Abstract
This study investigated the effect of exogenous nitric oxide (NO) on endothelial glucocorticoid receptor (GR) function. The NO donor diethylenetriamine NONOate (DETA, 50-500microM) caused concentration dependent nuclear localization of transfected chimeric green fluorescent protein GFP-GR and elevated expression of secreted alkaline phosphatase (SEAP) from a glucocorticoid response element (GRE) promoter construct in bovine aortic endothelial cells. Other weaker NO donors (S-nitroso-N-acetylpenicillamine and spermine NONOate) failed to induce GFP-GR nuclear localization, but all the NO donors activated GRE-SEAP expression, a response unaffected by the antioxidant N-acetyl-L-cysteine. Overall, exogenous NO from high concentration donors can directly activate GR, suggesting a potential feedback mechanism for NO to regulate endothelial inducible nitric oxide synthase (iNOS) expression.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Alkaline Phosphatase / genetics
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Animals
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Aorta / cytology
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Arteries / metabolism
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Cattle
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Cell Nucleus / metabolism
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Dose-Response Relationship, Drug
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Endothelium, Vascular / drug effects*
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Endothelium, Vascular / metabolism*
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Green Fluorescent Proteins
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Humans
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Luminescent Proteins / genetics
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Nitric Oxide / metabolism
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Nitric Oxide / pharmacology*
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Nitric Oxide Donors / pharmacology
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Receptors, Glucocorticoid / genetics
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Receptors, Glucocorticoid / metabolism*
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Response Elements / genetics
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Stress, Mechanical
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Transcription Factors / metabolism
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Transfection
Substances
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Luminescent Proteins
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Nitric Oxide Donors
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Receptors, Glucocorticoid
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Recombinant Fusion Proteins
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Transcription Factors
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Green Fluorescent Proteins
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Nitric Oxide
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Alkaline Phosphatase