Decline in caveolin-1 expression and scaffolding of G protein receptor kinase-2 with age in Fischer 344 aortic vascular smooth muscle.
Beta-adrenergic receptor (beta-AR)-mediated vasorelaxation declines with age in humans and animal models. This is not caused by changes in expression of beta-AR, G alpha s, adenylyl cyclase, or protein kinase A but is associated with decreased cAMP production. Expression and activity of G protein receptor kinase-2 ( GRK-2), which phosphorylates and desensitizes the beta-AR, increases with age in rat aortic tissue. Caveolin scaffolds the beta-AR, GRK, and other proteins within "signaling pockets" and inhibits GRK activity when bound. We questioned the effect of age on caveolin-1 expression and interaction between caveolin-1 and GRK-2 in vascular smooth muscle (VSM) isolated from 2-, 6-, 12-, and 24-mo-old male Fischer 344 rat aorta. Western blot analysis found expression of caveolin-1 declined with age (6-, 12- and 24-mo-old rat aortas express 92, 50, and 42% of 2-mo-old rat aortas, respectively). Results from density-buoyancy analysis showed a lower percentage of GRK in caveolin-1-specific fractions with age (6-, 12- and 24-mo-old rat aortas express 95, 56, and 12% of 2-mo-old rat aortas, respectively). Coimmunoprecipitation confirmed this finding; density of GRK in caveolin-1 immunoprecipitates was 97, 30, and 21% of 2-mo-old aortas compared with 6-, 12- and 24-mo-old animals, respectively. Immunohistocytochemistry and confocal microscopy confirmed that GRK-2 and caveolin-1 colocalize in VSM. These results suggest that in nonoverexpressed, intact tissue, the decline in beta-AR-mediated vasorelaxation may be caused by both a reduction in caveolin-1 expression and a reduction in binding of GRK-2 by caveolin-1. This could lead to an increase in the fraction of free GRK-2, which could phosphorylate and desensitize the beta-AR.[1]References
- Decline in caveolin-1 expression and scaffolding of G protein receptor kinase-2 with age in Fischer 344 aortic vascular smooth muscle. Schutzer, W.E., Reed, J.F., Mader, S.L. Am. J. Physiol. Heart Circ. Physiol. (2005) [Pubmed]
Annotations and hyperlinks in this abstract are from individual authors of WikiGenes or automatically generated by the WikiGenes Data Mining Engine. The abstract is from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.About WikiGenesOpen Access LicencePrivacy PolicyTerms of Useapsburg