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

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

doi:10.1161/hh0202.103647

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

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

School of Medicine

Research output: Contribution to journal › Article › peer-review

29 Scopus citations

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-β (C/EBP-β) in rat lung. Electrophoretic mobility shift assays (EMSAs) showed that exposure to 1% O₂ increased the C/EBP-β binding in rat pulmonary microvascular smooth muscle cells (rPSMs). To test the hypothesis that C/EBP-β 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-β mediates, at least in part, hypoxia-induced iNOS expression in rPSMs.

Original language	English (US)
Pages (from-to)	125-127
Number of pages	3
Journal	Circulation research
Volume	90
Issue number	2
DOIs	https://doi.org/10.1161/hh0202.103647
State	Published - Feb 8 2002

Keywords

C/EBP-β
Gene regulation
Hypoxia
Inducible nitric oxide synthase
Pulmonary hypertension

ASJC Scopus subject areas

Physiology
Cardiology and Cardiovascular Medicine

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

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-β (C/EBP-β) in rat lung. Electrophoretic mobility shift assays (EMSAs) showed that exposure to 1% O2 increased the C/EBP-β binding in rat pulmonary microvascular smooth muscle cells (rPSMs). To test the hypothesis that C/EBP-β 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-β mediates, at least in part, hypoxia-induced iNOS expression in rPSMs.",

keywords = "C/EBP-β, Gene regulation, Hypoxia, Inducible nitric oxide synthase, Pulmonary hypertension",

author = "Xingwu Teng and Dechun Li and Catravas, {John D.} and Johns, {Roger A.}",

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doi = "10.1161/hh0202.103647",

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T1 - C/EBP-β mediates iNOS induction by hypoxia in rat pulmonary microvascular smooth muscle cells

AU - Teng, Xingwu

AU - Li, Dechun

AU - Catravas, John D.

AU - Johns, Roger A.

PY - 2002/2/8

Y1 - 2002/2/8

N2 - 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-β (C/EBP-β) in rat lung. Electrophoretic mobility shift assays (EMSAs) showed that exposure to 1% O2 increased the C/EBP-β binding in rat pulmonary microvascular smooth muscle cells (rPSMs). To test the hypothesis that C/EBP-β 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-β mediates, at least in part, hypoxia-induced iNOS expression in rPSMs.

AB - 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-β (C/EBP-β) in rat lung. Electrophoretic mobility shift assays (EMSAs) showed that exposure to 1% O2 increased the C/EBP-β binding in rat pulmonary microvascular smooth muscle cells (rPSMs). To test the hypothesis that C/EBP-β 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-β mediates, at least in part, hypoxia-induced iNOS expression in rPSMs.

KW - C/EBP-β

KW - Gene regulation

KW - Hypoxia

KW - Inducible nitric oxide synthase

KW - Pulmonary hypertension

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

Abstract

Keywords

ASJC Scopus subject areas

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