Antioxidant small molecules confer variable protection against oxidative damage in yeast mutants

J Agric Food Chem. 2008 Dec 24;56(24):11740-51. doi: 10.1021/jf802829r.


To assess the capacity of small molecules to function as antioxidants in pathologic conditions, a set of yeast assays utilizing strains deficient in the antioxidant machinery was applied with measurements of reactive oxygen species (ROS), glutathione (GSH/GSSG), and induction of the stress responsive proteins oye2 and oye3. Yeast strains deficient in superoxide dismutase (Delta sod1), catalase A (Delta cta1), and double-deficient in Old Yellow enzyme 2 and glutathione reductase 1 (Delta oye2 glr1) were supplemented with ascorbic acid, beta-carotene, caffeic acid, or quercetin, subjected to pro-oxidant insult, and monitored for growth recovery. Ascorbic acid and caffeic acid protected cells under most circumstances, whereas beta-carotene and quercetin protection was highly context dependent, exhibiting protection in some cases and inhibition in others. Beta-carotene and quercetin elevated substantially endogenous levels of ROS in some yeast mutants. Quercetin supplementation increased significantly GSH and GSSG levels but could not maintain GSH levels in H(2)O(2)-exposed cells. Induction of the stress response machinery was manifested by the strong up-regulation of a chromosomally encoded OYE2-GFP fusion. In the case of quercetin, there was simultaneous induction of OYE3-GFP, which was previously shown to sensitize cells to H(2)O(2)-induced programmed cell death (PCD). Taken together, the results show that mutations in the antioxidant machinery affect significantly the capacity of dietary antioxidants to protect cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antioxidants / pharmacology*
  • Catalase / genetics
  • Catalase / metabolism
  • Glutathione / metabolism
  • Microbial Viability / drug effects
  • Mutation*
  • Oxidative Stress*
  • Reactive Oxygen Species / metabolism
  • Saccharomyces cerevisiae / drug effects*
  • Saccharomyces cerevisiae / enzymology
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / metabolism


  • Antioxidants
  • Reactive Oxygen Species
  • Saccharomyces cerevisiae Proteins
  • Catalase
  • Superoxide Dismutase
  • Glutathione