Extracellular heat shock protein 60, cardiac myocytes, and apoptosis

Se Chan Kim, James P. Stice, Le Chen, James S. Jung, Sanjiv Gupta, Yin Wang, Georg Baumgarten, Joann Trial, Anne A Knowlton

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Abstract

RATIONALE: Previously, we have found that changes in the location of intracellular heat shock protein (HSP)60 are associated with apoptosis. HSP60 has been reported to be a ligand of Toll-like receptor (TLR)-4. OBJECTIVE: We hypothesized that extracellular HSP60 (exHSP60) would mediate apoptosis via TLR4. METHODS AND RESULTS: Adult rat cardiac myocytes were treated with HSP60, either recombinant human or with HSP60 purified from the media of injured rat cardiac myocytes. ExHSP60 induced apoptosis in cardiac myocytes, as detected by increased caspase 3 activity and increased DNA fragmentation. Apoptosis could be reduced by blocking antibodies to TLR4 and by nuclear factor κB binding decoys, but not completely inhibited, even though similar treatment blocked lipopolysaccharide-induced apoptosis. Three distinct controls showed no evidence for involvement of a ligand other than exHSP60 in the mediation of apoptosis. CONCLUSIONS: This is the first report of HSP60-induced apoptosis via the TLRs. HSP60-mediated activation of TLR4 may be a mechanism of myocyte loss in heart failure, where HSP60 has been detected in the plasma.

Original languageEnglish (US)
Pages (from-to)1186-1195
Number of pages10
JournalCirculation Research
Volume105
Issue number12
DOIs
StatePublished - Dec 2009

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Keywords

  • Apoptosis
  • Cardiac myocytes
  • Heat shock protein 60
  • Inflammation
  • TLR4
  • Toll-like receptor-4
  • Tumor necrosis factor

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Kim, S. C., Stice, J. P., Chen, L., Jung, J. S., Gupta, S., Wang, Y., Baumgarten, G., Trial, J., & Knowlton, A. A. (2009). Extracellular heat shock protein 60, cardiac myocytes, and apoptosis. Circulation Research, 105(12), 1186-1195. https://doi.org/10.1161/CIRCRESAHA.109.209643