title: Inhibition of the oxidative stress response by heat stress in Caenorhabditis elegans.
abstract: It has long been recognized that simultaneous exposure to heat stress and oxidative stress shows a synergistic interaction that reduces organismal fitness, but relatively little is known about the mechanisms underlying this interaction. We investigated the role of molecular stress responses in driving this synergistic interaction using the nematode Caenorhabditis elegans To induce oxidative stress, we used the pro-oxidant compounds acrylamide, paraquat and juglone. As expected, we found that heat stress and oxidative stress interact synergistically to reduce survival. Compared with exposure to each stressor alone, during simultaneous sublethal exposure to heat stress and oxidative stress the normal induction of key oxidative-stress response (OxSR) genes was generally inhibited, whereas the induction of key heat-shock response (HSR) genes was not. Genetically activating the SKN-1-dependent OxSR increased a marker for protein aggregation and decreased whole-worm survival during heat stress alone, with the latter being independent of HSF-1. In contrast, compared with wild-type worms, inactivating the HSR by HSF-1 knockdown, which would be expected to decrease basal heat shock protein expression, increased survival during oxidative stress alone. Taken together, these data suggest that, in C. elegans, the HSR and OxSR cannot be simultaneously activated to the same extent that each can be activated during a single stressor exposure. We conclude that the observed synergistic reduction in survival during combined exposure to heat stress and oxidative stress is due, at least in part, to inhibition of the OxSR during activation of the HSR.
authors.affiliation: Department of Biology, University of Florida, Gainesville, FL 32611, USA.
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Crombie
authors.affiliation: Department of Biology, University of Florida, Gainesville, FL 32611, USA.
authors.forename: Lanlan
authors.initials: L
authors.lastname: Tang
authors.affiliation: Department of Biology, University of Florida, Gainesville, FL 32611, USA.
authors.forename: Keith P
authors.initials: KP
authors.lastname: Choe
authors.affiliation: Department of Biology, University of Florida, Gainesville, FL 32611, USA djulian@ufl.edu.
authors.forename: David
authors.identifier: 0000-0003-1143-2813
authors.initials: D
authors.lastname: Julian
mesh_terms: D000222:Adaptation, Physiological / Q000187:drug effects / Q000235:genetics; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D017173:Caenorhabditis elegans / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004777:Environment; D005786:Gene Expression Regulation / Q000187:drug effects; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000378:metabolism; D018869:Heat-Shock Response / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D016877:Oxidants / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics; D066329:Protein Aggregates / Q000187:drug effects; D034622:RNA Interference / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D016019:Survival Analysis; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D015415:Biomarkers; D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; D016877:Oxidants; D066329:Protein Aggregates; D014157:Transcription Factors; D049452:Green Fluorescent Proteins; C073702:skn-1 protein, C elegans
keywords: HSF-1; Multiple stressors; SKN-1; Survival; Synergistic interaction