|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
4
|
|
pubmed:dateCreated |
1999-5-20
|
|
pubmed:abstractText |
Previously, we demonstrated that nuclear factor-kappaB (NF-kappaB) mediates cytokine-induced hepatic inducible nitric oxide synthase (iNOS) expression. NF-kappaB activation is regulated by kinases and phosphatases whose function is only beginning to be understood. Therefore, experiments were performed to determine the role of protein phosphatases (PPase) in cytokine-induced iNOS expression. Hepatocytes were stimulated with cytokines in the presence or absence of tyrosine phosphatase inhibitors (pervanadate [PV], phenylarsine oxide [PAO]) and a serine-threonine phosphatase inhibitor (okadaic acid [OA]). Cytokines induced hepatocyte iNOS mRNA, protein, and NO2- production that was substantially decreased by the addition of the tyrosine phosphatase inhibitors (PAO and PV). The serine-threonine phosphatase inhibitor (OA) decreased NO release and protein levels in a concentration-dependent fashion; however, iNOS mRNA levels were not significantly reduced. Nuclear run-on experiments demonstrated that protein tyrosine phosphatases (PTPases) are required for iNOS transcription, while the serine-threonine phosphatase inhibitor (OA) had no effect on iNOS transcription. Electromobility shift assays (EMSAs) revealed that the tyrosine-phosphatase inhibitors blocked cytokine-induced NF-kappaB activation, while OA did not have a significant effect on NF-kappaB DNA binding activity. Therefore, tyrosine phosphatases are involved in the regulation of cytokine-induced activation of NF-kappaB, while serine-threonine phosphatases posttranscriptionally regulate iNOS translation. These results identify the regulatory role of specific protein phosphatases (PPases) in hepatic iNOS expression.
|
|
pubmed:grant |
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cytokines,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/I-kappa B Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappaB inhibitor alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase Type II,
http://linkedlifedata.com/resource/pubmed/chemical/Nos2 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Okadaic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoprotein Phosphatases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Tyrosine Phosphatases,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Apr
|
|
pubmed:issn |
0270-9139
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:volume |
29
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
1199-207
|
|
pubmed:dateRevised |
2007-11-15
|
|
pubmed:meshHeading |
pubmed-meshheading:10094965-Animals,
pubmed-meshheading:10094965-Blotting, Western,
pubmed-meshheading:10094965-Cells, Cultured,
pubmed-meshheading:10094965-Cytokines,
pubmed-meshheading:10094965-DNA,
pubmed-meshheading:10094965-DNA-Binding Proteins,
pubmed-meshheading:10094965-Enzyme Inhibitors,
pubmed-meshheading:10094965-I-kappa B Proteins,
pubmed-meshheading:10094965-Liver,
pubmed-meshheading:10094965-Male,
pubmed-meshheading:10094965-NF-kappa B,
pubmed-meshheading:10094965-Nitric Oxide,
pubmed-meshheading:10094965-Nitric Oxide Synthase,
pubmed-meshheading:10094965-Nitric Oxide Synthase Type II,
pubmed-meshheading:10094965-Okadaic Acid,
pubmed-meshheading:10094965-Phosphoprotein Phosphatases,
pubmed-meshheading:10094965-Phosphorylation,
pubmed-meshheading:10094965-Protein Tyrosine Phosphatases,
pubmed-meshheading:10094965-RNA, Messenger,
pubmed-meshheading:10094965-Rats,
pubmed-meshheading:10094965-Rats, Sprague-Dawley
|
|
pubmed:year |
1999
|
|
pubmed:articleTitle |
The role of protein phosphatases in the expression of inducible nitric oxide synthase in the rat hepatocyte.
|
|
pubmed:affiliation |
Department of Surgery, University of Pittsburgh, Pittsburgh PA, USA. BSTA@med.pitt.edu
|
|
pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|
