Role of caveolin‐3 in adenosine‐induced increase in mitochondrial PKCε

Abstract

Activation of adenosine receptors has been shown to promote translocation of PKC isoforms to both caveolar plasma membrane and mitochondria. Adenosine receptors, PKC and caveolin‐3 play important roles in the cardioprotection of ischemic preconditioning. The present study was designed to determine whether adenosine receptor activation‐induced translocation of PKCε to mitochondria is caveolin‐3‐dependent. Immunofluorescence imaging of isolated mitochondria showed that adenosine‐induced increase in mitochondria PKCε was inhibited by adenosine A1 receptor specific inhibitor DPCPX (36.0 ± 1.2% vs. 72.7 ± 1.8% in cardiomyocytes and 19.0 ± 1.0% vs 57.5 ± 2.0% in H9c2 cells, n=3, P<0.01). Neither adenosine A2B receptor specific inhibitor MRS1754 nor PI3K kinase inhibitor Wortmannin prevented adenosine‐induced increase in mitochondrial PKCε. Interestingly, adenosine‐induced mitochondrial translocation of PKCε was significantly reduced by suppressing caveolin‐3 expression with specific siRNA (52.0 ± 2.0% vs. 17.7 ± 2.0%, adenosine vs. adenosine/caveolin‐3‐siRNA in H9c2 cells, n=3, P<0.01), while negative siRNA had no effect. In conclusion, we demonstrate that adenosine receptor activation induces caveolin‐3‐dependent translocation of PKCε to mitochondria. These results point out a novel mechanism in regulating PKC isoform in mitochondria.