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(Circulation Research. 2002;90:125.)
© 2002 American Heart Association, Inc.

Reports

C/EBP-ß Mediates iNOS Induction by Hypoxia in Rat Pulmonary Microvascular Smooth Muscle Cells

Xingwu Teng, Dechun Li, John D. Catravas, Roger A. Johns

From the Department of Anesthesiology and Critical Care Medicine (X.T., D.L., R.A.J.), Johns Hopkins University School of Medicine, Baltimore, Md; Vascular Biology Center and Department of Pharmacology and Toxicology (J.D.C.), Medical College of Georgia, Augusta, Ga.

Correspondence to Roger A. Johns, MD, Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Blalock 1415, 600 N Wolfe St, Baltimore, MD 21287. E-mail Rajohns{at}jhmi.edu

Abstract

Exposure of rats to 10% O₂ for 4 days caused pulmonary hypertension and induced expression of both inducible nitric oxide synthase (iNOS) and CCAAT box enhancer binding protein-ß (C/EBP-ß) in rat lung. Electrophoretic mobility shift assays (EMSAs) showed that exposure to 1% O₂ increased the C/EBP-ß binding in rat pulmonary microvascular smooth muscle cells (rPSMs). To test the hypothesis that C/EBP-ß participates in hypoxia-induced iNOS expression in rPSMs, a C/EBP motif at -910 bp of rat iNOS promoter was mutated. rPSMs transfected with the rat iNOS promoter and exposed to 1% O₂ for 24 hours had significantly increased wild-type iNOS promoter activity. The hypoxia-induced promoter activity was abolished by the C/EBP motif mutation. Thus, C/EBP-ß mediates, at least in part, hypoxia-induced iNOS expression in rPSMs.

Key Words: inducible nitric oxide synthase • C/EBP-ß • hypoxia • gene regulation • pulmonary hypertension

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