title: Exogenous nitric oxide activates the endothelial glucocorticoid receptor.
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.
authors.affiliation: Department of Bioengineering, Institute for Medicine and Engineering, University of Pennsylvania, 1024 Vagelos Research Laboratory, 3340 Smith Walk, Philadelphia, PA 19104, USA. julieji@seas.upenn.edu
authors.forename: Julie Y
authors.initials: JY
authors.lastname: Ji
authors.forename: Scott L
authors.initials: SL
authors.lastname: Diamond
mesh_terms: D000469:Alkaline Phosphatase / Q000235:genetics; D000818:Animals; D001011:Aorta / Q000166:cytology; D001158:Arteries / Q000378:metabolism; D002417:Cattle; D002467:Cell Nucleus / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism*; D049452:Green Fluorescent Proteins; D006801:Humans; D008164:Luminescent Proteins / Q000235:genetics; D009569:Nitric Oxide / Q000378:metabolism / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D020218:Response Elements / Q000235:genetics; D013314:Stress, Mechanical; D014157:Transcription Factors / Q000378:metabolism; D014162:Transfection
chemical_list: D008164:Luminescent Proteins; D020030:Nitric Oxide Donors; D011965:Receptors, Glucocorticoid; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D049452:Green Fluorescent Proteins; D009569:Nitric Oxide; D000469:Alkaline Phosphatase