To better study the role of HCV core protein in hepatic lipid accumulation, we established Chang liver
PCI32765 having stable expression of HCV core191 protein. The expression of HCV core mRNA and protein were confirmed by RT-PCR and immunoblotting, respectively (data not shown). To examine the effect of HCV core protein on the lipid accumulation, Chang-core stable cells and parent Chang live cells were stained with Oil-Red O (ORO). The percentage of ORO-positive cells among Chang liver cells stably expressing HCV core protein was significantly higher than in parent Chang liver cells (data not shown). Because SREBP1 has been shown to play a critical role for hepatic lipid accumulation, we investigated the effect of HCV core protein on the gene expression of SREBP1. We observed that HCV core protein increases the expression of SREBP1 mRNA or premature/mature SREBP1 (pSREBP1/mSREBP1) protein in Chang-core191 stable
cells (Fig. 1A) and transiently transfected Chang liver cells (Fig. 1B and C). It is reported that mature HCV core protein (C-terminal truncated, 173 aa) is the major form present in the native viral particles together full length core protein (191 aa) [16]. We examined whether mature core protein also modulates the gene expression of SREBP1. As shown in Fig. 1B and C, the truncated core protein also induced the transcription of SREBP1 gene in Chang liver cells. This enhancement by the core protein was also observed in HepG2 and Huh7 (data not shown). Thus, these results indicate that HCV core protein elevates the mRNA and protein expression of SREBP1.
