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Oxidative stress is caused by an imbalance between the production of reactive oxygen and a biological system's ability to detoxify the reactive oxygen molecules produced. Reactive oxygen molecules take electrons from other molecules causing oxidative stress. Oxidative stress can cause cancer, neurodegenerative disease, and cardiovascular disease. These reactive oxygen molecules are hydrogen peroxide (H2O2), superoxide anions (O2-), and hydroxyl radicals (OH-). These reactive species can break DNA strands as well as damage essential enzymes, proteins, and cell membranes when in contact with them. Oxidative stress has been linked to the pathogenesis of cancer, cardiovascular disease, atherosclerosis, hypertension, ischemia/reperfusion injury, diabetes mellitus, neurodegenerative diseases (Alzheimer's disease and Parkinson's disease), rheumatoid arthritis, and ageing (Valko 2007). Antioxidants inhibit damage from reactive oxygen molecules by removing free radical intermediates and inhibiting other oxidation reactions by being oxidized themselves. One anti-oxidant factor is Glucose 6-phosphate dehydrogenase (G6PD). This particular anti-oxidant is part of the Pentose Phosphate Pathway and catalyzes the oxidation of NADP to become NADPH, which is a source of electrons for the cell. A correlation has been seen when G6PD levels in rat brains decreases the reactive oxygen molecule levels increase (Mishra 2008).
Eukaryotes have very conserved genes, which code for anti-oxidant factors like G6PD. Saccharomyces cerevisiae, bakers yeast, is a unicellular eukaryote as well as a model organism with many characteristics that make it ideal for this study. One characteristic is that it can be used in a haploid state where knockout genes only need to be knocked out once because there is not a second allele. In addition, Saccharomyces cerevisiae contains typical anti-oxidant genes found in all eukaryotes. Previous studies have knocked out zwf1 and discovered phenotypes, which characterize this knockout mutant of yeast. The characteristics include sensitivity to oxygen, oxidizing agents and aerobic methionine auxotrophy. The genes zms1 and zms2 were found to be functionally related to zwf1 as well as encode for potential zinc-finger transcription factors (Slekar, 2008). When genes zms1 and zms2 are over expressed in zwf1 knockout mutants they suppress the zwf1∆ mutation. These genes are thought to be suppressors of the zwf1D mutants.
In the present study zms1∆ and zms2∆ single knockout mutants of yeast strains and zms1∆zms2∆ double knockout mutant yeast strains were compared to wild-type yeast strains using Microarray techniques and analysis. The zms1 and zms2 genes are associated with and aid to relieve oxidative stress. It is hypothesized that the genes found to be expressed differently will be related to oxidative stress relief and possibly a direct result of over or under expression from the remaining oxidative stress genes picking up the slack.