Contribution of Yap 1 towards S. cervisiae adaptation to arsenic mediated oxidative stress

Abstract

In the budding yeast Saccharomyces cerevisiae arsenic detoxification involves the activation Yap8, a member of the Yap family of transcription factors, which in turn regulates ACR2 and ACR3, encoding an arsenate reductase and a plasma membrane arsenite efflux-protein, respectively. In addition, Yap1 is involved in the arsenic adaptation process through regulating the expression of the vacuolar-pump encoded by YCF1 and also contributing to the regulation of ACR genes. Here we show that Yap1 is also involved in the removal of ROS generated by arsenic compounds. Data on lipid peroxidation and intracellular oxidation indicate that deletion of YAP1 and YAP8 triggers cellular oxidation mediated by inorganic arsenic. In spite of the increased amounts of As(III) absorbed by the yap8 mutant, the enhanced transcriptional activation of the antioxidant genes such as GSH1, SOD1 and TRX2 may prevent protein oxidation. In contrast, the yap1 mutant exhibits high contents of protein carbonyl groups and the GSSG:GSH ratio is severely disturbed upon exposure to arsenic compounds in these cells. These results point to an additional level of Yap1 contribution to arsenic stress responses by preventing oxidative damage in cells exposed to these compounds. Transcriptional profiling revealed that genes of the functional categories related with sulphur and methionine metabolism and with the maintenance of the cell redox homeostasis are activated to mediate adaptation of the wild type strain to 2 mM arsenate treatment