title: Exercise-mediated regulation of Hsp70 expression following aerobic exercise training.
abstract: An issue central to understanding the biological benefits associated with regular exercise training is to elucidate the intracellular mechanisms governing exercise-conferred cardioprotection. Heat shock proteins (HSPs), most notably the inducible 70-kDa HSP family member Hsp70, are believed to participate in the protection of the myocardium during cardiovascular stress. Following acute exercise, activation of PKA mediates the suppression of an intermediary protein kinase, ERK1/2, which phosphorylates and suppresses the activation of the heat shock transcription factor 1 (HSF1). However, following exercise training, ERK1/2 has been reported to regulate the transcriptional activation of several genes involved in cell growth and proliferation and has been shown to be associated with training-mediated myocardial hypertrophy. The present project examined the transcriptional activation of hsp70 gene expression in acutely exercised (60 min at 30 m/min) naïve sedentary and aerobically trained (8 wk, low intensity) male Sprague-Dawley rats. Following acute exercise stress, no significant differences were demonstrated in the expression of myocardial Hsp70 mRNA and activation of PKA between sedentary and trained animals. However, trained animals elicited expression of the hsp70 gene (P < 0.05) in the presence of elevated ERK1/2 activation. Given the association of ERK1/2 and the suppression of hsp70 gene expression following acute exercise in naïve sedentary rats, these results suggest that training results in adaptations that allow for the simultaneous initiation of both proliferative and protective responses. While it is unclear what factors are associated with this training-related shift, increases in HSF1 DNA binding affinity (P < 0.05) and posttranscriptional modifications of the Hsp70 transcript are suggested.
authors.affiliation: School of Kinesiology, Faculty of Health Sciences, The University of Western Ontario, London, Ontario, Canada.
authors.forename: C W James
authors.initials: CW
authors.lastname: Melling
authors.forename: David B
authors.initials: DB
authors.lastname: Thorp
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Milne
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Krause
authors.forename: Earl G
authors.initials: EG
authors.lastname: Noble
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004789:Enzyme Activation; D004837:Epinephrine / Q000097:blood; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D000076249:Heat Shock Transcription Factors; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D005082:Physical Exertion / Q000502:physiology*; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation; D015854:Up-Regulation
chemical_list: D004268:DNA-Binding Proteins; D018840:HSP70 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; C000619709:Hsf1 protein, rat; D012333:RNA, Messenger; D014157:Transcription Factors; D017868:Cyclic AMP-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D004837:Epinephrine