Nongenomic mechanisms of endothelial nitric oxide synthase activation by the selective estrogen receptor modulator raloxifene

Circulation
T SimonciniJames K Liao

Abstract

Nontranscriptional signaling through estrogen receptors (ERs) is important in the cardiovascular system. In particular, estrogen stimulates endothelial NO synthase (eNOS) via the phosphatidylinositol 3-kinase (PI3K) pathway. The selective estrogen receptor modulator (SERM) raloxifene is effective for the treatment of postmenopausal osteoporosis, but its ability to activate eNOS via PI3K is unknown. Human umbilical vein endothelial cells were cultured in estrogen-deprived, phenol red-free medium. Raloxifene stimulated eNOS in a concentration- and time-dependent manner. Activation of eNOS by raloxifene was blocked by the PI3K inhibitor wortmannin and by the ER antagonist ICI 182,780 but not by transcriptional or translational inhibitors. Coimmunoprecipitation studies demonstrated that, in a ligand-dependent manner, raloxifene increased ERalpha-associated p85alpha, p110alpha, and PI3K activity. This correlated temporally with increases in the serine and threonine phosphorylation and activation of protein kinase Akt. Our findings indicate that nongenomic ER signaling triggered by a SERM leads to a rapid activation of NO synthesis in human endothelial cells. The ability of raloxifene to facilitate ERalpha-PI3K interaction may provid...Continue Reading

References

Oct 24, 1997·Nature·A M BrzozowskiM Carlquist
May 26, 1998·JAMA : the Journal of the American Medical Association·B W WalshP W Anderson
Mar 20, 1999·The Journal of Biological Chemistry·L E Rameh, L C Cantley
Mar 31, 1999·Proceedings of the National Academy of Sciences of the United States of America·L A PaigeD M Fowlkes
Jun 11, 1999·The New England Journal of Medicine·M E Mendelsohn, R H Karas
Jul 29, 1999·Maturitas·A R Genazzani, M Gambacciani
Dec 1, 1999·Endocrinology·A L WijayaratneD P McDonnell
Jun 29, 2000·Current Opinion in Obstetrics & Gynecology·T Simoncini, A R Genazzani
Aug 18, 2000·The Journal of Clinical Endocrinology and Metabolism·T Simoncini, A R Genazzani
Aug 24, 2000·The New England Journal of Medicine·D M HerringtonD Waters

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Citations

Apr 5, 2011·Wiener medizinische Wochenschrift·Vera Regitz-Zagrosek, Ute Seeland
Jul 9, 2009·The Journal of Biological Chemistry·Shokoufeh MahmoodzadehVera Regitz-Zagrosek
Jun 17, 2003·Clinical Obstetrics and Gynecology·Michael W Draper, William W Chin
Jun 30, 2007·Clinical and Experimental Pharmacology & Physiology·Fung Ping LeungYu Huang
Jan 26, 2005·Basic & Clinical Pharmacology & Toxicology·Stefan Nilsson, Konrad F Koehler
Jan 14, 2012·Endocrine Reviews·Elizabeth A TownsendY S Prakash
Feb 12, 2005·Molecular Endocrinology·Ellis R Levin
Dec 17, 2011·Women's Health·Kate Maclaran, John C Stevenson
Oct 30, 2012·European Journal of Gastroenterology & Hepatology·Bin Zhang, Zhi-Yong Wu
Jul 24, 2013·Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology·Levent AkmanMustafa Akin
Apr 25, 2007·Climacteric : the Journal of the International Menopause Society·A CanoJ J Tarín
Jul 12, 2011·Vascular Pharmacology·Matthias R MeyerMatthias Barton
Jun 25, 2009·Molecular and Cellular Endocrinology·Kyung Hee Kim, Jeffrey R Bender
Jun 25, 2008·British Journal of Pharmacology·C M WongY Huang
Jan 31, 2007·Annals of the New York Academy of Sciences·Tommaso SimonciniAndrea Riccardo Genazzani
Oct 27, 2004·Microvascular Research·Hedwig S MurphyRaymond Yung
Apr 28, 2004·Trends in Neurosciences·Matthias EndresMichael A Moskowitz
Nov 23, 2006·European Journal of Pharmacology·Hok Sum LeungYu Huang
May 30, 2006·Maturitas·Martin WehlingRalf Lösel
Mar 18, 2006·Vascular Pharmacology·Chi Ming WongYu Huang
Jun 22, 2005·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Diana AmanteaMaria Tiziana Corasaniti
Aug 11, 2015·Frontiers in Endocrinology·Maria Magdalena Montt-GuevaraTommaso Simoncini
May 3, 2005·Endocrine Journal·Masahide OhmichiYuji Murata
May 14, 2016·Expert Review of Neurotherapeutics·Hidetsugu MaekawaJuha Hernesniemi
Mar 23, 2017·Endocrine Reviews·Nadia BerkaneNathalie Chabbert-Buffet
Aug 26, 2003·Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Médicas E Biológicas·R C TostesM H C Carvalho
Sep 5, 2006·Clinical calcium·Toshio Matsumoto
Feb 20, 2007·Molecular and Cellular Endocrinology·Nélida PoliniVirginia Massheimer
Feb 17, 2005·American Journal of Physiology. Renal Physiology·Fung Ping LeungYu Huang

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