Na+依赖性谷氨酸和天冬氨酸转运体支持谷胱甘肽维持和CHO-K1细胞的存活。

R P Igo, J F Ash
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引用次数: 12

摘要

谷胱甘肽合成是一个重要的细胞过程,依赖于氨基酸转运体系统x-C对l -胱氨酸的摄取。本研究表明,通过CHO-K1体细胞突变体,第二种转运体System X-AG是正常System x-C活性和谷胱甘肽维持所必需的。无论是在对照条件下还是在长时间的亲电试剂处理后,两个X-AG-null突变体中System x-C的摄取明显低于CHO-K1。此外,对照和处理突变细胞中的谷胱甘肽水平低于野生型CHO-K1或假逆转细胞的一半。这种减少的意义是通过化学挑战测试的:突变体对苯基苯并醌产生的活性氧和抗癌药物顺铂产生的损伤的敏感性是野生型的两倍。这些结果表明,系统X-AG提供了大量的谷氨酸,用于激活合成谷胱甘肽所需的胱氨酸的摄取。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The Na+-dependent glutamate and aspartate transporter supports glutathione maintenance and survival of CHO-K1 cells.

Glutathione synthesis, a vital cellular process, depends on L-cystine uptake by the amino acid transporter, System x-C. Here we show that a second transporter, System X-AG, is required for normal System x-C activity and glutathione maintenance by employing somatic cell mutants of CHO-K1. Uptake by System x-C in two X-AG-null mutants is significantly lower than that of CHO-K1, either under control conditions or after prolonged treatment with an electrophile. In addition, levels of glutathione in control and treated mutant cells are less than half those of wild-type CHO-K1 or of a pseudorevertant. The significance of this reduction was tested by chemical challenge: mutants are twofold more sensitive than wild type to reactive oxygen species generated by phenylbenzoquinone and to damage produced by the anticancer drug, cisplatin. These results suggest that System X-AG provides a significant portion of the glutamate used to energize the uptake of cystine required for the synthesis of glutathione.

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