Oxidative Stress Impairs the Heat Stress Response and Delays Unfolded Protein Recovery 27/11/2009 05:29:31
Abstract
Background: Environmental changes, air pollution and ozone depletion are increasing oxidative stress, and global warming
threatens health by heat stress. We now face a high risk of simultaneous exposure to heat and oxidative stress. However,
there have been few studies investigating their combined adverse effects on cell viability.
Principal Findings: Pretreatment of hydrogen peroxide (H2O2) specifically and highly sensitized cells to heat stress, and
enhanced loss of mitochondrial membrane potential. H2O2 exposure impaired the HSP40/HSP70 induction as heat shock
response (HSR) and the unfolded protein recovery, and enhanced eIF2a phosphorylation and/or XBP1 splicing, land marks
of ER stress. These H2O2-mediated effects mimicked enhanced heat sensitivity in HSF1 knockdown or knockout cells.
Importantly, thermal preconditioning blocked H2O2–mediated inhibitory effects on refolding activity and rescued HSF1 +/+
MEFs, but neither blocked the effects nor rescued HSF1 -/- MEFs. These data strongly suggest that inhibition of HSR and
refolding activity is crucial for H2O2–mediated enhanced heat sensitivity.
Conclusions: H2O2 blocks HSR and refolding activity under heat stress, thereby leading to insufficient quality control and
enhancing ER stress. These uncontrolled stress responses may enhance cell death. Our data thus highlight oxidative stress
as a crucial factor affecting heat tolerance.
Citation: Adachi M, Liu Y, Fujii K, Calderwood SK, Nakai A, et al. (2009) Oxidative Stress Impairs the Heat Stress Response and Delays Unfolded Protein Recovery. PLoS ONE 4(11): e7719. doi:10.1371/journal.pone.0007719
Editor: Michael Polymenis, Texas A&M University, United States of America
Received August 3, 2009; Accepted October 5, 2009; Published November 11, 2009
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