Vasoinhibins Prevent Bradykinin-Stimulated Endothelial Cell Proliferation by Inactivating eNOS via Reduction of both Intracellular Ca2+ Levels and eNOS Phosphorylation at Ser1179 英文参考文献.docVIP

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Vasoinhibins Prevent Bradykinin-Stimulated Endothelial Cell Proliferation by Inactivating eNOS via Reduction of both Intracellular Ca2+ Levels and eNOS Phosphorylation at Ser1179 英文参考文献.doc

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VasoinhibinsPreventBradykinin-StimulatedEndothelialCellProliferationbyInactivatingeNOSviaReductionofbothIntracellularCa2LevelsandeNOSPhosphorylationatSer1179英文参考文献

Pharmaceuticals 2011, 4, 1052-1069; doi:10.3390/ph4071052 OPEN ACCESS pharmaceuticals ISSN 1424-8247 /journal/pharmaceuticals Article Vasoinhibins Prevent Bradykinin-Stimulated Endothelial Cell Proliferation by Inactivating eNOS via Reduction of both Intracellular Ca2+ Levels and eNOS Phosphorylation at Ser1179 Stéphanie Thebault 1,?,*, Carmen González 1,?, Celina García 1, David Arredondo Zamarripa 1, Gabriel Nava 1, Luis Vaca 2, Fernando López-Casillas 2, Gonzalo Martínez de la Escalera 1 and Carmen Clapp 1 1 Instituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Campus UNAM-Juriquilla, Querétaro 76230, Mexico; E-Mails: cgonzalez.uaslp@ (C.G.); anilec94@ (C.G.); david_arrz@ (D.A.Z.); ganava@ (G.N.); gmel@servidor.unam.mx (G.M.E.); clapp@servidor.unam.mx (C.C.) 2 Instituto de Fisiología Celular, Universidad Nacional Autónoma de México (UNAM), Ciudad Universitaria, Del. Coyoacán, México, D.F., 04510, Mexico; E-Mails: lvaca@ifc.unam.mx (L.V.); fcasilla@ifc.unam.mx (F.L.-C.) ? These authors contributed equally to this work. * Author to whom correspondence should be addressed; E-Mail: stephaniethebault@; Tel.: +52-442-238-1029; Fax: +52-442-238-1005. Received: 29 April 2011; in revised form: 6 July 2011 / Accepted: 19 July 2011 / Published: 20 July 2011 Abstract: Vasoinhibins, a family of antiangiogenic peptides derived from prolactin proteolysis, inhibit the vascular effects of several proangiogenic factors, including bradykinin (BK). Here, we report that vasoinhibins block the BK-induced proliferation of bovine umbilical vein endothelial cells. This effect is mediated by the inactivation of endothelial nitric oxide synthase (eNOS), as the NO donor DETA-NONOate reverted vasoinhibin action. It is an experimentally proven fact that the elevation of intracellular Ca2+ levels ([Ca2+]i) upon BK stimulation activates eNOS, and vasoinhibins blocked the BK-mediated activat