Tommaso Simoncini1, Elena Rabkin, James K Liao. 1. Cardiovascular Division, Department of Medicine, Brigham & Women's Hospital and Harvard Medical School, Cambridge, Mass, USA. t.simoncini@obgyn.med.unipi.it
Abstract
OBJECTIVE: Nontranscriptional signaling mechanisms mediate some of the biological effects of estrogen, such as the rapid actions on the blood vessels. By interacting with phosphatidylinositol 3-kinase (PI3K), estrogen receptor (ER) alpha leads to activation of protein kinase Akt and to subsequent increase in endothelial nitric oxide synthase activity. Because PI3K is mainly a cytoplasmic complex, we studied the cellular site of interaction between this enzyme and ERalpha, and we dissected the molecular mechanisms that mediate this interaction. METHODS AND RESULTS: By using cultured human saphenous vain endothelial cells, we found that cell membrane-bound ERalpha colocalizes with PI3K and may be responsible for PI3K activation. Furthermore, we characterized the subsequent steps in the activation of the PI3K/Akt signaling cascade, comparing the molecular events that follow insulin or estradiol activation of PI3K. CONCLUSIONS: We provide novel evidence for an important role of nonnuclear estrogen receptor in rapid, nontranscriptional responses of human endothelial cells to estrogen.
OBJECTIVE: Nontranscriptional signaling mechanisms mediate some of the biological effects of estrogen, such as the rapid actions on the blood vessels. By interacting with phosphatidylinositol 3-kinase (PI3K), estrogen receptor (ER) alpha leads to activation of protein kinase Akt and to subsequent increase in endothelial nitric oxide synthase activity. Because PI3K is mainly a cytoplasmic complex, we studied the cellular site of interaction between this enzyme and ERalpha, and we dissected the molecular mechanisms that mediate this interaction. METHODS AND RESULTS: By using cultured human saphenous vain endothelial cells, we found that cell membrane-bound ERalpha colocalizes with PI3K and may be responsible for PI3K activation. Furthermore, we characterized the subsequent steps in the activation of the PI3K/Akt signaling cascade, comparing the molecular events that follow insulin or estradiol activation of PI3K. CONCLUSIONS: We provide novel evidence for an important role of nonnuclear estrogen receptor in rapid, nontranscriptional responses of human endothelial cells to estrogen.
Authors: Ana Navarro; Eva Del Valle; Cristina Ordóñez; Eva Martínez; Cristina Pérez; Ana Alonso; Celestino González; Jorge Tolivia Journal: Age (Dordr) Date: 2012-05-10
Authors: Whitney Wharton; Carey E Gleason; Katelin R Lorenze; Tamara S Markgraf; Michele L Ries; Cynthia M Carlsson; Sanjay Asthana Journal: Am J Transl Res Date: 2009-01-20 Impact factor: 4.060
Authors: Robert X Song; Christopher J Barnes; Zhenguo Zhang; Yongde Bao; Rakesh Kumar; Richard J Santen Journal: Proc Natl Acad Sci U S A Date: 2004-02-05 Impact factor: 11.205
Authors: Amanda J LeBlanc; Rafael Reyes; Lori S Kang; Robert A Dailey; John N Stallone; Natasha C Moningka; Judy M Muller-Delp Journal: Am J Physiol Regul Integr Comp Physiol Date: 2009-10-07 Impact factor: 3.619