO1 that is associated with increased gluconeogenesis and induction of apoptosis through oxidative stress and JNK activation. The results obtained demonstrated that HCV infection induces oxidative stress (production of reactive oxygen species [ROS]) and JNK activation, which leads to increased expression of the phosphatase MKP3 to mediate dephosphorylation (activation) and nuclear localization of FoxO1, thereby promoting gluconeogenesis. Also, HCV-induced oxidative stress and JNK activation lead to increased expression of the pro-apoptotic protein Bim and activation of another pro-apoptotic protein Bax, thereby triggering mitochondrion-mediated apoptosis.

Free Research Field

ウイルス学