| Co-Investigator(Kenkyū-buntansha) |
IZAWA Shingo Kyoto University, Research Institute for Food Science, Instructor, 食糧科学研究所, 助手 (10273517)
MANO Jun'ichi Kyoto University, Research Institute for Food Science, Instructor, 食糧科学研究所, 助手 (50243100)
INOUE Yoshiharu Kyoto University, Research Institute for Food Science, Associate Professor, 食糧科学研究所, 助教授 (70203263)
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| Research Abstract |
a)Role of thioredoxin in regulation of Yap1 transcription factor in Saccharomyces cerevisiae.
Yap1 is an AP-1-like, b-Zip transcription factor in S. cerevisiae, and it regulates the expression of many genes encoding antioxidant enzymes. Yap1 is concentrated in the nucleus when the yeast cells are exposed to oxidative stress. We found that Yap1 is constitutively concentrated in the nucleus if thioredoxin, a thiol-disulfide oxidoreductase, was disrupted. Intracellular glutathione contents are increased if thioredoxin was destroyed (trx1△/trx2△), however, such a mutant showed increased sensitivity to oxidative stress even though intracellular glutathione levels are high. This was presumably due to the lack of thioredoxin.
b)Role of glutathione in heat shock stress response in yeast.
We found that oxygen respiration rate is increased if the yeast S. cerevisiae cells are shifted to higher temperature, and consequently intracellular oxidation level was increased. Additionally we found that expr
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ession of GSH1 and GSH2, both encoding glutathione-synthesizing enzymes, is increased by heat shock, and intracellular glutathione contents are also increased. In a gsh1 mutant, heat shock treatment induced the respiration deficiency at high rate. These results suggest that the increased production of glutathione under heat shock protects mitochondrial DNA from oxidative damage.
c)Genetic analysis of glutathione peroxidase in S. cerevisiae.
Three glutathione peroxidase (GPx) homologs were found in the yeast S.cerevisiae genome in the genome sequence database of this microorganism. We disrupted each of these homolog genes, and analyzed the function of each gene product. The GPX3 gene was found to be constitutively expressed, and the gpx3△ mutant was hypersensitive to oxidative stress. On the contrary, expression of the GPX2 gene was induced by oxidative stress in a Yap1-dependent fashion. Based on the analysis of the phenotype of a thioredoxin peroxidase mutant (tsal△), the GPX2 gene product was likely to function as a backup system for the thioredoxin peroxidase. Less
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