Adamis Paula D B, Gomes Débora S, Pinto Maria Lucia C C, Panek Anita D, Eleutherio Elis C A
Departamento de Bioquímica, IQ, UFRJ, Rio de Janeiro, RJ, Brazil.
Toxicol Lett. 2004 Dec 1;154(1-2):81-8. doi: 10.1016/j.toxlet.2004.07.003.
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 gtt1Delta cells restored the levels of metal absorption to those of the control strain. However, with respect to gtt2Delta 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 gtt2Delta and gsh1Delta 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.
以酿酒酵母作为实验模型，我们观察到GTT1或GTT2基因发生突变的细胞对镉的吸收量是对照菌株的两倍。我们推测镉 - 谷胱甘肽复合物的形成依赖于那种转移酶，因为先前已证明该复合物的细胞质水平会影响镉的摄取。向gtt1Delta细胞中添加模拟谷胱甘肽（GSH）的药物谷胱甘肽单乙酯（GME），可使金属吸收水平恢复到对照菌株的水平。然而，对于gtt2Delta细胞，添加GME并未改变从培养基中去除镉的能力。综上所述，这些结果表明Gtt1和Gtt2在镉解毒机制中发挥不同作用。通过分析这种金属的毒性作用，我们证实gtt2Delta和gsh1Delta细胞分别比对照细胞对镉胁迫表现出更高和更低的耐受性，这表明尽管GSH在细胞保护中发挥相关作用，但GSH - Cd共轭物的形成对防御机制是有害的。
