[
International Worm Meeting,
2007]
Glutathione (GSH) plays a critical role in protecting cells against endogenous and exogenous oxidative stress. Glutathione synthetase (GS) catalyzes the second step in the biosynthesis of GSH. To investigate the protective role of cellular GSH against arsenic-induced oxidative stress in C. elegans, we examined the effect of the C. elegans ortholog of GS-1 (M176.2) in response to inorganic arsenic exposure. Under normal standard growth conditions, pleiotropic phenotypes of gs-1 (RNAi) worms were observed, including slow growth, morphological change, slow life span, and reduced brood size, suggesting that gs-1 is essential for development and viability. These observed effects were more profound while gs-1 (RNAi) worms were grown in the presence of As(III), indicating that GS-1 is required C. elegans'' defense against As(III) toxicity. Level of GS-1 mRNA varied in different developmental stages of worms and the highest level of GS-1 mRNA was observed at L4-stage. Whereas GS-1 mRNA at L1-stage exhibited the highest induction ratio after 1 h of As(III) exposure. Transcription of gs-1 was observed in pharynx and intestinal cells of post-embryonic C. elegans. Heat, paraquat, and Cd(II) significantly induced gs-1 expression with the highest level GFP signal at L1-stage, whereas As(III) induced less extent. Our results indicated that GS-1 plays an important role in C. elegans development and it is required for the protection of C. elegans against arsenic-induced oxidative stress.