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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 《American journal of physiology. Cell physiology》2007,293(6):C1953
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 相似文献
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