The role of glutathione transferases in cadmium stress

The role of glutathione transferases in cadmium stress
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DOI:
10.1016/j.toxlet.2004.07.003
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发表时间:
2004-12-01
期刊:
影响因子:
3.5
通讯作者:
Eleutherio, ECA
Eleutherio, ECA
中科院分区:
医学3区
文献类型:
--
作者:
Adamis, PDB;Gomes, DS;Eleutherio, ECA

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利用酿酒酵母作为实验模型,我们观察到GTT 1或GTT 2基因突变的细胞表现出两倍于对照菌株的镉吸收。我们提出,镉-谷胱甘肽复合物的形成是依赖于该转移酶,因为它是以前证明,这种复合物的细胞质水平影响镉的吸收。谷胱甘肽单乙酯(GME),一种模拟谷胱甘肽(GSH)的药物,添加到gtt 1 Delta细胞中,使金属吸收水平恢复到对照菌株的水平。然而,对于gtt 2 Delta细胞,添加GME并没有改变从培养基中去除镉的能力。综上所述,这些结果表明,Gtt 1和Gtt 2在镉解毒机制中发挥不同的作用。通过分析这种金属的毒性效应,我们证实,gtt 2 Delta和gsh 1 Delta细胞分别表现出更高和更低的耐受性镉胁迫比对照细胞,这表明,虽然GSH起着相关的作用,在细胞保护,形成的GSH-Cd共轭物是有害的防御机制。(C)2004爱思唯尔爱尔兰有限公司保留所有权利。
Using Saccharomyces cerevisiae as experimental model, we observed that cells mutated in the GTT1 or GTT2 genes showed twice as much cadmium absorption than the control strain. We proposed that the formation of the cadmium-glutathione complex is dependent on that transferase, since it was previously demonstrated that the cytoplasmic levels of this complex affect cadmium uptake. The addition of glutathione monoethyl ester (GME), a drug that mimics glutathione (GSH), to gtt1 Delta cells restored the levels of metal absorption to those of the control strain. However, with respect to gtt2 Delta cells, addition of GME did not alter the capacity of removing cadmium from the medium. Taken together, these results suggest that Gtt1 and Gtt2 play different roles in the mechanism of cadmium detoxification. By analyzing the toxic effect of this metal, we verified that gtt2 Delta and gsh1 Delta cells showed, respectively, higher and lower tolerance to cadmium stress than control cells, suggesting that although GSH plays a relevant role in cell protection, formation of the GSH-Cd conjugate is deleterious to the mechanism of defense. (C) 2004 Elsevier Ireland Ltd. All rights reserved.