Hepatitis B virus X protein reduces starvation-induced cell death through activation of autophagy and inhibition of mitochondrial apoptotic pathway

	Hepatitis B virus X protein reduces starvation-induced cell death through activation of autophagy and inhibition of mitochondrial apoptotic pathway
	Mao, Y; Da, L; Tang, H; Yang, JL; Lei, YR; Tiollais, P; Li, TP; Zhao, MJ
刊名	BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
	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
内容类型	期刊论文
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.