Two putative selenium binding proteins as modulators of C. elegans stress response and life span

Selenium-binding proteins do not contain selenium in the form of selenocysteine or selenomethionine but as inorganic selenium bound to the protein. The C. elegans genome encodes only one selenocysteine-containing selenoprotein, TrxR-1. However, at least two ORFs encode putative selenium-binding proteins, CeSELENBP1 and CeSELENBP2. These are 54% and 36% homologous to human selenium-binding protein-1 (SELENBP1), respectively, and both contain a cysteine residue hypothesized to bind selenite as in SELENBP1. Considering the role of selenium in antioxidant defence, we hypothesized that CeSELENBP1 and CeSELENBP2 may modulate the response of C. elegans to oxidative stress. Unexpectedly, life-long knock-down of either of the genes significantly increased life span and stress resistance to the redox cycler paraquat. DAF-16 and SKN-1 are key players in the C. elegans stress response that are known to mediate many of the published life-extending effects of chemical compounds, phytochemicals and nutrition regimens. However, RNAi against CeSELENBP1 and CeSELENBP2 significantly increased life span of the mutants to an extent similar to that found in wild type worms exposed to RNAi targeting either of the putative selenium binding proteins. This suggests that neither DAF-16 nor SKN-1 are involved in life span extension elicited by knock-down of CeSELENBP1 and CeSELENBP2.