Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Toxicol Sci. 2010 Dec;118(2):530-43. doi: 10.1093/toxsci/kfq273. Epub 2010 Sep 10.

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

Author information

  • 1Department 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 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.

PMID:
20833709
[PubMed - indexed for MEDLINE]
PMCID:
PMC2984526
Free PMC Article

Images from this publication.See all images (7)Free text

FIG. 1.
FIG. 2.
FIG. 3.
FIG. 4.
FIG. 5.
FIG. 6.
FIG. 7.
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk