Li L, Hong HH, Chen SP, Ma CQ, Liu HY, Yao YC. Activation of AMPK/MnSOD signaling mediates anti-apoptotic effect of hepatitis B virus in hepatoma cells. World J Gastroenterol 2016; 22(17): 4345-4353 [PMID: 27158203 DOI: 10.3748/wjg.v22.i17.4345]
Corresponding Author of This Article
Ya-Chao Yao, PhD, Department of Clinical Laboratory Medicine, the Second People’s Hospital of Guangdong Province, No. 466 Xinggangzhonglu, Haizhu District, Guangzhou 510317, Guangdong Province, China. yaoyachaoll@163.com
Research Domain of This Article
Cell Biology
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA
Share the Article
Li L, Hong HH, Chen SP, Ma CQ, Liu HY, Yao YC. Activation of AMPK/MnSOD signaling mediates anti-apoptotic effect of hepatitis B virus in hepatoma cells. World J Gastroenterol 2016; 22(17): 4345-4353 [PMID: 27158203 DOI: 10.3748/wjg.v22.i17.4345]
World J Gastroenterol. May 7, 2016; 22(17): 4345-4353 Published online May 7, 2016. doi: 10.3748/wjg.v22.i17.4345
Activation of AMPK/MnSOD signaling mediates anti-apoptotic effect of hepatitis B virus in hepatoma cells
Lei Li, Hong-Hai Hong, Shi-Ping Chen, Cai-Qi Ma, Han-Yan Liu, Ya-Chao Yao
Lei Li, Hong-Hai Hong, Shi-Ping Chen, Han-Yan Liu, Key Laboratory for Major Obstetric Diseases of Guangdong Province, Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, Guangdong Province, China
Cai-Qi Ma, Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China
Ya-Chao Yao, Department of Clinical Laboratory Medicine, the Second People’s Hospital of Guangdong Province, Guangzhou 510317, Guangdong Province, China
Author contributions: Li L, Hong HH and Chen SP contributed equally to this study; Li L, Hong HH and Chen SP carried out the experiments and drafted the manuscript; Ma CQ participated in the experiments; Liu HY analysed the data; Yao YC designed the study and directed its implementation; all authors made critical revisions related to the intellectual content of the manuscript, and approved the final version of the article to be published.
Supported by National Nature Science Foundation of China, No. 81400639 and No. 81502507; The Doctoral Start-up Foundation of Guangzhou Medical University of China, No. 2014C39; The Science Foundation for Youth Scientists of the Second People’s Hospital of Guangdong Province of China, No. YQ2015-002.
Conflict-of-interest statement: To the best of the authors knowledge, all the listed authors have participated actively in the study, and have seen and approved the submitted manuscript. The authors do not have any possible conflicts of interest.
Data sharing statement: No additional unpublished data are available.
Correspondence to: Ya-Chao Yao, PhD, Department of Clinical Laboratory Medicine, the Second People’s Hospital of Guangdong Province, No. 466 Xinggangzhonglu, Haizhu District, Guangzhou 510317, Guangdong Province, China. yaoyachaoll@163.com
Telephone: +86 020 89168136
Received: December 6, 2015 Peer-review started: December 7, 2015 First decision: January 28, 2016 Revised: February 25, 2016 Accepted: March 14, 2016 Article in press: March 14, 2016 Published online: May 7, 2016 Processing time: 145 Days and 6 Hours
Abstract
AIM: To investigate the anti-apoptotic capability of the hepatitis B virus (HBV) in the HepG2 hepatoma cell line and the underlying mechanisms.
METHODS: Cell viability and apoptosis were measured by MTT assay and flow cytometry, respectively. Targeted knockdown of manganese superoxide dismutase (MnSOD), AMP-activated protein kinase (AMPK) and hepatitis B virus X protein (HBx) genes as well as AMPK agonist AICAR and antagonist compound C were employed to determine the correlations of expression of these genes.
RESULTS: HBV markedly protected the hepatoma cells from growth suppression and cell death in the condition of serum deprivation. A decrease of superoxide anion production accompanied with an increase of MnSOD expression and activity was found in HepG2.215 cells. Moreover, AMPK activation contributed to the up-regulation of MnSOD. HBx protein was identified to induce the expression of AMPK and MnSOD.
CONCLUSION: Our results suggest that HBV suppresses mitochondrial superoxide level and exerts an anti-apoptotic effect by activating AMPK/MnSOD signaling pathway, which may provide a novel pharmacological strategy to prevent HCC.
Core tip: Hepatitis B virus markedly protected the cells from growth suppression and cell death in the condition of serum deprivation. A decrease of superoxide anion production accompanied with an increase of manganese superoxide dismutase (MnSOD) expression and activity was found in HepG2.215 cells. Moreover, AMP-activated protein kinase activation contributed to the up-regulation of MnSOD. Hepatitis B virus X protein was identified to promote the expression of AMPK and MnSOD.
