Epidemiological studies have demonstrated that chronic exercise is cardioprotective, and recent evidence from our laboratory suggests a key role for protein kinase C (PKC)-dependent pathways, at least in part, as a cellular basis for this response. However, the dose-response relationship linking exercise volume and the time course of isoform-specific PKC activation are poorly understood. Aim: The purpose of this investigation was to determine the effects of acute exercise of varying durations on PKC subcellular distribution and phosphorylation in the rat left ventricle. Methods: Adult (5 months) male Fischer-344 more rats were subjected to a single bout (OB) or 7 days (SB) of treadmill running (n = 6/group; 23 m min-1, 20 min), and compared with sedentary controls (SED; n = 8). Hearts were isolated immediately after [early window (EW); n = 3/group] or 24 h after the last exercise bout [late window (LW); n = 3/group] in OB and SD, respectively. Total PKC and subcellular distribution for the α, δ, ε, βI, and βII isoforms, as well as phosphorylated (phospho-) PKCε (pSer729), PKCα (pSer657) and PKCδ (pThr)07) levels were assessed by western blotting. Protein kinase Cε and PKCα mRNA levels were assessed by real time polymerase chain reaction. Results: Following OB, PKCβI protein levels were reduced, while total phospho-PKCε (pSer729), PKCα (pSer657) and PKCδ (pThr507) levels were increased during EW (P < 0.05). Interestingly, total PKCδ (31%) and membrane-associated PKCα (24%) levels decreased from EW to LW (P < 0.05). In contrast, SB yielded chronic increases in total PKCε (80.5%) levels and PKCδ (20.0%) levels (P < 0.03), with reversal of effects on phospho-PKCε (Ser729), phospho-PKCα (Ser657) and phospho-PKCδ (Thr507) levels observed with OB. Reductions in total phospho-PKCα (Ser657) persisted at SB (26.1%; P < 0.02). Interestingly, mRNA levels for PKCε were significantly increased following SB while PKCα mRNA levels were reduced, respectively. Conclusion: These data suggest that divergent patterns of PKC activation occur following OB and SB at both the transcriptional and translational levels. That similar patterns of PKC translocation are observed in experimental models of ischaemic preconditioning and genetic PKC manipulation provide evidence for a dose-dependent cardioprotective phenotype induced by physical activity.
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