Regulation of protein kinase C-epsilon and its age-dependence.

Protein kinase C is an important mediator in the cardioprotection of ischemic preconditioning and has been shown to translocate to mitochondria upon activation. However, little is known about the cellular signaling underlying the translocation of isoforms to mitochondria and its age-dependence. The present study aimed to explore whether adenosine-induced translocation of to mitochondria is mediated by caveolin-3 and/or adenosine A2B receptor/PI3 kinase mediated signaling, and whether the mitochondrial targeting of duanyu1531ε is age-related. Immunofluorescence imaging of isolated mitochondria from cardiomyocytes and H9c2 cells showed that while adenosine-induced increase in mitochondrial duanyu1531ε was inhibited by adenosine A1 receptor blocker, pretreatment with adenosine A2B receptor specific inhibitor MRS 1754 or PI3K inhibitor Wortmannin did not significantly reduce adenosine-mediated increase in mitochondrial Interestingly, adenosine-induced increase in mitochondrial translocation of duanyu1531ε was significantly blocked by suppressing caveolin-3 expression with specific siRNA. When compared to that in young adult rat hearts, the level of mitochondrial duanyu1531ε in middle-aged rat hearts was significantly lower at the basal condition and in response to adenosine treatment, along with largely decreased mitochondrial HSP90 and TOM70 protein expression. We demonstrate that adenosine-induced translocation of duanyu1531ε to mitochondria is mediated by a caveolin-3-dependent mechanism and this process is age-related, possibly in part, through regulation of HSP90 and TOM70 expression. These results point out a novel mechanism in regulating duanyu1531 function in mitochondria.

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