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.
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.
Zhao
Chao
C
Key Laboratory of Medical Molecular Virology, Shanghai Medical College, Institute of Biomedical Sciences, Fudan University, Shanghai, China.
Zhang
Wei
W
Tian
Xiaochen
X
Fang
Caiyun
C
Lu
Haojie
H
Yuan
Zhenghong
Z
Yang
Pengyuan
P
Wen
Yumei
Y
D017209:Apoptosis; D002460:Cell Line; D015536:Down-Regulation / Q000187:drug effects; D000091342:Endoplasmic Reticulum Chaperone BiP; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology*; D006360:Heat-Shock Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D056945:Hep G2 Cells; D006514:Hepatitis B Surface Antigens / Q000235:genetics / Q000378:metabolism*; D006515:Hepatitis B virus / Q000472:pathogenicity*; D022781:Hepatocytes / Q000378:metabolism* / Q000821:virology; D006801:Humans; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D040901:Proteomics; D034741:RNA, Small Interfering
D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D006514:Hepatitis B Surface Antigens; D011506:Proteins; D034741:RNA, Small Interfering; D005947:Glucose