Growth factor regulation of interleukin-1 beta-induced nitric oxide synthase and GTP: cyclohydrolase expression in cultured smooth muscle cells.
Induction of NO synthase expression by interleukin-1 beta in cultured vascular smooth muscle cells from rat aortas was accompanied by simultaneous induction of GTP: cyclohydrolase I. This enzyme regulates the de novo synthesis pathway for tetrahydrobiopterin, an essential cofactor for the catalytic conversion of L-arginine to L-citrulline and NO by inducible NO synthase. Inhibition of GTP: cyclohydrolase attenuated NO production by interleukin-1 beta-stimulated smooth muscle cells. Peptide growth factors such as fibroblast growth factor, platelet-derived growth factor and transforming growth factor beta 1 and the protease thrombin have been shown to modulate the production NO by cytokine-treated smooth muscle cells. These peptide agonists also regulated the induction of NO synthase and GTP: cyclohydrolase mRNA expression.
Scott-Burden
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Center for Experimental Therapeutics, Baylor College of Medicine, Houston, TX 77030.
Elizondo
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Boulanger
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CM
Vanhoutte
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D000594:Amino Acid Oxidoreductases / Q000096:biosynthesis*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000201:enzymology; D015152:Blotting, Northern; D002478:Cells, Cultured; D006136:GTP Cyclohydrolase / Q000096:biosynthesis*; D015870:Gene Expression / Q000187:drug effects*; D006133:Growth Substances / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology*; D007700:Kinetics; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology*; D019001:Nitric Oxide Synthase; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D006133:Growth Substances; D007375:Interleukin-1; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D006136:GTP Cyclohydrolase