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The glutaredoxin GLRX-21 functions to prevent selenium-induced oxidative stress in Caenorhabditis elegans.

Morgan KL, Estevez AO, Mueller CL, Cacho-Valadez B, Miranda-Vizuete A, Szewczyk NJ, Estevez M - Toxicol. Sci. (2010)

Bottom Line: The C elegans glrx-21 gene belongs to the family of glutaredoxins (glutathione-dependent oxidoreductases) and the glrx-21(tm2921) allele is a 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Veterans Affairs Pittsburgh Healthcare System, Research and Development (151U), University Drive C, Pittsburgh, Pennsylvania 15240, USA.

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 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.

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Selenium is both protective and toxic to Caenorhabditis elegans. The effects on the survival of wild-type animals exposed to increasing Na2SeO3 concentrations (0–10mM) either alone (•) or in the presence of 1mM (Δ) or 2mM (▴) H2O2. Each dataset represents the averages of six to nine plates with 10 animals per plate exposed in liquid for 12 h and is presented as the mean percentage of dead animals ± SD. The LC50 for Na2SeO3 exposure at 12 h was calculated to be 3.47mM. #p < 0.05, compared with 2mM H2O2 and 1mM Na2SeO3; ##p < 0.05, compared with 1mM H2O2 (no significant difference to 2mM Na2SeO3); * p < 0.01, compared with both 1mM H2O2 and either 0.001 or 0.01mM Na2SeO3; **p < 0.001, compared with 1mM H2O2 (no significant difference to 1mM Na2SeO3).
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fig1: Selenium is both protective and toxic to Caenorhabditis elegans. The effects on the survival of wild-type animals exposed to increasing Na2SeO3 concentrations (0–10mM) either alone (•) or in the presence of 1mM (Δ) or 2mM (▴) H2O2. Each dataset represents the averages of six to nine plates with 10 animals per plate exposed in liquid for 12 h and is presented as the mean percentage of dead animals ± SD. The LC50 for Na2SeO3 exposure at 12 h was calculated to be 3.47mM. #p < 0.05, compared with 2mM H2O2 and 1mM Na2SeO3; ##p < 0.05, compared with 1mM H2O2 (no significant difference to 2mM Na2SeO3); * p < 0.01, compared with both 1mM H2O2 and either 0.001 or 0.01mM Na2SeO3; **p < 0.001, compared with 1mM H2O2 (no significant difference to 1mM Na2SeO3).

Mentions: Selenium is a required micronutrient that has been highly publicized for its antioxidant activity and its potential role to both treat and prevent diseases (Facompre and El-Bayoumy, 2009; Reeves and Hoffmann, 2009). Yet, chronic exposures to doses as low as 400 μg/day (the upper limit for consumption) may induce toxicity in sensitive individuals (Lemly, 1997). To test whether selenium is toxic to C elegans, adult N2 wild-type animals were exposed to various nominal concentrations of sodium selenite (Na2SeO3) diluted in dH2O and then scored after 12 h at 20°C to determine the percentage of dead animals per plate (lethality assay). Under these conditions, selenium exhibited a dose-dependent increase in lethality that was most apparent with exposures above 1mM (Figure 1).


The glutaredoxin GLRX-21 functions to prevent selenium-induced oxidative stress in Caenorhabditis elegans.

Morgan KL, Estevez AO, Mueller CL, Cacho-Valadez B, Miranda-Vizuete A, Szewczyk NJ, Estevez M - Toxicol. Sci. (2010)

Selenium is both protective and toxic to Caenorhabditis elegans. The effects on the survival of wild-type animals exposed to increasing Na2SeO3 concentrations (0–10mM) either alone (•) or in the presence of 1mM (Δ) or 2mM (▴) H2O2. Each dataset represents the averages of six to nine plates with 10 animals per plate exposed in liquid for 12 h and is presented as the mean percentage of dead animals ± SD. The LC50 for Na2SeO3 exposure at 12 h was calculated to be 3.47mM. #p < 0.05, compared with 2mM H2O2 and 1mM Na2SeO3; ##p < 0.05, compared with 1mM H2O2 (no significant difference to 2mM Na2SeO3); * p < 0.01, compared with both 1mM H2O2 and either 0.001 or 0.01mM Na2SeO3; **p < 0.001, compared with 1mM H2O2 (no significant difference to 1mM Na2SeO3).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2984526&req=5

fig1: Selenium is both protective and toxic to Caenorhabditis elegans. The effects on the survival of wild-type animals exposed to increasing Na2SeO3 concentrations (0–10mM) either alone (•) or in the presence of 1mM (Δ) or 2mM (▴) H2O2. Each dataset represents the averages of six to nine plates with 10 animals per plate exposed in liquid for 12 h and is presented as the mean percentage of dead animals ± SD. The LC50 for Na2SeO3 exposure at 12 h was calculated to be 3.47mM. #p < 0.05, compared with 2mM H2O2 and 1mM Na2SeO3; ##p < 0.05, compared with 1mM H2O2 (no significant difference to 2mM Na2SeO3); * p < 0.01, compared with both 1mM H2O2 and either 0.001 or 0.01mM Na2SeO3; **p < 0.001, compared with 1mM H2O2 (no significant difference to 1mM Na2SeO3).
Mentions: Selenium is a required micronutrient that has been highly publicized for its antioxidant activity and its potential role to both treat and prevent diseases (Facompre and El-Bayoumy, 2009; Reeves and Hoffmann, 2009). Yet, chronic exposures to doses as low as 400 μg/day (the upper limit for consumption) may induce toxicity in sensitive individuals (Lemly, 1997). To test whether selenium is toxic to C elegans, adult N2 wild-type animals were exposed to various nominal concentrations of sodium selenite (Na2SeO3) diluted in dH2O and then scored after 12 h at 20°C to determine the percentage of dead animals per plate (lethality assay). Under these conditions, selenium exhibited a dose-dependent increase in lethality that was most apparent with exposures above 1mM (Figure 1).

Bottom Line: The C elegans glrx-21 gene belongs to the family of glutaredoxins (glutathione-dependent oxidoreductases) and the glrx-21(tm2921) allele is a 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Veterans Affairs Pittsburgh Healthcare System, Research and Development (151U), University Drive C, Pittsburgh, Pennsylvania 15240, USA.

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 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.

Show MeSH
Related in: MedlinePlus