Caveolin-1 regulates contractility in differentiated vascular smooth muscle

Abstract

. Caveolin-1 regulates contractility in differentiated vascular smooth muscle. Am J Physiol Heart Circ Physiol 286: H91-H98, 2004. First published September 11, 2003 10.1152/ajpheart.00472.2003.-Caveolin is a principal component of caveolar membranes. In the present study, we utilized a decoy peptide approach to define the degree of involvement of caveolin in PKCdependent regulation of contractility of differentiated vascular smooth muscle. The primary isoform of caveolin in ferret aorta vascular smooth muscle is caveolin-1. Chemical loading of contractile vascular smooth muscle tissue with a synthetic caveolin-1 scaffolding domain peptide inhibited PKC-dependent increases in contractility induced by a phorbol ester or an ␣ agonist. Peptide loading also resulted in a significant inhibition of phorbol ester-induced adducin Ser 662 phosphorylation, an intracellular monitor of PKC kinase activity, ERK1/2 activation, and Ser 789 phosphorylation of the actin binding protein caldesmon. ␣-Agonist-induced ERK1-1/2 activation was also inhibited by the caveolin-1 peptide. Scrambled peptide-loaded tissues or sham-loaded tissues were unaffected with respect to both contractility and signaling. Depolarization-induced activation of contraction was not affected by caveolin peptide loading. Similar results with respect to contractility and ERK1/2 activation during exposure to the phorbol ester or the ␣-agonist were obtained with the cholesterol-depleting agent methyl-␤-cyclodextrin. These results are consistent with a role for caveolin-1 in the coordination of signaling leading to the regulation of contractility of smooth muscle.

New Insights into 4-Amino-2-tri-fluoromethyl-phenyl Ester Inhibition of Cell Growth and Migration in the A549 Lung Adenocarcinoma Cell Line

“…While caveolae is familiar to be as petty as 50 nm in diameter, well below the limit of resolution of the Immunofluorescence, these punctate spots were consistently observed. The same punctate spots have been reported before (Je et al, 2004). It has already been proved to be clustering of caveolae in electron micrographs (Isshiki et al, 2002).…”

Dynamic Association of Nitric Oxide Downstream Signaling Molecules with Endothelial Caveolin-1 in Rat Aorta

“…Some agonists causing contraction of vascular smooth muscle act on receptors that are believed to be located in caveolae or to aggregate in caveolae upon ligand binding (Chun et al, 1994;de Weerd and Leeb-Lundberg, 1997;Ishizaka et al, 1998;Je et al, 2004). We observed in this study that methyl-␤-cyclodextrin did not change smooth muscle contractile responses to phenylephrine, indicating that this ␣-adrenergic agonist does not require signaling molecules in cholesterol-rich domains to cause contraction.…”

“…Cyclodextrin, a water-soluble cyclic oligosaccharide formed of seven glucopyranose units able to accept one molecule of cholesterol in its hydrophobic core, is a membrane-impermeable molecule that depletes cellular cholesterol content through solubilization of the plasmalemmal cholesterol (Kilsdonk et al, 1995). This cholesterol-binding agent has been efficiently used as a pharmacological tool to study the role of caveolae in vascular reactivity (Dreja et al, 2002;Kaiser et al, 2002;Je et al, 2004). Indeed, in our experiments we observed by electron microscopy that endothelial caveolae were disassembled after exposure of aortic rings to methyl-␤-cyclodextrin.…”

“…Caveolae exist in most cell types and are particularly abundant in endothelial cells and smooth muscle cells (Galbiati et al, 1998;Voldstedlund et al, 2001). The absence of this organelle impairs NO and calcium signaling in the cardiovascular system, causing aberrations in endothelium-dependent relaxation, contractility, and maintenance of myogenic tone (Blair et al, 1999;Darblade et al, 2001;Je et al, 2004).…”

Smooth muscle caveolae differentially regulate specific agonist induced bladder contractions

“…Interestingly, both Cav-1 and Cav-2 are present in arterial smooth muscle, but venous smooth muscle contains only Cav-1 [Segal et al, 1999]. Furthermore, while smooth muscle cells from the ileum, stomach, and uterus express all three caveolins [Taggart et al, 2000], Cav-2 and Cav-3 are not present in aortic smooth muscle [Je et al, 2003] and papillary dilator muscle [Kogo et al, 2006], respectively. In the eye and colon, Cav-3 was detected in the papillary sphincter muscle and inner circular layer, but not in the ciliary muscle or outer longitudinal layer [Kogo et al, 2006].…”