Regulation of myocardial heat shock protein 70 gene expression following exercise.
Post-exercise induction of myocardial heat shock protein (Hsp70) gene expression involves the activation of the heat shock transcription factor (HSF1). While the exact mechanisms governing the regulation of HSF1 are unclear, activation is believed to occur subsequent to hyperphosphorylation of specific serine residues. As two important serine kinases, protein kinase A (PKA) and protein kinase C (PKC), have been implicated in many phosphorylative events in myocardial cells, we examined the role of these kinases in the activation of Hsp70 gene expression following exercise. In this report, we show that prior administration of a PKA inhibitor, N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide ?2HCl (H-89; 0.36 mg/kg), significantly suppressed the elevation in Hsp70 mRNA (P < 0.05) and protein synthesis (P < 0.05) in male Sprague-Dawley rats following a single bout of exercise. In contrast, this post-exercise elevation in Hsp70 mRNA and protein synthesis was not suppressed following the administration of a PKC inhibitor chelerythrine chloride (CHEL; 5 mg/kg) (P < 0.05). Of note, inhibition of PKA did not alter the nuclear localization and binding affinity of HSF1 to the promotor region of the Hsp70 gene. These data indicate that PKA, and not PKC, plays a necessary role in the early exercise-induced regulation of Hsp70 gene expression, downstream of DNA-binding acquisition. However, the current study does not support previous observations regarding major changes in HSF1 phosphorylation and suggests that other PKA-related mechanisms mediate the activation of Hsp70 gene expression following exercise.
Melling
C W James
CW
The University of Western Ontario, Faculty of Health Sciences, School of Kinesiology, London, Ontario, Canada N6A 3K7.
Thorp
David B
DB
Noble
Earl G
EG
D000818:Animals; D001831:Body Temperature; D002467:Cell Nucleus / Q000737:chemistry; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D003593:Cytoplasm / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000032:analysis / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D005786:Gene Expression Regulation; D006003:Glycogen / Q000032:analysis / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D000076249:Heat Shock Transcription Factors; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism*; D010805:Physical Conditioning, Animal; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000494:pharmacology; D014157:Transcription Factors
D004268:DNA-Binding Proteins; D018840:HSP70 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; C000619709:Hsf1 protein, rat; D007546:Isoquinolines; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; D014157:Transcription Factors; D006003:Glycogen; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide