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Article: Genistein enhances relaxation of the spontaneously hypertensive rat aorta by transactivation of epidermal growth factor receptor following binding to membrane estrogen receptors-α and activation of a G protein-coupled, endothelial nitric oxide synthase-dependent pathway

TitleGenistein enhances relaxation of the spontaneously hypertensive rat aorta by transactivation of epidermal growth factor receptor following binding to membrane estrogen receptors-α and activation of a G protein-coupled, endothelial nitric oxide synthase-dependent pathway
Authors
KeywordseNOS
Epidermal growth factor receptor transactivation
G protein activation
Genistein
Membrane estrogen receptor
Issue Date2011
PublisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/issn/10436618
Citation
Pharmacological Research, 2011, v. 63 n. 3, p. 181-189 How to Cite?
AbstractGenistein, a phytoestrogen present in soybeans, has well established vasodilator properties. The present study examined the mechanisms involved in the rapid vascular effects of genistein. Endothelium-dependent relaxations and contractions, induced by acetylcholine and the calcium ionophore A23187, were obtained in isolated aortic rings from male spontaneously hypertensive rats (SHR). Acute exposure to genistein potentiated relaxations and reduced contractions induced by the two agonists. Both effects of genistein were not affected by transcription- and translation-inhibitors or by tyrosine kinase inhibition. The potentiation of acetylcholine and A23187-induced relaxation by genistein was inhibited by NF023 and GP antagonist-2A, selective G i and G q α-subunit antagonists, respectively, but not by NF449, a selective G s α-subunit antagonist. These G protein antagonists did not alter the inhibitory effect of genistein on acetylcholine and A23187-induced contractions. The potentiation of A23187-induced relaxations by genistein was not inhibited by the conventional estrogen receptor (ER) antagonist, ICI 182,780, but inhibited by the specific ER-α antagonist, MPP, and by the epidermal growth factor receptor (EGFR) inhibitor, AG1478. It was mimicked by heparin-binding epidermal growth factor (HB-EGF). Activation of EGFR and endothelial nitric oxide synthase (eNOS) was detected in genistein-treated rings using Western blotting. These data suggest that the rapid vascular actions of genistein are mediated by non-genomic pathways and are unrelated to its tyrosine kinase inhibitory properties. Furthermore, genistein transactivates EGFR through membrane ERα via G protein-coupled pathways. This in turn enhances eNOS phosphorylation and hence endothelial function in the aorta of the SHR. © 2010 Elsevier Ltd.
Persistent Identifierhttp://hdl.handle.net/10722/134728
ISSN
2015 Impact Factor: 4.816
2015 SCImago Journal Rankings: 2.108
ISI Accession Number ID
Funding AgencyGrant Number
Research Grant Council of Hong Kong
Funding Information:

This work was supported by Research Grant Council of Hong Kong.

References

 

DC FieldValueLanguage
dc.contributor.authorLin, AHYen_HK
dc.contributor.authorLeung, GPHen_HK
dc.contributor.authorLeung, SWSen_HK
dc.contributor.authorVanhoutte, PMen_HK
dc.contributor.authorMan, RYKen_HK
dc.date.accessioned2011-07-12T08:22:17Z-
dc.date.available2011-07-12T08:22:17Z-
dc.date.issued2011en_HK
dc.identifier.citationPharmacological Research, 2011, v. 63 n. 3, p. 181-189en_HK
dc.identifier.issn1043-6618en_HK
dc.identifier.urihttp://hdl.handle.net/10722/134728-
dc.description.abstractGenistein, a phytoestrogen present in soybeans, has well established vasodilator properties. The present study examined the mechanisms involved in the rapid vascular effects of genistein. Endothelium-dependent relaxations and contractions, induced by acetylcholine and the calcium ionophore A23187, were obtained in isolated aortic rings from male spontaneously hypertensive rats (SHR). Acute exposure to genistein potentiated relaxations and reduced contractions induced by the two agonists. Both effects of genistein were not affected by transcription- and translation-inhibitors or by tyrosine kinase inhibition. The potentiation of acetylcholine and A23187-induced relaxation by genistein was inhibited by NF023 and GP antagonist-2A, selective G i and G q α-subunit antagonists, respectively, but not by NF449, a selective G s α-subunit antagonist. These G protein antagonists did not alter the inhibitory effect of genistein on acetylcholine and A23187-induced contractions. The potentiation of A23187-induced relaxations by genistein was not inhibited by the conventional estrogen receptor (ER) antagonist, ICI 182,780, but inhibited by the specific ER-α antagonist, MPP, and by the epidermal growth factor receptor (EGFR) inhibitor, AG1478. It was mimicked by heparin-binding epidermal growth factor (HB-EGF). Activation of EGFR and endothelial nitric oxide synthase (eNOS) was detected in genistein-treated rings using Western blotting. These data suggest that the rapid vascular actions of genistein are mediated by non-genomic pathways and are unrelated to its tyrosine kinase inhibitory properties. Furthermore, genistein transactivates EGFR through membrane ERα via G protein-coupled pathways. This in turn enhances eNOS phosphorylation and hence endothelial function in the aorta of the SHR. © 2010 Elsevier Ltd.en_HK
dc.languageeng-
dc.publisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/issn/10436618en_HK
dc.relation.ispartofPharmacological Researchen_HK
dc.subjecteNOSen_HK
dc.subjectEpidermal growth factor receptor transactivationen_HK
dc.subjectG protein activationen_HK
dc.subjectGenisteinen_HK
dc.subjectMembrane estrogen receptoren_HK
dc.titleGenistein enhances relaxation of the spontaneously hypertensive rat aorta by transactivation of epidermal growth factor receptor following binding to membrane estrogen receptors-α and activation of a G protein-coupled, endothelial nitric oxide synthase-dependent pathwayen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1043-6618&volume=63&issue=3&spage=181&epage=189&date=2010&atitle=Genistein+enhances+relaxation+of+the+spontaneously+hypertensive+rat+aorta+by+transactivation+of+epidermal+growth+factor+receptor+following+binding+to+membrane+estrogen+receptors-α+and+activation+of+a+G+protein-coupled,+endothelial+nitric+oxide+synthase-dependent+pathway-
dc.identifier.emailLeung, GPH: gphleung@hkucc.hku.hken_HK
dc.identifier.emailLeung, SWS: swsleung@hku.hken_HK
dc.identifier.emailVanhoutte, PM: vanhoutt@hku.hken_HK
dc.identifier.emailMan, RYK: rykman@hkucc.hku.hken_HK
dc.identifier.authorityLeung, GPH=rp00234en_HK
dc.identifier.authorityLeung, SWS=rp00235en_HK
dc.identifier.authorityVanhoutte, PM=rp00238en_HK
dc.identifier.authorityMan, RYK=rp00236en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.phrs.2010.11.007en_HK
dc.identifier.pmid21111822-
dc.identifier.scopuseid_2-s2.0-79751528958en_HK
dc.identifier.hkuros186081-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-79751528958&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume63en_HK
dc.identifier.issue3en_HK
dc.identifier.spage181en_HK
dc.identifier.epage189en_HK
dc.identifier.eissn1096-1186-
dc.identifier.isiWOS:000288041400004-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridLin, AHY=36999942600en_HK
dc.identifier.scopusauthoridLeung, GPH=35963668200en_HK
dc.identifier.scopusauthoridLeung, SWS=24540419500en_HK
dc.identifier.scopusauthoridVanhoutte, PM=7202304247en_HK
dc.identifier.scopusauthoridMan, RYK=7004986435en_HK
dc.identifier.citeulike8370342-

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