Myocardial Hsp70 phosphorylation and PKC-mediated cardioprotection following exercise.
Both protein kinase C (PKC) activation and Hsp70 expression have been shown to be key components for exercise-mediated myocardial protection during ischemia-reperfusion injury. Given that Hsp70 has been shown to undergo inducible phosphorylation in striated muscle and liver, we hypothesized that PKC may regulate myocardial Hsp70 function and subsequent exercise-conferred cardioprotection through this phosphorylation. Hence, acute exercise of male Sprague-Dawley rats (30 m/min for 60 min at 2% grade) was employed to assess the role of PKC and its selected isoforms in phosphorylation of Hsp70 and protection of the myocardium during ischemia-reperfusion injury. It was observed that administration of the PKC inhibitor chelerythrine chloride (5 mg/kg) suppressed the activation of three exercise-induced PKC isoforms (PKCalpha, PKCdelta, and PKCepsilon) and attenuated the exercise-mediated reduction of myocardial infarct size during ischemia-reperfusion injury. While this study also demonstrated that exercise led to an alteration in the phosphorylation status of Hsp70, this posttranslational modification appeared to be dissociated from PKC activation, as exercise-induced phosphorylation of Hsp70 was unchanged following inhibition of PKC. Taken together, these results indicate that selected isoforms of PKC play an important role in exercise-mediated protection of the myocardium during ischemia-reperfusion injury. However, exercise-induced phosphorylation of Hsp70 does not appear to be a mechanism by which PKC induces this cardioprotective effect.
Melling
C W James
CW
School of Kinesiology, Faculty of Health Sciences, The University of Western Ontario, London, Ontario, Canada.
Thorp
David B
DB
Milne
Kevin J
KJ
Noble
Earl G
EG
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002316:Cardiotonic Agents / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D009203:Myocardial Infarction / Q000201:enzymology / Q000473:pathology; D009206:Myocardium / Q000201:enzymology*; D010766:Phosphorylation / Q000187:drug effects; D010805:Physical Conditioning, Animal; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D002316:Cardiotonic Agents; D018840:HSP70 Heat-Shock Proteins; D007527:Isoenzymes; D047428:Protein Kinase Inhibitors; D011493:Protein Kinase C