RRC ID 73034
Author Otsuka M, Kato N, Taniguchi H, Yoshida H, Goto T, Shiratori Y, Omata M.
Title Hepatitis C virus core protein inhibits apoptosis via enhanced Bcl-xL expression.
Journal Virology
Abstract Previous studies indicated that hepatitis C virus core protein influences cellular apoptosis. However, the precise mechanisms of the effects are not fully understood. Therefore, in this study, we examined the mechanisms of the effects on cell apoptosis by core protein, using transiently transfected and magnetically collected core-producing HepG2 cells. First, to elucidate the target site of core protein in the apoptotic pathway, we examined the activation of caspases after anti-Fas antibody stimulation. Core protein inhibited the apoptotic cascade downstream from caspase 8 and upstream from caspase 3. Next, to clarify more direct mechanisms of this effect, mRNA levels of several bcl-2-related genes were examined. An RNase protection assay showed that the mRNA of bcl-xl increased in the core-producing cells. We showed that this increase was mediated by the enhancement of bcl-x promoter activity by core protein through an extracellular-regulated kinase pathway. These results suggest that core protein inhibits apoptosis at the mitochondria level through augmentation of Bcl-x expression, resulting in an inhibition of caspase 3 activation.
Volume 296(1)
Pages 84-93
Published 2002-4-25
DOI 10.1006/viro.2002.1371
PII S0042682202913711
PMID 12036320
MeSH Apoptosis* Blotting, Western Caspase 3 Caspase 8 Caspase 9 Caspases / analysis Caspases / metabolism Cell Line, Transformed Down-Regulation Enzyme Precursors / metabolism Gene Expression HeLa Cells Hepacivirus / physiology* Humans Liver Proto-Oncogene Proteins c-bcl-2 / analysis Proto-Oncogene Proteins c-bcl-2 / metabolism* RNA, Messenger / analysis Transcriptional Activation Transfection Viral Core Proteins / physiology* bcl-X Protein
IF 2.819
Human and Animal Cells Hep G2 HeLa(RCB0007)