Inoue Y, Matsuda T, Sugiyama K, Izawa S, Kimura A
Research Institute for Food Science, Kyoto University, Uji, Kyoto 611-0011, Japan.
J Biol Chem. 1999 Sep 17;274(38):27002-9. doi: 10.1074/jbc.274.38.27002.
Three glutathione peroxidase homologs (YKL026C, YBR244W, and YIR037W/HYR1) were found in the Saccharomyces Genome Database. We named them GPX1, GPX2, and GPX3, respectively, and we investigated the function of each gene product. The gpx3Delta mutant was hypersensitive to peroxides, whereas null mutants of the GPX1 and GPX2 did not show any obvious phenotypes. Glutathione peroxidase activity decreased approximately 57 and 93% in the gpx3Delta and gpx1Delta/gpx2Delta/gpx3Delta mutants, respectively, compared with that of wild type. Expression of the GPX3 gene was not induced by any stresses tested, whereas that of the GPX1 gene was induced by glucose starvation. The GPX2 gene expression was induced by oxidative stress, which was dependent upon the Yap1p. The TSA1 (thiol-specific antioxidant) gene encodes thioredoxin peroxidase that can reduce peroxides by using thioredoxin as a reducing power. Disruption of the TSA1 gene enhanced the basal expression level of the Yap1p target genes such as GSH1, GLR1, and GPX2 and that resulted in increases of total glutathione level and activities of glutathione reductase and glutathione peroxidase. However, expression of the TSA1 gene did not increase in the gpx1Delta/gpx2Delta/gpx3Delta mutant. Therefore, de novo synthesis and recycling of glutathione were increased in the tsa1Delta mutant to maintain the catalytic cycle of glutathione peroxidase reaction efficiently as a backup system for thioredoxin peroxidase.
在酵母基因组数据库中发现了三种谷胱甘肽过氧化物酶同源物（YKL026C、YBR244W和YIR037W/HYR1）。我们分别将它们命名为GPX1、GPX2和GPX3，并对每个基因产物的功能进行了研究。gpx3Delta突变体对过氧化物高度敏感，而GPX1和GPX2的缺失突变体未表现出任何明显的表型。与野生型相比，gpx3Delta和gpx1Delta/gpx2Delta/gpx3Delta突变体中的谷胱甘肽过氧化物酶活性分别降低了约57%和93%。GPX3基因的表达不受任何测试应激的诱导，而GPX1基因的表达受葡萄糖饥饿诱导。GPX2基因的表达受氧化应激诱导，这依赖于Yap1p。TSA1（硫醇特异性抗氧化剂）基因编码硫氧还蛋白过氧化物酶，它可以利用硫氧还蛋白作为还原力来还原过氧化物。TSA1基因的破坏增强了Yap1p靶基因如GSH1、GLR1和GPX2的基础表达水平，这导致总谷胱甘肽水平以及谷胱甘肽还原酶和谷胱甘肽过氧化物酶活性增加。然而，TSA1基因在gpx1Delta/gpx2Delta/gpx3Delta突变体中的表达并未增加。因此，tsa1Delta突变体中谷胱甘肽的从头合成和循环增加，以有效地维持谷胱甘肽过氧化物酶反应的催化循环，作为硫氧还蛋白过氧化物酶的备用系统。
