RRC ID 7164
著者 Morgan KL, Estevez AO, Mueller CL, Cacho-Valadez B, Miranda-Vizuete A, Szewczyk NJ, Estevez M.
タイトル The glutaredoxin GLRX-21 functions to prevent selenium-induced oxidative stress in Caenorhabditis elegans.
ジャーナル Toxicol Sci
Abstract Selenium is an essential micronutrient that functions as an antioxidant. Yet, at higher concentrations, selenium is pro-oxidant and toxic. In extreme cases, exposures to excess selenium can lead to death or selenosis, a syndrome characterized by teeth, hair and nail loss, and nervous system alterations. Recent interest in selenium as an anti- tumorigenic agent has reemphasized the need to understand the mechanisms underlying the cellular consequences of increased selenium exposure. We show here, that in the nematode, Caenorhabditis elegans, selenium has a concentration range in which it functions as an antioxidant, but beyond this range it exhibits a dose- and time-dependent lethality. Oxidation-induced fluorescence emitted by the dye, carboxy-H(2)DCFDA, indicative of reactive oxygen species formation was significantly higher in animals after a brief exposure to 5mM sodium selenite. Longer-term exposures lead to a progressive selenium-induced motility impairment that could be partially prevented by coincident exposure to the cellular antioxidant-reduced glutathione. The C elegans glrx-21 gene belongs to the family of glutaredoxins (glutathione-dependent oxidoreductases) and the glrx-21(tm2921) allele is a null mutation that renders animals hypersensitive for the selenium-induced motility impairment, but not lethality. In addition, the lethality of animals with the tm2921 mutation exposed to selenium was unaffected by the addition of reduced glutathione, suggesting that GLRX-21 is required for glutathione to moderate this selenium-induced lethality. Our findings provide the first description of selenium-induced toxicity in C elegans and support its use as a model for elucidating the mechanisms of selenium toxicity.
巻・号 118(2)
ページ 530-43
公開日 2010-12-1
DOI 10.1093/toxsci/kfq273
PII kfq273
PMID 20833709
PMC PMC2984526
MeSH Animal Testing Alternatives Animals Animals, Genetically Modified Antioxidants / toxicity* Caenorhabditis elegans / drug effects* Caenorhabditis elegans / metabolism Disease Models, Animal Dose-Response Relationship, Drug Gene Expression / drug effects Glutaredoxins / genetics Glutaredoxins / metabolism* Longevity / drug effects Movement / drug effects Oxidative Stress / drug effects* RNA, Messenger / metabolism Reactive Oxygen Species / metabolism Sequence Analysis, Protein Sodium Selenite / toxicity* Time Factors Toxicity Tests, Acute
IF 3.703
引用数 35
WOS 分野 TOXICOLOGY
リソース情報
線虫 tm2921