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Proteomic analysis of cell lines expressing small hepatitis B surface antigen revealed decreased glucose‐regulated protein 78 kDa expression in association with higher susceptibility to apoptosis
Author(s) -
Zhao Chao,
Zhang Wei,
Tian Xiaochen,
Fang Caiyun,
Lu Haojie,
Yuan Zhenghong,
Yang Pengyuan,
Wen Yumei
Publication year - 2010
Publication title -
journal of medical virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.782
H-Index - 121
eISSN - 1096-9071
pISSN - 0146-6615
DOI - 10.1002/jmv.21654
Subject(s) - apoptosis , biology , glucose regulated protein , inhibitor of apoptosis domain , microbiology and biotechnology , western blot , hbsag , nucleolin , virology , antigen , cell culture , transferrin receptor , hepatitis b virus , virus , cell , unfolded protein response , programmed cell death , cytoplasm , gene , immunology , genetics , caspase , nucleolus
Accumulating evidence suggests a key role of hepatocyte apoptosis in the pathogenesis of viral hepatitis B. It was found in this study that stable expression of small hepatitis B surface antigen (SHBs) in HepG2 and Huh7 cells increased susceptibility to apoptosis. Proteomic analysis of SHBs expressing HepG2 cells revealed 43 down‐regulated and 38 up‐regulated proteins. Some have been implicated in apoptosis, including glucose‐regulated protein 78 kDa (GRP78), heterogeneous nuclear ribonucleoprotein H3 (hnRNP H), Rho GDP dissociation inhibitor (GDI), cystatin B, far upstream element‐binding protein (FUSEbp), and TNF receptor‐associated protein 1 (TRAP1). Differential expression of GRP78 and several other proteins was confirmed by Western blot analysis. Replenishing GRP78 improved cellular resistance to apoptosis, whereas reduction of GRP78 by siRNA increased susceptibility even in the absence of SHBs. Taken together, these results suggest that HBsAg plays a pro‐apoptotic role through down‐regulation of GRP78. J. Med. Virol. 82:14–22, 2010. © 2009 Wiley‐Liss, Inc.