Hepatitis B virus X protein induces apoptosis in hepatoma cells through inhibiting Bcl-xL expression.
The X protein of hepatitis B virus (HBx) exhibits numerous activities affecting gene transcription, intracellular signal transduction, cell proliferation and apoptosis. Recent studies showed that HBx induced apoptosis by causing loss of mitochondrial membrane potential, suggesting that HBx-mediated apoptosis is mitochondria-dependent. However, the molecular mechanism of the gene in this pathway is still far from understood. In this study, we demonstrated that introduction of HBx into a hepatocellular carcinoma cell line, Hep3B, caused apoptosis and sensitized the cell to TNFalpha-induced cell killing. Over-expression of Bcl-xL, an anti-apoptotic Bcl-2 family protein, prevented cell death dragged by HBx. Importantly, expression of HBx in Hep3B cells reduced Bcl-xL mRNA and protein levels, but did not regulate other Bcl-2 family members. Although, HBx itself did not affect intracellular distribution of cytochrome c, an enhanced release of cytochrome c from mitochondria was observed when TNFalpha was applied. Thus, the introduction of HBx into Hep3B cells induces apoptosis and sensitizes Hep3B cells to TNFalpha-mediated cell killing, and these processes may accomplish through inhibiting Bcl-xL expression and subsequently promoting cytochrome c release from mitochondria.
Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong SAR.
Ji
J
Miao
George G
GG
Chen
Suk-Ying
SY
Chun
Paul P S
PP
Lai
D017209:Apoptosis; D006528:Carcinoma, Hepatocellular; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology; D012333:RNA, Messenger / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D054334:Viral Regulatory and Accessory Proteins; D051020:bcl-X Protein / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*
D012333:RNA, Messenger; D015534:Trans-Activators; D014409:Tumor Necrosis Factor-alpha; D054334:Viral Regulatory and Accessory Proteins; D051020:bcl-X Protein; C057628:hepatitis B virus X protein; D045304:Cytochromes c