Deletion of thioredoxin reductase and effects of selenite and selenate toxicity in Caenorhabditis elegans.
Thioredoxin reductase-1 (TRXR-1) is the sole selenoprotein in C. elegans, and selenite is a substrate for thioredoxin reductase, so TRXR-1 may play a role in metabolism of selenium (Se) to toxic forms. To study the role of TRXR in Se toxicity, we cultured C. elegans with deletions of trxr-1, trxr-2, and both in axenic media with increasing concentrations of inorganic Se. Wild-type C. elegans cultured for 12 days in Se-deficient axenic media grow and reproduce equivalent to Se-supplemented media. Supplementation with 0-2 mM Se as selenite results in inverse, sigmoidal response curves with an LC50 of 0.20 mM Se, due to impaired growth rather than reproduction. Deletion of trxr-1, trxr-2 or both does not modulate growth or Se toxicity in C. elegans grown axenically, and (75)Se labeling showed that TRXR-1 arises from the trxr-1 gene and not from bacterial genes. Se response curves for selenide (LC50 0.23 mM Se) were identical to selenite, but selenate was 1/4(th) as toxic (LC50 0.95 mM Se) as selenite and not modulated by TRXR deletion. These nutritional and genetic studies in axenic media show that Se and TRXR are not essential for C. elegans, and that TRXR alone is not essential for metabolism of inorganic Se to toxic species.
Department of Nutritional Sciences, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
Christopher J
CJ
Boehler
Anna M
AM
Raines
Roger A
RA
Sunde
D000818:Animals; D017173:Caenorhabditis elegans / Q000187:drug effects* / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development; D055786:Gene Knockout Techniques; D008297:Male; D064586:Selenic Acid / Q000633:toxicity*; D020887:Selenious Acid / Q000633:toxicity*; D054481:Thioredoxin Reductase 1 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D054482:Thioredoxin Reductase 2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D013880:Thioredoxin-Disulfide Reductase / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism
D054481:Thioredoxin Reductase 1; D054482:Thioredoxin Reductase 2; D013880:Thioredoxin-Disulfide Reductase; D020887:Selenious Acid; D064586:Selenic Acid