The H sub(2)O sub(2) Stimulon in Saccharomyces cerevisiae

The changes in gene expression underlying the yeast adaptive stress response to H sub(2)O sub(2) were analyzed by comparative two-dimensionalgel electrophoresis of total cell proteins. The synthesis of at least 115 proteins is stimulated by H sub(2)O sub(2), whereas 52 other proteins are repressed by this treatment. We have identified 71 of the stimulated and 44 of the repressed targets. The kinetics and dose-response parameters of the H sub(2)O sub(2) genomic response were also analyzed. Identification of these proteins and their mapping into specific cellular processes give a distinct picture of the way in which yeast cells adapt to oxidative stress. As expected, H sub(2)O sub(2)- responsive targets include an important number of heat shock proteins and proteins with reactive oxygen intermediate scavenging activities. Exposure to H sub(2)O sub(2) also results in a slowdown of protein biosynthetic processes and a stimulation of protein degradation pathways. Finally, the most remarkable result inferred from this study is the resetting of carbohydrate metabolism minutes after the exposure to H sub(2)O sub(2). Carbohydrate fluxes are redirected to the regeneration of NADPH at the expense of glycolysis. This study represents the first genome-wide characterization of a H sub(2)O sub(2)- inducible stimulon in a eukaryote.