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Phytoestrogen Genistein Up-Regulates Endothelial Nitric Oxide Synthase Expression Via Activation of cAMP Response Element-Binding Protein in Human Aortic Endothelial Cells

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dc.contributor.authorSi, Hongweien
dc.contributor.authorYu, Jieen
dc.contributor.authorJiang, Honglinen
dc.contributor.authorLum, Hazelen
dc.contributor.authorLiu, Dongminen
dc.contributor.departmentAnimal and Poultry Sciencesen
dc.contributor.departmentHuman Nutrition, Foods, and Exerciseen
dc.date.accessed2014-07-07en
dc.date.accessioned2014-07-08T13:02:18Zen
dc.date.available2014-07-08T13:02:18Zen
dc.date.issued2012-07en
dc.description.abstractWe previously reported that genistein, a phytoestrogen, up-regulates endothelial nitric oxide synthase (eNOS) and prevents hypertension in rats that are independent of estrogen signaling machinery. However, how genistein regulates eNOS expression is unknown. In the present study, we show that genistein enhanced eNOS expression and NO synthesis in primary human aortic endothelial cells. Inhibition of extracellular signal regulated kinase, phosphoinositol-3 kinase, or protein kinase C did not affect genistein-enhanced eNOS expression and NO synthesis. However, chemical inhibition of protein kinase A (PKA) or adenoviral transfer of the specific endogenous PKA inhibitor gene completely abolished PKA activity and genistein-stimulated eNOS expression and NO production. Accordingly, genistein induced PKA activity and subsequent phosphorylation of cAMP response element (CRE)-binding protein (CREB) at Ser133. Suppression of CREB by small interfering RNA transfection abolished genistein-enhanced eNOS expression and NO production. Consistently, deletion of the CRE site within human eNOS promoter eliminated genistein-stimulated eNOS promoter activity. These findings provide the first evidence to our knowledge that genistein may play a beneficial role in vascular function through targeting the PKA/CREB/eNOS/NO signaling pathway. (Endocrinology 153: 3190-3198, 2012)en
dc.description.sponsorshipNational Center for Complementary and Alternative Medicine of National Institutes of Health 1R21AT002739, 1R21AT004694-01, 1R21AT004694S1en
dc.description.sponsorshipAmerican Heart Association Mid-Atlanticen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationHongwei Si, Jie Yu, Hongling Jiang, Hazel Lum, and Dongmin Liu. "Phytoestrogen Genistein Up-Regulates Endothelial Nitric Oxide Synthase Expression Via Activation of cAMP Response Element-Binding Protein in Human Aortic Endothelial Cells," Endocrinology 2012 153:7, 3190-3198. DOI: http://dx.doi.org/10.1210/en.2012-1076en
dc.identifier.doihttps://doi.org/10.1210/en.2012-1076en
dc.identifier.issn0013-7227en
dc.identifier.urihttp://hdl.handle.net/10919/49395en
dc.identifier.urlhttp://press.endocrine.org/doi/abs/10.1210/en.2012-1076en
dc.language.isoenen
dc.publisherEndocrine Societyen
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subjectenos gene-expressionen
dc.subjectkinase-cen
dc.subjectpostmenopausal womenen
dc.subjectsoy isoflavonesen
dc.subjectmolecular-cloningen
dc.subjectcoupled receptoren
dc.subjectblood-pressureen
dc.subjectplasma-lipidsen
dc.subjectnoen
dc.subjectsynthaseen
dc.subjectestrogenen
dc.subjectendocrinology & metabolismen
dc.titlePhytoestrogen Genistein Up-Regulates Endothelial Nitric Oxide Synthase Expression Via Activation of cAMP Response Element-Binding Protein in Human Aortic Endothelial Cellsen
dc.title.serialEndocrinologyen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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