Document Detail


Hepatitis C virus NS5A protein protects against TNF-alpha mediated apoptotic cell death.
MedLine Citation:
PMID:  10867196     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Hepatitis C virus (HCV) often causes a prolonged and persistent infection which may lead to hepatocellular carcinoma. We have previously reported that the nonstructural 5A (NS5A) protein of HCV promotes cell growth [Ghosh, A.K., Steele, R., Meyer, K., Ray, R., Ray, R.B., 1999. Hepatitis C virus NS5A protein modulates cell cycle regulatory genes and promotes cell growth. J. Gen. Virol. 80, 1179-1183]. In this study, we investigated the role of HCV NS5A (genotype 1a, strain H) in TNF-alpha induced apoptotic cell death. HepG2 cells expressing NS5A exhibited an inhibitory role in relation to TNF-alpha mediated apoptotic cell death. The NS5A protein blocked the activation of caspase-3 and inhibited proteolytic cleavage of the death substrate poly (ADP-ribose) polymerase in TNF-alpha induced cells. Together, these results suggest that HCV NS5A protein protects against TNF-alpha mediated apoptotic cell death.
Authors:
A K Ghosh; M Majumder; R Steele; K Meyer; R Ray; R B Ray
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Virus research     Volume:  67     ISSN:  0168-1702     ISO Abbreviation:  Virus Res.     Publication Date:  2000 Apr 
Date Detail:
Created Date:  2000-08-09     Completed Date:  2000-08-09     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8410979     Medline TA:  Virus Res     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  173-8     Citation Subset:  IM    
Affiliation:
Department of Pathology, Saint Louis University, St. Louis, MO 63104, USA.
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MeSH Terms
Descriptor/Qualifier:
Blotting, Western
Caspase 3
Caspases / analysis,  metabolism
Cell Death* / drug effects
Cell Line
Dose-Response Relationship, Drug
Hepacivirus / chemistry*
Humans
Microscopy, Confocal
Poly(ADP-ribose) Polymerases
Proteins / analysis,  metabolism
Recombinant Proteins / biosynthesis
Time Factors
Transfection
Tumor Necrosis Factor-alpha / genetics,  pharmacology*
Viral Nonstructural Proteins / biosynthesis,  pharmacology,  physiology*
Grant Support
ID/Acronym/Agency:
R01AI45144/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/NS-5 protein, hepatitis C virus; 0/Proteins; 0/Recombinant Proteins; 0/Tumor Necrosis Factor-alpha; 0/Viral Nonstructural Proteins; EC 2.4.2.30/PARP1 protein, human; EC 2.4.2.30/Poly(ADP-ribose) Polymerases; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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