Estrogen receptor alpha and endothelial nitric oxide synthase are organized into a functional signaling module in caveolae.

K. L. Chambliss, I. S. Yuhanna, C. Mineo, P. Liu, Z. German, T. S. Sherman, M. E. Mendelsohn, R. G. Anderson, P. W. Shaul

Research output: Contribution to journalArticle

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Abstract

Estrogen causes nitric oxide (NO)-dependent vasodilation due to estrogen receptor (ER) alpha-mediated, nongenomic activation of endothelial NO synthase (eNOS). The subcellular site of interaction between ERalpha and eNOS was determined in studies of isolated endothelial cell plasma membranes. Estradiol (E(2), 10(-8) mol/L) caused an increase in eNOS activity in plasma membranes in the absence of added calcium, calmodulin, or eNOS cofactors, which was blocked by ICI 182,780 and ERalpha antibody. Immunoidentification studies detected the same 67-kDa protein in endothelial cell nucleus, cytosol, and plasma membrane. Plasma membranes from COS-7 cells expressing eNOS and ERalpha displayed ER-mediated eNOS stimulation, whereas membranes from cells expressing eNOS alone or ERalpha plus a myristoylation-deficient mutant eNOS were insensitive. Fractionation of endothelial cell plasma membranes revealed ERalpha protein in caveolae, and E(2) caused stimulation of eNOS in isolated caveolae that was ER-dependent; noncaveolae membranes were insensitive. Acetylcholine and bradykinin also activated eNOS in isolated caveolae. Furthermore, the effect of E(2) on eNOS in caveolae was prevented by calcium chelation. Thus, a subpopulation of ERalpha is localized to endothelial cell caveolae where they are coupled to eNOS in a functional signaling module that may regulate the local calcium environment. The full text of this article is available at http://www.circresaha.org.

Original languageEnglish (US)
JournalCirculation Research
Volume87
Issue number11
StatePublished - Nov 24 2000

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Caveolae
Estrogen Receptor alpha
Nitric Oxide Synthase Type III
Nitric Oxide Synthase
Cell Membrane
Endothelial Cells
Calcium
Estrogen Receptors
COS Cells
Bradykinin
Calmodulin
Cell Nucleus
Vasodilation
Cytosol
Acetylcholine
Estradiol
Nitric Oxide
Estrogens
Proteins

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Estrogen receptor alpha and endothelial nitric oxide synthase are organized into a functional signaling module in caveolae. / Chambliss, K. L.; Yuhanna, I. S.; Mineo, C.; Liu, P.; German, Z.; Sherman, T. S.; Mendelsohn, M. E.; Anderson, R. G.; Shaul, P. W.

In: Circulation Research, Vol. 87, No. 11, 24.11.2000.

Research output: Contribution to journalArticle

Chambliss, KL, Yuhanna, IS, Mineo, C, Liu, P, German, Z, Sherman, TS, Mendelsohn, ME, Anderson, RG & Shaul, PW 2000, 'Estrogen receptor alpha and endothelial nitric oxide synthase are organized into a functional signaling module in caveolae.', Circulation Research, vol. 87, no. 11.
Chambliss, K. L. ; Yuhanna, I. S. ; Mineo, C. ; Liu, P. ; German, Z. ; Sherman, T. S. ; Mendelsohn, M. E. ; Anderson, R. G. ; Shaul, P. W. / Estrogen receptor alpha and endothelial nitric oxide synthase are organized into a functional signaling module in caveolae. In: Circulation Research. 2000 ; Vol. 87, No. 11.
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