REGULATION OF BOVINE ENDOTHELIAL CONSTITUTIVE NITRIC-OXIDE SYNTHASE BY OXYGEN

Citation
Jk. Liao et al., REGULATION OF BOVINE ENDOTHELIAL CONSTITUTIVE NITRIC-OXIDE SYNTHASE BY OXYGEN, The Journal of clinical investigation, 96(6), 1995, pp. 2661-2666
Citations number
41
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Medicine, Research & Experimental
ISSN journal
0021-9738
Volume
96
Issue
6
Year of publication
1995
Pages
2661 - 2666
Database
ISI
SICI code
0021-9738(1995)96:6<2661:ROBECN>2.0.ZU;2-G
Abstract
Oxygen (O-2) may regulate pulmonary vascular resistance through change s in endothelial nitric oxide (NO) production. To determine whether co nstitutive NO synthase (cNOS) is regulated by O-2, we assessed cNOS ex pression and activity in bovine pulmonary artery endothelial cells exp osed to different concentrations of O-2. In a time-dependent manner, c hanges in O-2 concentration from 95 to 3% produced a progressive decre ase in cNOS mRNA and protein levels resulting in 4.8- and 4.3-fold red uctions after 24 h, respectively, This correlated with changes in cNOS activity as determined by nitrite measurements, Compared with 20% O-2 , cNOS activity was increased 1.5-fold in 95% O-2 and decreased 1.9-fo ld in 3% O-2. A decrease in O-2 concentration from 95 to 3% shortened cNOS mRNA half-life from 46 to 24 h and caused a 20-fold repression of cNOS gene transcription. Treatment with cycloheximide produced a thre efold increase in cNOS mRNA at all O-2 concentrations, suggesting that cNOS mRNA expression is negatively regulated under basal condition. W e conclude that O-2 upregulates cNOS expression through transcriptiona l and posttranscriptional mechanisms. A decrease in cNOS activity in t he presence of low O-2 levels, therefore, may contribute to hypoxia-in duced vasoconstriction in the pulmonary circulation.