Hepatitis B virus X protein reduces starvation-induced cell death through activation of autophagy and inhibition of mitochondrial apoptotic pathway
文献类型：期刊论文
| 作者 | Mao, Y; Da, L; Tang, H; Yang, JL; Lei, YR; Tiollais, P; Li, TP; Zhao, MJ |
| 刊名 | BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
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| 出版日期 | 2011 |
| 卷号 | 415期号:1页码:68-74 |
| 关键词 | HBx Cell survival Apoptosis Autophagy Liver cells |
| 通讯作者 | Da, L (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Mol Biol, 320 Yue Yang Rd, Shanghai 200031, Peoples R China.,lda@sibs.ac.cn ; mjzhao@sibs.ac.cn |
| 英文摘要 | The hepatitis B virus X protein (HBx) has been implicated in the development of hepatocellular carcinoma (HCC) associated with chronic infection. As a multifunctional protein, HBx regulates numerous cellular pathways, including autophagy. Although autophagy has been shown to participate in viral DNA replication and envelopment, it remains unclear whether HBx-activated autophagy affects host cell death, which is relevant to both viral pathogenicity and the development of HCC. Here, we showed that enforced expression of HBx can inhibit starvation-induced cell death in hepatic (L02 and Chang) or hepatoma (HepG2 and BEL-7404) cell lines. Starvation-induced cell death was greatly increased in HBX-expressing cell lines treated either with the autophagy inhibitor 3-methyladenine (3-MA) or with an siRNA directed against an autophagy gene, beclin 1. In contrast, treatment of cells with the apoptosis inhibitor Z-Vad-fmk significantly reduced cell death. Our results demonstrate that HBx-mediated cell survival during starvation is dependent on autophagy. We then further investigated the mechanisms of cell death inhibition by HBx. We found that HBx inhibited the activation of caspase-3, an execution caspase, blocked the release of mitochondrial apoptogenic factors, such as cytochrome c and apoptosis-inducing factor (AIF), and inhibited the activation of caspase-9 during starvation. These results demonstrate that HBx reduces cell death through inhibition of mitochondrial apoptotic pathways. Moreover, increased cell viability was also observed in HepG2.2.15 cells that replicate HBV and in cells transfected with HBV genomic DNA. Our findings demonstrate that HBx promotes cell survival during nutrient deprivation through inhibition of apoptosis and activation of autophagy. This highlights an important potential role of autophagy in HBV-infected hepatocytes growing under nutrient-deficient conditions. (C) 2011 Elsevier Inc. All rights reserved. |
| 学科主题 | Biochemistry & Molecular Biology; Biophysics |
| 类目[WOS] | Biochemistry & Molecular Biology ; Biophysics |
| 关键词[WOS] | FAS-MEDIATED APOPTOSIS ; UP-REGULATION ; MECHANISMS ; EXPRESSION ; DISEASE ; CANCER ; DNA |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000297385000012 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/716]  |
| 专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
| 推荐引用方式 GB/T 7714 | Mao, Y,Da, L,Tang, H,et al. Hepatitis B virus X protein reduces starvation-induced cell death through activation of autophagy and inhibition of mitochondrial apoptotic pathway[J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,2011,415(1):68-74. |
| APA | Mao, Y.,Da, L.,Tang, H.,Yang, JL.,Lei, YR.,...&Zhao, MJ.(2011).Hepatitis B virus X protein reduces starvation-induced cell death through activation of autophagy and inhibition of mitochondrial apoptotic pathway.BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,415(1),68-74. |
| MLA | Mao, Y,et al."Hepatitis B virus X protein reduces starvation-induced cell death through activation of autophagy and inhibition of mitochondrial apoptotic pathway".BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 415.1(2011):68-74. |
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