Cytosolic heat shock protein 60, hypoxia, and apoptosis

S. Gupta, Anne A Knowlton

Research output: Contribution to journalArticlepeer-review

134 Scopus citations

Abstract

Background - Heat shock protein (HSP)60 is an abundant protein found primarily in the mitochondria, though 15% to 20% is found in the cytosol. Previously we observed that HSP60 complexes with bax in the cytosol. Reduction in HSP60 precipitates translocation of bax to the mitochondria and apoptosis. We hypothesized that HSP60 would decrease with hypoxia/reoxygenation and that this would precipitate bax translocation to the mitochondria and release of cytochrome c. Methods and Results - Adult rat cardiac myocytes were studied at end-hypoxia and at 10 and 24 hours of reoxygenation. HSP60 levels were unchanged at end-hypoxia and decreased 33% and 40% at 10 and 24 hours of reoxygenation, whereas HSP72 increased 80% and 110%. Bax and bcl-2 decreased during reoxygenation. However, cytochrome c release occurred at end-hypoxia, before reoxygenation. Cell fractionation was done to analyze this further. In normal myocytes, bax and HSP60 were present in the cytosol, and bax coimmunoprecipitated with cytosolic HSP60. At end-hypoxia, mitochondrial HSP60 was unchanged, but cytosolic HSP60 had disappeared and was now in the plasma membrane fraction. Concurrently, bax was no longer in the cytosol but now in the mitochondria. Thus, although total HSP60 remained the same, it no longer complexed with bax, and bax was free to translocate to the mitochondria and precipitate apoptosis. Reduction in ATP had a similar effect. Conclusions - These studies show that hypoxia results in disassociation of the HSP60-bax complex with translocation of cytosolic HSP60 to the plasma membrane and bax to the mitochondria. This is sufficient to trigger apoptosis.

Original languageEnglish (US)
Pages (from-to)2727-2733
Number of pages7
JournalCirculation
Volume106
Issue number21
DOIs
StatePublished - Nov 19 2002

Keywords

  • Apoptosis
  • Hypoxia
  • Ischemia
  • Myocytes

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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