The heat shock paradox and cardiac myocytes: Role of heat shock factor

Samuel Kobba, Se Chan Kim, Le Chen, Eunjung Kim, Alice L. Tran, Pascal Knuefermann, Anne A Knowlton

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)478-484
Number of pages7
JournalShock
Volume35
Issue number5
DOIs
StatePublished - May 2011

Keywords

  • apoptosis
  • HSF-1
  • HSP60
  • iNOS
  • MODS
  • NF-κB

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine
  • Emergency Medicine

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