HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 293/6/C1953    most recent 00519.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Méndez-Bolaina, E. Articles by Ceballos-Reyes, G. Search for Related Content PubMed PubMed Citation Articles by Méndez-Bolaina, E. Articles by Ceballos-Reyes, G.

RECEPTORS AND SIGNAL TRANSDUCTION

Effect of caveolin-1 scaffolding peptide and 17β-estradiol on intracellular Ca²⁺ kinetics evoked by angiotensin II in human vascular smooth muscle cells

¹Laboratorio Multidisciplinario, Sección de Posgrado, Escuela Superior de Medicina, Instituto Politécnico Nacional, México City, México; ²Facultad de Ciencias Químicas, Universidad Veracruzana, Orizaba, Veracruz; ³Departamento de Biología Celular y Tisular, Escuela Médico Militar-Universidad de Falcón, México City; ⁴Unidad de Investigación Médica en Genética Humana, Hospital de Pediatría, Centro Médico Nacional Siglo XXI-IMSS, México City; and ⁵Unidad Cardiovascular del Hospital Regional 1°, De Octubre, Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado, México City, México

Submitted 5 October 2006 ; accepted in final form 11 October 2007

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) or ERβ. Caveolae-associated membrane proteins are involved in regulating some of the rapid estrogenic effects of 17β-estradiol. One important system related to the activity of ER 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 II function and analyze the relationship between ER and ANG II type 1 and 2 (AT₁ and AT₂) receptors, we decided to study the effects of CSP-1 on ANG II-induced intracellular Ca²⁺ kinetics and the effect of 17β-estradiol on this modulation using human smooth muscle cells in culture, intracellular Ca²⁺ concentration measurements, immuno- and double-immunocytochemistry confocal analysis of receptor expression, immunoblot analysis, and immunocoprecipitation assays to demonstrate coexpression. We hypothesized that CSP-1 inhibits ANG II-mediated increases in intracellular Ca²⁺ concentrations by interfering with intracellular signaling including the PI3K/Akt pathway. We also hypothesize that AT₂ receptors associate with Cav-1. Our results show that there is a close association of AT₁, AT₂, and ER with Cav-1 in human arterial 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