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• W2067203463 endingPage "1207" @default.
• W2067203463 startingPage "1199" @default.
• W2067203463 abstract "Previously, we demonstrated that nuclear factor-κB (NF-κB) mediates cytokine-induced hepatic inducible nitric oxide synthase (iNOS) expression. NF-κB 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 NO 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-κB activation, while OA did not have a significant effect on NF-κB DNA binding activity. Therefore, tyrosine phosphatases are involved in the regulation of cytokine-induced activation of NF-κB, while serine-threonine phosphatases posttranscriptionally regulate iNOS translation. These results identify the regulatory role of specific protein phosphatases (PPases) in hepatic iNOS expression" @default.
• W2067203463 created "2016-06-24" @default.
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• W2067203463 date "1999-04-01" @default.
• W2067203463 modified "2023-10-15" @default.
• W2067203463 title "The role of protein phosphatases in the expression of inducible nitric oxide synthase in the rat hepatocyte" @default.
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• W2067203463 doi "https://doi.org/10.1002/hep.510290419" @default.
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