title: Hepatitis C virus core protein inhibits apoptosis via enhanced Bcl-xL expression.
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.
authors.affiliation: Department of Gastroenterology, University of Tokyo, Tokyo, Japan.
authors.forename: Motoyuki
authors.initials: M
authors.lastname: Otsuka
authors.forename: Naoya
authors.initials: N
authors.lastname: Kato
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Taniguchi
authors.forename: Hideo
authors.initials: H
authors.lastname: Yoshida
authors.forename: Tadashi
authors.initials: T
authors.lastname: Goto
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Shiratori
authors.forename: Masao
authors.initials: M
authors.lastname: Omata
mesh_terms: D017209:Apoptosis; D015153:Blotting, Western; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000032:analysis / Q000378:metabolism; D002461:Cell Line, Transformed; D015536:Down-Regulation; D004792:Enzyme Precursors / Q000378:metabolism; D015870:Gene Expression; D006367:HeLa Cells; D016174:Hepacivirus / Q000502:physiology*; D006801:Humans; D008099:Liver; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D015533:Transcriptional Activation; D014162:Transfection; D014758:Viral Core Proteins / Q000502:physiology*; D051020:bcl-X Protein
chemical_list: C494811:BCL2L1 protein, human; D004792:Enzyme Precursors; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D014758:Viral Core Proteins; D051020:bcl-X Protein; C069130:nucleocapsid protein, Hepatitis C virus; C505407:CASP3 protein, human; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases