Suppression of ceramide-induced cell death by hepatitis C virus core protein.
The hepatitis C virus (HCV) core protein is believed to be one of viral proteins that are capable of preventing virus-infected cell death upon various stimuli. But, the effect of the HCV core protein on apoptosis that is induced by various stimuli is contradictory. We examined the possibility that the HCV core protein affects the ceramide-induced cell death in cells expressing the HCV core protein through the sphingomyelin pathway. Cell death that is induced by C(2)-ceramide and bacterial sphingomyelinase was analyzed in 293 cells that constitutively expressed the HCV core protein and compared with 293 cells that were stably transfected only with the expression vector. The HCV core protein inhibited the cell death that was induced by these reagents. The protective effects of the HCV core protein on ceramide-induced cell death were reflected by the reduced expression of p21(WAF1/Cip1/Sid1) and the sustained expression of the Bcl-2 protein in the HCV core-expressing cells with respect to the vector-transfected cells. These results suggest that the HCV core protein in 293 cells plays a role in the modulation of the apoptotic response that is induced by ceramide. Also, the ability of the HCV core protein to suppress apoptosis might have important implications in understanding the pathogenesis of the HCV infection.
Kim
Jung Su
JS
Department of Genetic Engineering, Division of Life Sciences, Hallym University, Chunchon 200-702, Korea.
Ryu
Jiyoon
J
Hwang
Soon Bong
SB
Lee
Soo Young
SY
Choi
Soo Young
SY
Park
Jinseu
J
D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002460:Cell Line; D002470:Cell Survival; D002518:Ceramides / Q000494:pharmacology*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000187:drug effects; D019610:Cytoprotection; D004305:Dose-Response Relationship, Drug; D005822:Genetic Vectors; D016174:Hepacivirus / Q000235:genetics / Q000502:physiology*; D006801:Humans; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013108:Sphingomyelin Phosphodiesterase / Q000494:pharmacology; D013997:Time Factors; D014758:Viral Core Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*
C493956:CDKN1A protein, human; D002518:Ceramides; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D019253:Proto-Oncogene Proteins c-bcl-2; D014758:Viral Core Proteins; D013108:Sphingomyelin Phosphodiesterase