The Glutaredoxin GLRX-21 Functions to Prevent Selenium-Induced Oxidative Stress in Caenorhabditis elegans
| Autor: | Antonio Miranda-Vizuete, Briseida Cacho-Valadez, Catherine L. Mueller, Kathleen L. Morgan, Nathaniel J. Szewczyk, Annette O. Estevez, Miguel Estevez |
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| Rok vydání: | 2010 |
| Předmět: |
Time Factors
antioxidant Antioxidant medicine.medical_treatment Glutaredoxin Gene Expression 010501 environmental sciences Toxicology medicine.disease_cause 01 natural sciences Antioxidants Animals Genetically Modified chemistry.chemical_compound Sequence Analysis Protein Caenorhabditis elegans Genetics chemistry.chemical_classification 0303 health sciences biology food and beverages Glutathione Glrx-21 3. Good health Cell biology Toxicity inorganic chemicals Movement Longevity chemistry.chemical_element Animal Testing Alternatives 03 medical and health sciences Selenium Sodium Selenite Molecular Toxicology Toxicity Tests Acute medicine Animals RNA Messenger Glutaredoxins 030304 developmental biology 0105 earth and related environmental sciences Reactive oxygen species Dose-Response Relationship Drug biology.organism_classification Disease Models Animal Oxidative Stress chemistry Reactive Oxygen Species Oxidative stress |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname Toxicological Sciences |
| Popis: | 14 páginas, 7 figuras, 1 tabla.-- This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License. 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-H2DCFDA, 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. This work was supported by a Career Development Award (M.E.) provided through the Office of Research and Development, Department of Veterans Affairs, the National Institutes of Environmental Health Sciences (R21-ES012305 to A.E. and M.E.) and Arthritis and Musculoskeletal and Skin Diseases (R01-AR054342 to N.J.S.), the Instituto de Salud Carlos III (Projects PI050065 and PI080557, co-financed with the Fondo Social Europeo, FEDER) and Junta de Andalucía (Projects P07-CVI-02697 and P08-CVI-03629), Spain (A.M.-V.) and a predoctoral fellowship from CONACYT, Mexico (B.C.-V.). |
| Databáze: | OpenAIRE |
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