Growth Factor Regulation of Interleukin-1β-Induced Nitric Oxide Synthase and GTP: Cyclohydrolase Expression in Cultured Smooth Muscle Cells

• Published in: Biochemical and biophysical research communications Vol. 196; no. 3; pp. 1261 - 1266
• Main Authors: Scottburden, T., Elizondo, E., Ge, T., Boulanger, C.M., Vanhoutte, P.M.
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier Inc 15.11.1993; Elsevier
• Subjects: Amino Acid Oxidoreductases - biosynthesis; Animals; Aorta - drug effects; Aorta - enzymology; Biological and medical sciences; Blotting, Northern; Cell physiology; Cells, Cultured; Fundamental and applied biological sciences. Psychology; Gene Expression - drug effects; Growth Substances - pharmacology; GTP Cyclohydrolase - biosynthesis; Interleukin-1 - pharmacology; Kinetics; Molecular and cellular biology; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - enzymology; Nitric Oxide Synthase; Platelet-Derived Growth Factor - pharmacology; Rats; Responses to growth factors, tumor promotors, other factors; RNA, Messenger - biosynthesis; Transforming Growth Factor beta - pharmacology; Cell culture; Rat; Enzyme; Cytokine; Rodentia; Interleukin 1β; Smooth muscle; Nitric-oxide synthase; Vertebrata; Mammalia; GTP cyclohydrolase I; Hydrolases; Oxidoreductases
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1006/bbrc.1993.2388

Induction of NO synthase expression by interleukin-1β 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-1β-stimulated smooth muscle cells. Peptide growth factors such as fibroblast growth factor, platelet-derived growth factor and transforming growth factorβ1 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.