Endothelin stimulates prostaglandin endoperoxide synthase-2 mRNA expression and protein synthesis through a tyrosine kinase-signaling pathway in rat mesangial cells.
We evaluated the role of endothelin-1 (ET-1), a vasoconstrictor peptide, to regulate prostaglandin endoperoxide synthase (PGHS)-1 and -2 gene expression and protein synthesis in cultured rat mesangial cells (MC). ET-1 induced mRNA for PGHS-2 but not PGHS-1 and also stimulated protein accumulation of PGHS-2 but not PGHS-1 in MC. ET-1 induction of PGHS-2 protein was accompanied by a sustained enhancement of enzymatic activity assessed by conversion of arachidonic acid to prostaglandin E2. The ET-1-stimulated PGHS-2 expression was reduced with protein tyrosine kinase but not with protein kinase C inhibitors or in protein kinase C-depleted cells. Both dexamethasone and heparin reduced ET-1-activated PGHS-2 mRNA expression and protein formation. We conclude that in MC, ET-1 induces PGHS-2 through a protein tyrosine kinase-dependent pathway.
Kester
M
M
Department of Medicine, Case Western Reserve University, School of Medicine, Cleveland, Ohio 44106.
Coroneos
E
E
Thomas
P J
PJ
Dunn
M J
MJ
D000818:Animals; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D016232:Endothelins / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D005920:Glomerular Mesangium / Q000187:drug effects / Q000201:enzymology*; D006493:Heparin / Q000494:pharmacology; D007527:Isoenzymes / Q000096:biosynthesis*; D007700:Kinetics; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D014176:Protein Biosynthesis / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects
D016232:Endothelins; D007527:Isoenzymes; D012333:RNA, Messenger; D003609:Dactinomycin; D003907:Dexamethasone; D006493:Heparin; D003513:Cycloheximide; D011451:Prostaglandin-Endoperoxide Synthases