Caveolin-1 regulates contractility in differentiated vascular smooth muscle.
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 PKC-dependent 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 alpha agonist. Peptide loading also resulted in a significant inhibition of phorbol ester-induced adducin Ser662 phosphorylation, an intracellular monitor of PKC kinase activity, ERK1/2 activation, and Ser789 phosphorylation of the actin binding protein caldesmon. alpha-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 alpha-agonist were obtained with the cholesterol-depleting agent methyl-beta-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.
Je
Hyun-Dong
HD
Boston Biomedical Research Institute, 64 Grove St. Watertown, MA 02472, USA.
Gallant
Cynthia
C
Leavis
Paul C
PC
Morgan
Kathleen G
KG
D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology; D001011:Aorta / Q000378:metabolism; D002148:Calmodulin-Binding Proteins / Q000378:metabolism / Q000494:pharmacology; D051242:Caveolin 1; D022461:Caveolins / Q000494:pharmacology / Q000502:physiology*; D005289:Ferrets; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D010446:Peptide Fragments / Q000494:pharmacology; D010703:Phorbol Esters / Q000494:pharmacology; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
D000924:Anticholesteremic Agents; D002148:Calmodulin-Binding Proteins; D051242:Caveolin 1; D022461:Caveolins; D010446:Peptide Fragments; D010703:Phorbol Esters; C047907:12-deoxyphorbol-13-isobutyrate-20-acetate; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases