The yeast Saccharomyces cerevisiae, devoid of selenoproteins, can be considered as a convenient model for studies of selenite toxicity, without any interfering impact of selenoproteins. In this microorganism, dual effects of selenium have been demostrated. At micromolar concentrations, selenite suppresses mutagenesis while having toxic effects in the milimolar concentration range. Selenite toxicity in the yeast is thought to be closely related to its prooxidant action. Se(IV), behaving as an oxidant, can induce oxidative stress response genes such as GLR1 (encoding for glutathione reductase) and TRR1 (encoding for thioredoxin reductase) in a YAP1-dependent manner. Overexpression of glutathione reductase also confers resistance to selenite. We examined how the disruption of genes encoding for antioxidant proteins, glutaredoxins, GRX1 or GRX2 or GRX5 genes, can affect selenite toxicity in yeast. We found that the Δgrx1Δgrx2 and the Δgrx5 disruptants were hypersensitive to selenite treatment. Exogenous antioxidants, affecting cell redox homeostasis, can protect against the harmful effects of Se(VI). Thiols (glutathione, L-cysteine, N-acetylcysteine and dithiothreitol) followed by ascorbate were the most effective antioxidants in the growth restoration assay. Tempol, Trolox and melatonin showed no protective effect. Augmentation of the intracellular levels of two endogenous antioxidants, erythroascorbic acid (a five-carbon ascorbic acid analog synthesized in the yeast) and glutathione confers resistance to selenite. We found elevation in intracellular peroxide (P<0.01) and superoxide (P<0.001) production in the Δgrx1Δgrx2 and the Δgrx5 mutants after Se(IV) treatment, estimated by oxidation of 2’,7’-dichlorodihydrofluorescein and dihydroethidine, respectively. Augmentation in intracellular mitochondrial superoxide production, estimated by the rate of increase of MitoTracker® Red CMXRos fluorescence after selenite exposure, was also seen and was more pronounced for cells lacking the mitochondrial Grx5 protein (P<0.01). Collectively, our data demonstrate that hypersensitivity to the Δgrx1Δgrx2 and the Δgrx5 disruptants to selenite is mediated by altered redox equilibrium.

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