C/EBP-β mediates iNOS induction by hypoxia in rat pulmonary microvascular smooth muscle cells

被引:28
作者
Teng, XW
Li, DC
Catravas, JD
Johns, RA
机构
[1] Johns Hopkins Univ, Sch Med, Dept Anesthesiol & Crit Care Med, Baltimore, MD 21287 USA
[2] Med Coll Georgia, Vasc Biol Ctr, Augsburg, Germany
[3] Med Coll Georgia, Dept Pharmacol & Toxicol, Augsburg, Germany
关键词
D O I
10.1161/hh0202.103647
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Exposure of rats to 10% O-2 for 4 days caused pulmonary hypertension and induced expression of both inducible nitric oxide synthase (iNOS) and CCAAT box enhancer binding protein-beta (C/EBP-beta) in rat lung. Electrophoretic mobility shift assays (EMSAs) showed that exposure to 1% O-2 increased the C/EBP-beta binding in rat pulmonary microvascular smooth muscle cells (rPSMs). To test the hypothesis that C/EBP-beta participates in hypoxia-induced iNOS expression in rPSMs, a C/EBP motif at -910 by of rat iNOS promoter was mutated. rPSMs transfected with the rat iNOS promoter and exposed to 1% O-2 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-beta mediates, at least in part, hypoxia-induced iNOS expression in rPSMs.
引用
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页码:125 / 127
页数:3
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