Redox signaling of cardiac HSF1 DNA binding
Copyright policy )Redox signaling of cardiac HSF1 DNA binding
Experiments involving chemical induction of the heat shock response in simple biological systems have generated the hypothesis that protein denaturation and consequential binding of heat shock transcription factor 1 (HSF1) to proximal heat shock elements (HSEs) on heat shock protein ( hsp) genes are the result of oxidation and/or depletion of intracellular thiols. The purpose of the present investigation was to determine the role of redox signaling of HSF1 in the intact animal in response to physiological and pharmacological perturbations. Heat shock and exercise induced HSF1-HSE DNA binding in the rat myocardium ( P < 0.001) in the absence of changes in reduced glutathione (GSH), the major nonprotein thiol in the cell. Ischemia-reperfusion, which decreased GSH content ( P < 0.05), resulted in nonsignificant HSF1-HSE formation. This dissociation between physiological induction of HSF1 and changes in GSH was not gender dependent. Pharmacological ablation of GSH withl-buthionine-[ S, R]-sulfoximine (BSO) treatment increased myocardial HSF1-HSE DNA binding in estrogen-naive animals ( P = 0.007). Thus, although physiological induction of HSF1-HSE DNA binding is likely regulated by mediators of protein denaturation other than cellular redox status, the proposed signaling pathway may predominate with pharmacological oxidation and may represent a plausible and accessible strategy in the development of HSP-based therapies.
- Lawson Research Institute Canada
- University of Michigan–Ann Arbor United States
- Western University Canada
- Oregon Health & Science University United States
- University of Toronto Canada
Male, Hot Temperature, Myocardium, Ovariectomy, Shock, DNA, Motor Activity, Response Elements, Glutathione, Rats, DNA-Binding Proteins, Heat Shock Transcription Factors, Cause of Death, Animals, Female, Buthionine Sulfoximine, Oxidation-Reduction, Heat-Shock Proteins, Signal Transduction, Transcription Factors
Male, Hot Temperature, Myocardium, Ovariectomy, Shock, DNA, Motor Activity, Response Elements, Glutathione, Rats, DNA-Binding Proteins, Heat Shock Transcription Factors, Cause of Death, Animals, Female, Buthionine Sulfoximine, Oxidation-Reduction, Heat-Shock Proteins, Signal Transduction, Transcription Factors
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