Caenorhabditis elegans gcs-1 confers resistance to arsenic-induced oxidative stress
Caenorhabditis elegans gcs-1 confers resistance to arsenic-induced oxidative stress
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DOI：
10.1007/s10534-005-2996-3
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发表时间：
2005-10-01
期刊：
影响因子：
3.5
通讯作者：
Yu, CW
中科院分区：
文献类型：
--
作者：
Liao, VHC;Yu, CW
γ-谷氨酰半胱氨酸合成酶 (c-GCS) 催化谷胱甘肽 (GSH) 生物合成的第一个限速步骤。为了评估细胞 GSH 对秀丽隐杆线虫 (C. elegans) 中砷诱导的氧化应激的保护作用，我们检查了 GCS(h) 的线虫直系同源物 gcs-1 对无机砷暴露的反应的作用。我们评估了野生型和gcs-1突变型线虫对无机亚砷酸盐(As(III))和砷酸盐(As(V))离子的反应，发现gcs-1突变型线虫对砷毒性比野生型动物更敏感。杀死一半线虫所需的金属离子量依次为野生型/As(V)> gcs-1/As(V)>野生型/As(III)> gcs-1/As(III)。gcs-1突变线虫对As(III)和As(V)的暴露也比野生型动物表现出更早的反应。与单独用 As(III) 或 As(V) 处理的蠕虫相比，用 GSH 预处理显着提高了 gcs-1 突变蠕虫的存活率。这些结果表明，GCS-1 对于线虫细胞内 GSH 的合成至关重要，因此细胞内 GSH 状态在保护线虫免受砷诱导的氧化应激方面发挥着关键作用。
Gamma-glutamylcysteine synthetase (c-GCS) catalyzes the first, rate-limiting step in the biosynthesis of glutathione (GSH). To evaluate the protective role of cellular GSH against arsenic-induced oxidative stress in Caenorhabditis elegans (C. elegans), we examined the effect of the C. elegans ortholog of GCS(h), gcs-1, in response to inorganic arsenic exposure. We have evaluated the responses of wild-type and gcs-1 mutant nematodes to both inorganic arsenite (As(III)) and arsenate (As(V)) ions and found that gcs-1 mutant nematodes are more sensitive to arsenic toxicity than that of wild-type animals. The amount of metal ion required to kill half of the population of worms falls in the order of wild-type/As(V)> gcs-1/As(V)> wildtype/ As(III)> gcs-1/As(III).gcs-1 mutant nematodes also showed an earlier response to the exposure of As(III) and As(V) than that of wild-type animals. Pretreatment with GSH significantly raised the survival rate of gcs-1 mutant worms compared to As(III)- or As(V)-treated worms alone. These results indicate that GCS-1 is essential for the synthesis of intracellular GSH in C. elegans and consequently that the intracellular GSH status plays a critical role in protection of C. elegans from arsenic-induced oxidative stress.