HBV X Gene Impairs Mitochondrial Respiratory Chain By Interacting With Cytochrome C Oxidase Subunit Ⅲ

Background HBx is an essential viral protein that is important for HBV replication and might be a cofactor in the development of hepatocellular carcinoma. However, the exact mechanism of HBx on HCC development is not clarified.Aim Our previous study has found a new HBx-interacted protein COXⅢ. The current study aims to address the role of HBx on COXⅢand mitochondria.Methods We had constructed a recombinant eukaryotic expression plasmid pcDNA3-X and steadily transfected in HL-7702. Thus, we examined the expression of COXⅢ, mitochondrial cytochrome c oxidase activity, mitochondrial membrane potential (ΔΨm), intracellular ROS level. Nuclear transcription factor NF-κB and cell cycle regulator c-Myc are contributed to mediate the pathological effect of HBx in patients with chronic hepatitis, cirrhosis, and liver cancer. We examined the express of NF-?B and c-myc in three groups.Results Our data shows COXⅢmRNA express doesn't change, however, protein expression is down-regulated in HL-7702/HBx. Cytochrome c oxidase activity and mitochondrial membrane potential (ΔΨm) are much lower in HL-7702/HBx compares with other two groups. In despite of this, intracellular ROS level shows no difference between three groups. NF-?B expression displays no change in HL-7702/HBx, while c-myc express is inhibited.Conclusions we assume HBx can down-regulate COXⅢexpress through post-transcriptional level, and impair mitochondrial cytochrome c oxidase activity to induce oxidative stress without increasing ROS level. Activation of NF-κB is ROS independence or NF-κB remains inactive in HL-7702/HBx cell. However, oxidative stress may down-regulate c-myc expression and promote cell enter S phrase and eventually induce apoptosis.