Caenorhabditis elegans之gcs-1基因與砷造成之氧化壓力之探討
Caenorhabditis elegans gcs-1 confers resistance to arsenic-induced oxidative stress
Date Issued
2007
Date
2007
Author(s)
Yu, Chan-Wei
DOI
en-US
Abstract
Gamma-glutamylcysteine synthetase (γ-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. 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. The intracellular GSH level increases in C. elegans exposed to As(III) and gcs-1 expression level is induced by As(III). The functional importantance of GCS-1 in C. elegans exposed to As(III) is investigated by analysis of gcs-1 transcription in transgenic C. elegans and RNAi mediated GCS-1 knock-down worms. The level of mRNA expression of several potential oxidative response gene is response to As(III) exposure was also investigated. Our results show 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. Furthermore, As(III) is capable of inducing mRNA expression of oxidative stress-related genes.
Subjects
Gamma-glutamylcysteine synthetase
glutathione
Caenorhabditis elegans
砷
氧化壓力
arsenic
Type
thesis
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