Nitric oxide stimulates stress-activated protein kinases in glomerular endothelial and mesangial cells.
Exposure of rat glomerular mesangial cells and primary cultures of bovine glomerular endothelial cells to compounds releasing nitric oxide (NO), including MAHMA-NONOate, S-nitrosoglutathione, and spermine-NO, results in a time- and concentration-dependent activation of stress-activated protein kinases (SAPK) as measured by the phosphorylation of c-Jun in a solid phase kinase assay. Dibutyryl cGMP had no effect on SAPK activity. Pretreatment of the cells with the tyrosine kinase inhibitor genistein strongly attenuated NO-induced c-Jun phosphorylation. Furthermore, N-acetylcysteine markedly reduced the activation of SAPK in response to NO. These studies identify SAPK as a target for NO which may be critical for the NO-induced apoptosis of glomerular mesangial and endothelial cells.
Department of Pharmacology, Biozentrum, University of Basel, Switzerland.
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Pfeilschifter
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Huwiler
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000276:immunology / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D004727:Endothelium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D019833:Genistein; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005978:Glutathione / Q000031:analogs & derivatives / Q000494:pharmacology; D007527:Isoenzymes; D007529:Isoflavones / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases; D007678:Kidney Glomerulus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D020928:Mitogen-Activated Protein Kinases; D009569:Nitric Oxide / Q000494:pharmacology*; D009589:Nitrogen Oxides; D009603:Nitroso Compounds / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D026422:S-Nitrosoglutathione; D015398:Signal Transduction; D013096:Spermine / Q000031:analogs & derivatives / Q000494:pharmacology
D004791:Enzyme Inhibitors; D007527:Isoenzymes; D007529:Isoflavones; D009589:Nitrogen Oxides; D009603:Nitroso Compounds; C091861:spermine nitric oxide complex; D013096:Spermine; D009569:Nitric Oxide; D026422:S-Nitrosoglutathione; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D005978:Glutathione