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Effect of caveolin-1 scaffolding peptide and 17[beta]-estradiol on intracellular [Ca.sup.2+] kinetics evoked by angiotensin II in human vascular smooth muscle cells

Authors :
Mendez-Bolaina, Enrique
Sanchez-Gonzalez, Javier
Ramirez-Sanchez, Israel
Ocharan-Hernandez, Esther
Nunez-Sanchez, Marisol
Meaney-Mendiolea, Eduardo
Meaney, Alejandra
Asbun-Bojalil, Juan
Miliar-Garcia, Angel
Olivares- Corichi, Ivonne
Ceballos-Reyes, Guillermo
Source :
The American Journal of Physiology. Dec, 2007, Vol. 293 Issue 6, pC1953, 9 p.
Publication Year :
2007

Abstract

Caveolae are identifiable plasma membrane invaginations. The main structural proteins of caveolae are the caveolins. There are three caveolins expressed in mammals, designated Cav-1, Cav-2, and Cav-3. It has been postulated that Cav-1 acts as a scaffold protein for signaling proteins; these include ion channels, enzymes, and other ligand receptors like membrane-associated estrogen receptor (ER)[alpha] or ER[beta]. Caveolae-associated membrane proteins are involved in regulating some of the rapid estrogenic effects of 17[beta]-estradiol. One important system related to the activity of ER[alpha] and caveolae is the renin-angiotensin system. Angiotensin II (ANG II) has numerous actions in vascular smooth muscle, including modulation of vasomotor tone, cell growth, apoptosis, phosphatidylinositol 3-kinase (PI3K)/Akt activation, and others. Many proteins associated with caveolae are in close relation with the scaffolding domain of Cav-1 (82-101 amino acid residues). It has been proposed that this peptide may acts as a kinase inhibitor. Therefore, to explore the ability of Cav-1 scaffolding peptide (CSP-1) to regulate ANG 1I function and analyze the relationship between ER[alpha] and ANG II type 1 and 2 ([AT.sub.1] and [AT.sub.2]) receptors, we decided to study the effects of CSP-1 on ANG H-induced intracellular [Ca.sup.2+] kinetics and the effect of 17[beta]-estradiol on this modulation using human smooth muscle cells in culture, intracellular [Ca.sup.2+] concentration measurements, immuno- and double-immunocytochemistry confocal analysis of receptor expression, immunoblot analysis, and immunocoprecipitalion assays to demonstrate coexpression. We hypothesized that CSP-1 inhibits ANG II-mediated increases in intracellular [Ca.sup.2+] concentrations by interfering with intracellular signaling including the PI3K/Akt pathway. We also hypothesize that ATE receptors associate with Cav-1. Our results show that there is a close association of [AT.sub.1], [AT.sub.2], and [ER.sub.[alpha]] with Cav-1 in human medal smooth muscle cells in culture. CSP-1 inhibits ANG II-induced intracellular signaling. estrogen receptors; angiotensin type 1 and 2 receptors; phosphatidylinositol 3-kinase; intracellular signaling; tissue culture; angiotensin receptors

Details

Language :
English
ISSN :
00029513
Volume :
293
Issue :
6
Database :
Gale General OneFile
Journal :
The American Journal of Physiology
Publication Type :
Academic Journal
Accession number :
edsgcl.172832757