title: Superoxide radicals have a protective role during H2O2 stress.
abstract: Reactive oxygen species (ROS) consist of potentially toxic, partly reduced oxygen species and free radicals. After H(2)O(2) treatment, yeast cells significantly increase superoxide radical production. Respiratory chain complex III and possibly cytochrome b function are essential for this increase. Disruption of complex III renders cells sensitive to H(2)O(2) but not to the superoxide radical generator menadione. Of interest, the same H(2)O(2)-sensitive mutant strains have the lowest superoxide radical levels, and strains with the highest resistance to H(2)O(2) have the highest levels of superoxide radicals. Consistent with this correlation, overexpression of superoxide dismutase increases sensitivity to H(2)O(2), and this phenotype is partially rescued by addition of small concentrations of menadione. Small increases in levels of mitochondrially produced superoxide radicals have a protective effect during H(2)O(2)-induced stress, and in response to H(2)O(2), the wild-type strain increases superoxide radical production to activate this defense mechanism. This provides a direct link between complex III as the main source of ROS and its role in defense against ROS. High levels of the superoxide radical are still toxic. These opposing, concentration-dependent roles of the superoxide radical comprise a form of hormesis and show one ROS having a hormetic effect on the toxicity of another.
authors.affiliation: Ramaciotti Centre for Gene Function Analysis, School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW 2052, Australia Heart Research Institute, Newtown, NSW 2042, Australia Internal Medicine I, Paracelsus Medical University, 5020 Salzburg, Austria Department of Cell Biology, University of Salzburg, 5020 Salzburg, Austria.
authors.forename: Geoffrey W
authors.initials: GW
authors.lastname: Thorpe
authors.forename: Mayfebelle
authors.initials: M
authors.lastname: Reodica
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Davies
authors.forename: Gino
authors.initials: G
authors.lastname: Heeren
authors.forename: Stefanie
authors.initials: S
authors.lastname: Jarolim
authors.forename: Bethany
authors.initials: B
authors.lastname: Pillay
authors.forename: Michael
authors.initials: M
authors.lastname: Breitenbach
authors.forename: Vincent J
authors.initials: VJ
authors.lastname: Higgins
authors.forename: Ian W
authors.initials: IW
authors.lastname: Dawes
mesh_terms: D000222:Adaptation, Physiological / Q000187:drug effects; D045303:Cytochromes b / Q000378:metabolism; D019610:Cytoprotection / Q000187:drug effects*; D004579:Electron Transport / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000633:toxicity*; D050296:Microbial Viability / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D018384:Oxidative Stress / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D013312:Stress, Physiological / Q000187:drug effects*; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D013481:Superoxides / Q000494:pharmacology*
chemical_list: D012333:RNA, Messenger; D013481:Superoxides; D045303:Cytochromes b; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase