Clarifying the molecular mechanism of the Nrf-2 activator carnosic acid in the regulation of the hepatocyte apoptosis
| Project/Area Number | 24590992 |
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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 |
Gastroenterology
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| Research Institution | Iwate Medical University |
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Principal Investigator |
WANG TING 岩手医科大学, 医学部, 助教 (70416171)
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| 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)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed(Fiscal Year 2014)
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| Budget Amount *help |
¥5,460,000 (Direct Cost : ¥4,200,000、Indirect Cost : ¥1,260,000)
Fiscal Year 2014 : ¥910,000 (Direct Cost : ¥700,000、Indirect Cost : ¥210,000)
Fiscal Year 2013 : ¥1,560,000 (Direct Cost : ¥1,200,000、Indirect Cost : ¥360,000)
Fiscal Year 2012 : ¥2,990,000 (Direct Cost : ¥2,300,000、Indirect Cost : ¥690,000)
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| Keywords | カルノシン酸 / シグナル / アポトーシス / 酸化ストレス / 細胞死 / Carnosic acid / Nrf2 / Oxidative stress |
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| 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.
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Report
(4results)
Research Products
(10results)
