Ablation of the heat shock factor-1 increases susceptibility to hyperoxia-mediated cellular injury

Vivek Malhotra, Neil W. Kooy, Alvin G. Denenberg, Katherine E. Dunsmore, Hector R. Wong

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

High concentrations of oxygen (hyperoxia) are known to cause cellular injury and death. The heat shock response is a highly conserved cellular defense mechanism that protects cells against various environmental stressors, including hyperoxia. Herein we determined the role of heat shock factor-1 (HSF-1), a major component of the heat shock response, in protecting cells against hyperoxia. Embryonic fibroblasts from HSF-1-null mutant mice (HSF-1 -/-cells) were compared to wild-type embryonic fibroblasts (HSF-1 +/+ cells) following 24 hours' exposure to room air or hyperoxia (95% O2). Acute survival in hyperoxia was decreased in HSF-1 -/- cells as compared to HSF-1 +/+ cells. Intracellular ATP levels were significantly lower in the HSF-1 -/- cells as compared to the HSF-1 +/+ cells exposed to hyperoxia. Isoprostane levels, a marker of membrane lipid peroxidation, were significantly higher in the HSF-1 -/- cells as compared to the HSF-1 +/+ cells exposed to hyperoxia. Restoration of HSF-1 in the HSF-1 -/- cells by stable transfection with a HSF-1 expression plasmid improved survival in hyperoxia when compared to HSF-1 -/- cells stably transfected with the empty expression vector. Hyperoxia increased activation of HSF-1 in HSF-1 +/+ cells and in HSF-1 -/- cells stably, transfected with the HSF-1 expression plasmid. These data demonstrate that HSF-1 plays an important role in conferring resistance to hyperoxia in vitro.

Original languageEnglish (US)
Pages (from-to)609-622
Number of pages14
JournalExperimental Lung Research
Volume28
Issue number8
DOIs
StatePublished - Dec 2002

Bibliographical note

Copyright:
Copyright 2005 Elsevier B.V., All rights reserved.

Keywords

  • HSF-1
  • Heat shock
  • Hyperoxia

Fingerprint

Dive into the research topics of 'Ablation of the heat shock factor-1 increases susceptibility to hyperoxia-mediated cellular injury'. Together they form a unique fingerprint.

Cite this