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 -