Caenorhabditis elegans gcs-1 confers resistance to arsenic-induced oxidative stress.
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.
Liao
Vivian Hsiu-Chuan
VH
Department of Bioenvironmental Systems Engineering, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei 106, Taiwan. vivianliao@ntu.edu.tw
Yu
Chan-Wei
CW
D000818:Animals; D001149:Arsenates / Q000037:antagonists & inhibitors* / Q000633:toxicity; D018053:Arsenites / Q000037:antagonists & inhibitors* / Q000633:toxicity; D017173:Caenorhabditis elegans / Q000187:drug effects / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D024881:Drug Resistance, Bacterial; D005721:Glutamate-Cysteine Ligase / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D005978:Glutathione / Q000096:biosynthesis / Q000494:pharmacology; D009154:Mutation; D018384:Oxidative Stress; D013997:Time Factors
D001149:Arsenates; D018053:Arsenites; D029742:Caenorhabditis elegans Proteins; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione; C015001:arsenite; C025657:arsenic acid