The Involvement of Mitochondrial-related Caspase Pathway in HCV NS5A-induced Apoptosis of Huh-7 Cells

Chronic HCV infection may lead to hepatic fibrosis and the precise mechanisms remain unclear. In this study, Huh-7 cells were transiently transfected with NS5A and subjected to MTT assay, DNA fragmentation assay and western blotting to see the impact of NS5A protein on apoptosis. While cell cycle was not affected, NS5A may inhibit cell proliferation by inducing apoptosis since pro-caspases 3, 8 & 9 were cleaved result in the presence of active forms in a time-dependent fashion. These findings suggested that NS5A-induced apoptosis is caspase-dependent. Furthermore, the cytosolic level of cytochrome c was increased together with a gradually down-regulated Bcl-2 and up-regulated Bax protein expression. The persistent reduction of Bid protein and the gradual increase of tide protein also indicated that a time-dependent increased turn-over of Bid protein into tide. Taken together, our data suggested that HCV NS5A may induce apoptosis through a mitochondrial- related caspase pathway.