Clarifying the molecular mechanism of the Nrf-2 activator carnosic acid in the regulation of the hepatocyte apoptosis

2014 Fiscal Year Final Research Report

• Project/Area Number: 24590992
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Iwate Medical University
• Principal Investigator: WANG TING 岩手医科大学, 医学部, 助教 (70416171)
• Co-Investigator(Renkei-kenkyūsha): TAKIKAWA Yasuhiro 岩手医科大学医学部, 消化器・肝臓内科肝臓分野, 教授 (50254751)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: カルノシン酸 / シグナル / アポトーシス

Outline of Final Research Achievements

Carnosic acid (CA) did not induce the activity of Nrf2 anti-oxidative system in vivo. CA at concentrations as low as 1μM significantly protected against H2O2-induced cytotoxicity and apoptosis of hepatocytes. H2O2 induced phosphorylation of extracellular-signal-regulated kinase 1 and 2 (ERK1/2) in primary hepatocytes. U0126 inhibited the decrease in cell viability induced by H2O2. Co-treatment with CA inhibited ERK1/2 activation induced by H2O2. 4. CA at 1 μM increased protein levels of SIRT1. Pretreatment with EX527 or transfection of SiRNA of SIRT1 weakened the protective effects of CA against H2O2-induced cell death. Our data indicate that CA protects against oxidative stress-induced cytotoxicity via SIRT1 by regulating subsequent downstream factors such as ERK1/2. On the other hand, CA decreased cell viability of human hepatoma Huh 7 and HepG2 cell line in a cell-dependent way. SIRT1/Nrf2 signaling is involved in its function.

Free Research Field

肝臓学