FASEB journal : official publication of the Federation of American Societies for Experimental Biology
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Caveolae, small invaginations in the plasma membrane, contain caveolins (Cav) that scaffold signaling molecules including the tyrosine kinase Src. We tested the hypothesis that cardiac protection involves a caveolin-dependent mechanism. We used in vitro and in vivo models of ischemia-reperfusion injury, electron microscopy (EM), transgenic mice, and biochemical assays to address this hypothesis. ⋯ Cav-1(-/-) mice exposed to isoflurane showed significant alterations in Src phosphorylation and recruitment of C-terminal Src kinase, a negative regulator of Src, when compared to WT mice. The results indicate that isoflurane modifies cardiac myocyte sarcolemmal membrane structure and composition and that activation of Src and phosphorylation of Cav-1 contribute to cardiac protection. Accordingly, therapies targeted to post-translational modification of Src and Cav-1 may provide a novel approach for such protection.