Hepatitis B Virus X Protein Sensitizes Primary Mouse Hepatocytes to Ethanol- and TNF-α-Induced Apoptosis by a Caspase-3-Dependent Mechanism

It is well-documented that alcohol drinking together with hepatitis viral infection accelerates liver injury; however the underlying mechanisms remain unknown. In this paper, we demonstrated that primary hepatocytes from transgenic mice overexpressing hepatitis B virus X protein (HBX) were more susceptible to ethanol-and TNF-alpha induced apoptotic killing. Compared to normal control mouse hepatocytes, ethanol and/or TNF-a treatment led to a significant increase in reactive oxygen species, mitochondrial permeability transition, cytochrome C release, caspase-3 activity, and poly (ADP-ribose) polymerase degradation in hepatocytes from HBX transgenic mice. Blocking caspase-3 activity antagonized ethanol-and TNF-alpha-induced apoptosis in primary hepatocytes from HBX transgenic mice. Taken together, our findings suggest that HBX sensitizes primary mouse hepatocytes to ethanol-and TNF-alpha-induced apoptosis by a caspase-3-dependent mechanism, which may partly explain the synergistic effects of alcohol consumption and hepatitis B virus infection on liver injury.