THE H2O2 STIMULON IN SACCHAROMYCES-CEREVISIAE

The changes in gene expression underlying the yeast adaptive stress re sponse to H2O2 were analyzed by comparative two-dimensional gel electr ophoresis of total cell proteins. The synthesis of at least 115 protei ns is stimulated by H2O2, whereas 52 other proteins are repressed by t his treatment. We have identified 71 of the stimulated and 44 of the r epressed targets. The kinetics and dose-response parameters of the H2O 2, genomic response were also analyzed. Identification of these protei ns and their mapping into specific cellular processes give a distinct picture of the way in which yeast cells adapt to oxidative stress. As expected, H2O2-responsive targets include an important number of heat shock proteins and proteins with reactive oxygen intermediate scavengi ng activities. Exposure to H2O2 also results in a slowdown of protein biosynthetic processes and a stimulation of protein degradation pathwa ys. Finally, the most remarkable result inferred from this study is th e resetting of carbohydrate metabolism minutes after the exposure to H 2O2. Carbohydrate fluxes are redirected to the regeneration of NADPH a t the expense of glycolysis. This study represents the first genome-wi de characterization of a H2O2-inducible stimulon in a eukaryote.