Vido K, Spector D, Lagniel G, Lopez S, Toledano M B, Labarre J
Service de Biochimie et Génétique Moléculaire, Bât 142, CEA-Saclay, F-91191, Gif-sur-Yvette Cedex, France.
J Biol Chem. 2001 Mar 16;276(11):8469-74. doi: 10.1074/jbc.M008708200. Epub 2000 Nov 14.
Cadmium is very toxic at low concentrations, but the basis for its toxicity is not clearly understood. We analyzed the proteomic response of yeast cells to acute cadmium stress and identified 54 induced and 43 repressed proteins. A striking result is the strong induction of 9 enzymes of the sulfur amino acid biosynthetic pathway. Accordingly, we observed that glutathione synthesis is strongly increased in response to cadmium treatment. Several proteins with antioxidant properties were also induced. The induction of nine proteins is dependent upon the transactivator Yap1p, consistent with the cadmium hypersensitive phenotype of the YAP1-disrupted strain. Most of these proteins are also overexpressed in a strain overexpressing Yap1p, a result that correlates with the cadmium hyper-resistant phenotype of this strain. Two of these Yap1p-dependent proteins, thioredoxin and thioredoxin reductase, play an important role in cadmium tolerance because strains lacking the corresponding genes are hypersensitive to this metal. Altogether, our data indicate that the two cellular thiol redox systems, glutathione and thioredoxin, are essential for cellular defense against cadmium.
镉在低浓度时就具有很强的毒性，但其毒性的基础尚不清楚。我们分析了酵母细胞对急性镉胁迫的蛋白质组学反应，鉴定出54种诱导蛋白和43种抑制蛋白。一个显著的结果是，硫氨基酸生物合成途径中的9种酶被强烈诱导。因此，我们观察到，镉处理后谷胱甘肽的合成显著增加。几种具有抗氧化特性的蛋白质也被诱导。9种蛋白质的诱导依赖于反式激活因子Yap1p，这与YAP1缺失菌株的镉超敏表型一致。这些蛋白质中的大多数在过表达Yap1p的菌株中也过表达，这一结果与该菌株的镉超抗性表型相关。这两种依赖Yap1p的蛋白质，即硫氧还蛋白和硫氧还蛋白还原酶，在镉耐受性中起重要作用，因为缺乏相应基因的菌株对这种金属超敏。总之，我们的数据表明，细胞内的两个硫醇氧化还原系统，即谷胱甘肽和硫氧还蛋白，对于细胞抵御镉至关重要。
