Linked Life Data

12065308

Source:http://linkedlifedata.com/resource/pubmed/id/12065308

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2002-6-14
pubmed:abstractText
Nuclear factor-kappaB (NF-kappaB) prevents hepatocytes from undergoing apoptosis during development and liver regeneration. Mice with inactivated glycogen synthase kinase (GSK)-3beta die from hepatocyte apoptosis during development due to a defect in NF-kappaB activation (Hoeflich KP, Luo J, Rubie EA, Tsao MS, Jin O, and Woodgett JR. Nature 406: 86-90, 2000). In this study, we determined the role of GSK-3 in TNF-alpha-induced NF-kappaB activation and cell death in primary hepatocytes. LiCl, an established inhibitor of GSK-3, sensitized primary rat hepatocytes toward TNF-alpha-mediated apoptosis resulting in 90% cell death after 24 h. This was accompanied by increased caspase 8-like and 3-like activities, nuclear fragmentation and DNA laddering. LiCl treatment had no effect on IkappaB-alpha degradation, IkappaB kinase (IKK) activity, NF-kappaB binding activity, and p65 nuclear import and export, but decreased transcription of the NF-kappaB-dependent inducible nitric oxide synthase gene and a NF-kappaB-driven reporter gene. The p65 sequence revealed four potential GSK-3 phosphorylation sites within its COOH-terminal transactivation domains and recombinant GSK-3beta phosphorylated glutathione S-transferase (GST)-p65(354-551), but not GST-p65(1-305) in vitro. These results indicate that GSK-3 protects hepatocytes from TNF-alpha-induced apoptosis through p65 phosphorylation and upregulation of NF-kappaB transactivation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0193-1857
pubmed:author
pubmed:issnType
Print
pubmed:volume
283
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
G204-11
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:12065308-Animals, pubmed-meshheading:12065308-Apoptosis, pubmed-meshheading:12065308-Calcium-Calmodulin-Dependent Protein Kinases, pubmed-meshheading:12065308-Cells, Cultured, pubmed-meshheading:12065308-Glycogen Synthase Kinase 3, pubmed-meshheading:12065308-Glycogen Synthase Kinases, pubmed-meshheading:12065308-Hepatocytes, pubmed-meshheading:12065308-I-kappa B Proteins, pubmed-meshheading:12065308-Lithium Chloride, pubmed-meshheading:12065308-Male, pubmed-meshheading:12065308-NF-kappa B, pubmed-meshheading:12065308-Phosphorylation, pubmed-meshheading:12065308-Rats, pubmed-meshheading:12065308-Rats, Sprague-Dawley, pubmed-meshheading:12065308-Transcription, Genetic, pubmed-meshheading:12065308-Transcription Factor RelA, pubmed-meshheading:12065308-Tumor Necrosis Factor-alpha
pubmed:year
2002
pubmed:articleTitle
Role of glycogen synthase kinase-3 in TNF-alpha-induced NF-kappaB activation and apoptosis in hepatocytes.
pubmed:affiliation
Department of Medicine, Biochemistry, and Biophysics, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.