Oxidative Stress Impairs the Heat Stress Response and Delays Unfolded Protein Recovery
Open Access
- 11 November 2009
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 4 (11), e7719
- https://doi.org/10.1371/journal.pone.0007719
Abstract
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. 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 eIF2α 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. 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.This publication has 27 references indexed in Scilit:
- Induction of heat shock proteins for protection against oxidative stressAdvanced Drug Delivery Reviews, 2009
- Preventing oxidative stress: a new role for XBP1Cell Death & Differentiation, 2009
- Multiple Mechanisms Contribute to Inhibit Transcription in Response to DNA DamageOnline Journal of Public Health Informatics, 2008
- Heat Illness and Heat StrokePediatrics in Review, 2007
- HeatstrokeSeminars in Neurology, 2005
- Bmf is a possible mediator in histone deacetylase inhibitors FK228 and CBHA-induced apoptosisCell Death & Differentiation, 2005
- Impaired IgG Production in Mice Deficient for Heat Shock Transcription Factor 1Online Journal of Public Health Informatics, 2004
- Nrf2 Is a Direct PERK Substrate and Effector of PERK-Dependent Cell SurvivalMolecular and Cellular Biology, 2003
- Targeted disruption of hsf1 leads to lack of thermotolerance and defines tissue‐specific regulation for stress‐inducible Hsp molecular chaperonesJournal of Cellular Biochemistry, 2002
- XBP1 mRNA Is Induced by ATF6 and Spliced by IRE1 in Response to ER Stress to Produce a Highly Active Transcription FactorCell, 2001