Journal
BIOCHEMICAL PHARMACOLOGY
Volume 90, Issue 2, Pages 135-144Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bcp.2014.04.018
Keywords
Anthocyanin; Apoptosis; Hyperglycemia; Mitochondrial dysfunction; Oxidative stress
Categories
Funding
- National Natural Science Foundation [81372994]
- National Basic Research Program (973 Program) [2012CB517506]
- Foundation for Qualified Personnel in Colleges and Universities in Guangdong Province [2011-128]
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Apoptosis is an early event of steatohepatitis in non-alcoholic fatty liver disease (NAFLD), and an increase in oxidative stress induced by hyperglycemia has been linked to an acceleration of apoptosis in hepatocytes. Cyanidin-3-O-beta-glucoside (C3G), a classic anthocyanin, has been reported to reduce oxidative stress and attenuate non-alcoholic steatohepatitis in mice. In this study, we evaluated the toxicity of high glucose in primary hepatocytes of mice fed with a high fat diet and amelioration of this toxicity by C3G. Incubation of hepatocytes with 35 mM glucose for 12 h resulted in a significant decrease in cell viability and increase in apoptotic cell death. Furthermore, hyperglycemia-induced mitochondrial depolarization was accompanied by the release of cytochrome c and altered expression of Bax and BcI-2, suggesting a mitochondria-mediated apoptotic mode of cell death. Pre-incubation with 50 mu M C3G induced changes associated with better cell survival and function, including a reduction in reactive species generation, improvement of mitochondrial membrane potential, inactivation of caspase-3 and 9, and down-regulation of the pro-apoptotic Bax protein. We further investigated the role of the phosphatidylinositol 3-kinase (PI3K)/Akt and mitogen-activated protein kinases (MAPKs) pathways with respect to the anti-apoptotic action of C3G, and our results showed that C3G could activate Akt. Additionally, C3G inactivated c-Jun N-terminal protein kinase (JNK), but not extracellular signal-regulated kinase or p38 MAPK, in glucose-stressed cells. Interestingly, JNK inhibitor enhanced the protective effect of C3G on cell survival. Our results suggest that anthocyanin C3G may exhibit hepatoprotective potential against NAFLD by promoting functional integrity and survival of hepatocytes. (C) 2014 Elsevier Inc. All rights reserved.
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