Liao Vivian Hsiu-Chuan, Yu Chan-Wei
Department of Bioenvironmental Systems Engineering, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei 106, Taiwan.
Biometals. 2005 Oct;18(5):519-28. doi: 10.1007/s10534-005-2996-3.
Gamma-glutamylcysteine synthetase (gamma-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)> wild-type/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.
γ-谷氨酰半胱氨酸合成酶（γ-GCS）催化谷胱甘肽（GSH）生物合成的第一步，也是限速步骤。为了评估细胞内GSH对秀丽隐杆线虫中砷诱导的氧化应激的保护作用，我们研究了秀丽隐杆线虫GCS（h）的直系同源基因gcs-1在无机砷暴露后的反应。我们评估了野生型和gcs-1突变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突变线虫比野生型动物对砷毒性更敏感。杀死半数线虫群体所需的金属离子量顺序为野生型/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）暴露的反应也比野生型动物更早。与单独用As（III）或As（V）处理的线虫相比，用GSH预处理显著提高了gcs-1突变线虫的存活率。这些结果表明，GCS-1对于秀丽隐杆线虫细胞内GSH的合成至关重要，因此细胞内GSH状态在保护秀丽隐杆线虫免受砷诱导的氧化应激中起着关键作用。
