title: The heat shock paradox and cardiac myocytes: role of heat shock factor.
abstract: The induction of the heat shock (HS) response is accepted to be a protective response, reducing injury and improving cell survival. However, when inflammation precedes HS, there is an unexpected increase in injury, known as the HS paradox, which is hypothesized to be a mechanism underlying multiorgan dysfunction. We hypothesized that the HS paradox would occur in adult cardiac myocytes and that HS factor (HSF) 1 would contribute to injury. Heat shock at 42°C and TNF (10 ng/mL) were used as the HS and the inflammatory insult, respectively. The combination of TNF followed by HS (TNF/HS) caused the greatest amount of apoptosis in adult rat cardiac myocytes. TNF/HS resulted in an increase in HS protein (HSP) 60, compared with untreated cells, those receiving HS/TNF, or TNF alone. There was no increase in heme oxygenase 1 in any of the groups. Heat shock protein 72 increased in all the groups, with the greatest levels with TNF/HS. Nuclear factor κB activation was greatest with TNF/HS. Pretreatment with a DNA-binding decoy for HSF-1 prevented the increase in HSPs and decreased apoptosis in all groups. However, the increase in iNOS, seen in all treatment groups, was unaffected by the HSF-1-binding decoy. We conclude that the HS paradox occurs in adult cardiac myocytes, that HSP60 is increased as part of the HS paradox, and that HSF-1 activation contributes to injury.
authors.affiliation: Molecular & Cellular Cardiology, Cardiovascular Division, University of California, Davis, California, USA.
authors.forename: Samuel
authors.initials: S
authors.lastname: Kobba
authors.forename: Se-Chan
authors.initials: SC
authors.lastname: Kim
authors.forename: Le
authors.initials: L
authors.lastname: Chen
authors.forename: Eunjung
authors.initials: E
authors.lastname: Kim
authors.forename: Alice L
authors.initials: AL
authors.lastname: Tran
authors.forename: Pascal
authors.initials: P
authors.lastname: Knuefermann
authors.forename: Anne A
authors.initials: AA
authors.lastname: Knowlton
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D015153:Blotting, Western; D002470:Cell Survival / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D018834:Chaperonin 60 / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D000076249:Heat Shock Transcription Factors; D018869:Heat-Shock Response / Q000235:genetics / Q000502:physiology; D007770:L-Lactate Dehydrogenase / Q000235:genetics / Q000378:metabolism; D008297:Male; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D018834:Chaperonin 60; D004268:DNA-Binding Proteins; D000076249:Heat Shock Transcription Factors; D016328:NF-kappa B; D014157:Transcription Factors; D007770:L-Lactate Dehydrogenase; D052247:Nitric Oxide Synthase Type II