Enhanced expression of heat shock proteins in gradually dying cells and their release from necrotically dead cells

Exp Cell Res. 2005 Oct 15;310(1):229-36. doi: 10.1016/j.yexcr.2005.07.014.


Heat shock proteins (HSPs) have molecular chaperone functions in protein biogenesis as well as cytoprotective functions against deleterious environmental stresses, and they work mainly inside of the cells. HSPs are usually induced in living cells that have been exposed to mild stresses or have recovered from severe stresses. Here, we show the enhanced synthesis of HSPs in gradually and necrotically dying cells that were treated with a high concentration of acrylamide (10 mM). This treatment caused irreversible cell death. The synthesis of HSPs, which was enhanced before cell death, was mediated by the activation of heat shock transcription factor 1 (HSF1); that is, the treatment led to the phosphorylation of HSF1, formation of characteristic HSF1 granules in the nucleus, and acquisition of DNA binding ability of HSF1. The induction of HSPs by acrylamide treatment was dependent on the consensus sequence of heat shock element (HSE) as demonstrated by a reporter assay. Also, several HSPs (Hsp90, Hsc70, Hsp70, Hsp60, Hsp47, Hsp40, and Hsp27) were detected outside of the cells after the treatment with acrylamide, indicating that these HSPs are released from necrotically dead cells. These results suggest that when cells are slowly and irreversibly dying, they augment the expression of HSPs and release them outside of the cells as a danger signal or dying messages.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acrylamide / pharmacology*
  • Apoptosis / drug effects*
  • Cell Line
  • DNA-Binding Proteins / metabolism
  • Gene Expression Regulation / drug effects
  • HeLa Cells
  • Heat Shock Transcription Factors
  • Heat-Shock Proteins / genetics
  • Heat-Shock Proteins / metabolism*
  • Humans
  • Necrosis*
  • Time Factors
  • Transcription Factors / metabolism
  • Up-Regulation / drug effects


  • DNA-Binding Proteins
  • HSF1 protein, human
  • Heat Shock Transcription Factors
  • Heat-Shock Proteins
  • Transcription Factors
  • Acrylamide