Medical College of Wisconsin
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Heat shock factor 1-mediated thermotolerance prevents cell death and results in G2/M cell cycle arrest. Cell Stress Chaperones 2001 Oct;6(4):326-36

Date

01/25/2002

Pubmed ID

11795469

Pubmed Central ID

PMC434415

DOI

10.1379/1466-1268(2001)006<0326:hsfmtp>2.0.co;2

Scopus ID

2-s2.0-0035204193 (requires institutional sign-in at Scopus site)   49 Citations

Abstract

Mammalian cells respond to environmental stress by activating heat shock transcription factors (eg, Hsf1) that regulate increased synthesis of heat shock proteins (Hsps). Hsps prevent the disruption of normal cellular mitosis, meiosis, or differentiation by environmental stressors. To further characterize this stress response, transformed wild-type Hsf1+/+ and mutant Hsf1-/- mouse embryonic fibroblasts (MEFs) were exposed to (1) lethal heat (45 degrees C, 60 minutes), (2) conditioning heat (43 degrees C, 30 minutes), or (3) conditioning followed by lethal heat. Western blot analysis demonstrated that only Hsf1+/+ MEFs expressed inducible Hsp70s and Hsp25 following conditioning or conditioning and lethal heat. Exposure of either Hsf1+/+ or Hsf1-/- MEFs to lethal heat resulted in cell death. However, if conditioning heat was applied 6 hours before lethal heat, more than 85% of Hsf1+/+ MEFs survived, and cells in G2/M transiently increased 3-fold. In contrast, conditioned Hsf1-/- MEFs neither survived lethal heat nor exhibited this G2/M accumulation. Coinfection with adenoviral Hsp70 and Hsp25 constructs did not fully recreate thermotolerance in either Hsf1+/+ or Hsf1-/- MEFs, indicating other Hsf1-mediated gene expression is required for complete thermotolerance. These results demonstrate the necessity of Hsf1-mediated gene expression for thermotolerance and the involvement of cell cycle regulation, particularly the G2/M transition, in this thermotolerant response.

Author List

Luft JC, Benjamin IJ, Mestril R, Dix DJ

Author

Ivor J. Benjamin MD Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Cell Death
Cell Line, Transformed
Cell Survival
DNA-Binding Proteins
G2 Phase
Heat Shock Transcription Factors
Heat-Shock Proteins
Heat-Shock Response
Hot Temperature
Humans
Mice
Mitosis
Mutation
Time Factors
Transcription Factors