Nongenomic stimulation of nitric oxide release by estrogen is mediated by estrogen receptor α localized in caveolae

Hong Pyo Kim, Jee Young Lee, Jeongmi Kim Jeong, Sung Won Bae, Hong Kyu Lee, Inho Jo

Research output: Contribution to journalArticlepeer-review

263 Scopus citations

Abstract

Acute administration of 17 β-estradiol (E2) exerts antiatherosclerotic effects in healthy postmenopausal women. The vasoprotective action of E2 may be partly accounted for by a rapid increase in nitric oxide (NO) levels in endothelial cells (ECs). However, the signaling mechanisms producing this rise are unknown. In an attempt to address the short-term effect of E2 on endothelial NO production, confluent bovine aortic endothelial cells (BAECs) were incubated in the absence or presence of E2, and NO production was measured. Significant increases in NO levels were detected after only 5 min of E2 exposure without a change in the protein levels of endothelial NO synthase (eNOS). This short-term effect of estrogen was significantly blunted by various ligands which decrease intracellular Ca2+ concentration. Furthermore, plasma membrane-impermeable BSA-conjugated E2 (E2BSA) stimulated endothelial NO release, indicating that in the current system the site of action of E2 is on the plasma membrane rather than the classical nuclear receptor. The partial antagonist tamoxifen did not block E2-induced NO production; however, a pure estrogen receptor α (FRY) antagonist ICI 182,780 completely inhibited E2-stimulated NO release. The binding of E2 to the membrane was confirmed using FITC-labeled E2BSA (E2BSA-FITC). Western blot analysis showed that plasmalemmal caveolae possess ERα in addition to well-known caveolae-associated proteins eNOS and caveolin. This study demonstrates that the nongenomic and short-term effect of E2 on endothelial NO release is Ca2+-dependent and occurs via ERα localized in plasmalemmal caveolae.

Original languageEnglish
Pages (from-to)257-262
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume263
Issue number1
DOIs
StatePublished - 16 Sep 1999

Keywords

  • Caveolae
  • Estrogen
  • Nitric oxide
  • Nitric oxide synthase
  • Nongenomic action

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