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

TY - JOUR

T1 - Antioxidant small molecules confer variable protection against oxidative damage in yeast mutants

AU - Amari, Foued

AU - Fettouche, Abdelmadjid

AU - Samra, Mario Abou

AU - Kefalas, Panagiotis

AU - Kampranis, Sotirios

AU - Makris, Antonios M

PY - 2008

Y1 - 2008

N2 - 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.

AB - 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.

KW - Antioxidants

KW - Catalase

KW - Glutathione

KW - Microbial Viability

KW - Mutation

KW - Oxidative Stress

KW - Reactive Oxygen Species

KW - Saccharomyces cerevisiae

KW - Saccharomyces cerevisiae Proteins

KW - Superoxide Dismutase

U2 - 10.1021/jf802829r

DO - 10.1021/jf802829r

M3 - Journal article

C2 - 19049288

SN - 0021-8561

VL - 56

SP - 11740

EP - 11751

JO - Journal of Agricultural and Food Chemistry

JF - Journal of Agricultural and Food Chemistry

IS - 24

ER -