Linked Life Data

16897667

Source:http://linkedlifedata.com/resource/pubmed/id/16897667

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2006-8-9
pubmed:abstractText
Patients coinfected with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) have progressive liver disease that frequently leads to cirrhosis and death. We previously showed that hepatocytes exposed to HCV and HIV envelope proteins undergo apoptosis via an innocent-bystander mechanism as a result of the cell surface binding of these proteins, independent of direct viral infection. Here, we have defined the mechanism of this hepatocytic apoptosis. We observed enhanced signal transducer and activator of transcription factor 1 (STAT1) activation and phosphorylation after costimulation with HCV-E2 and HIV-gp120. Moreover, inhibitor studies indicated that Lyn kinase, p38 mitogen-activated protein kinase, and protein kinase C delta might be involved in STAT1 phosphorylation. To elucidate the downstream STAT1-mediated signaling, we overexpressed wild-type STAT1 alpha and the C-terminal domain-deleted mutant STAT1 beta . STAT1 alpha overexpression increased cell apoptosis and Fas ligand expression, compared with STAT1 beta overexpression. STAT1 alpha also enhanced the release of cytochrome c from the mitochondria and caspase-3 activity. These studies indicate that the HCV/HIV envelope proteins cooperatively induce hepatocytic apoptosis by activating a novel downstream STAT1 signaling pathway.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0022-1899
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
194
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
670-81
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Signal transducer and activator of transcription factor 1 mediates apoptosis induced by hepatitis C virus and HIV envelope proteins in hepatocytes.
pubmed:affiliation
Division of Experimental Medicine, Beth Israel Deaconess Medical Center, Harvard Institutes of Medicine, Boston, MA 02115, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural