Selenite-induced Expression of a Caenorhabditis elegans Pro-aging Factor and Ortholog of Human Selenium-binding Protein 1

Abstract

Background: The essential trace element and micronutrient selenium exerts most of its biological actions through incorporation into selenoproteins as selenocysteine. Two further types of Se-containing proteins exist, including those that have selenomethionine incorporated instead of methionine, and the group of selenium-binding proteins. We previously described an ortholog of selenium-binding protein 1 (SELENBP1) in the nematode Caenorhabditis elegans, Y37A1B.5, and demonstrated that it confers resistance to toxic selenite concentrations while impairing general stress resistance and life expectancy of C. elegans. Objective: We tested for the effect of selenite on Y37A1B.5 expression, and we analyzed whether Y37A1B.5 also shows a lifespan-modulating effect when the nematodes are deficient in the selenoenzyme thioredoxin reductase-1 (TRXR-1). Methods: C. elegans expressing a translational reporter construct encoding GFP-tagged Y37A1B.5 under the control of the Y37A1B.5 promoter were exposed to selenite, followed by fluorescence microscopic analysis of GFP levels. Lifespan analyses and RNA interference experiments were performed in trxr-1-deficient worms. Results: We here demonstrate that selenite at toxic concentrations stimulates the expression of the translational Y37A1B.5 reporter. The lifespan-extending effect of Y37A1B.5 deficiency was preserved upon the deletion of the only selenoprotein in C. elegans, TRXR-1. Conclusion: These data suggest that (1) Y37A1B.5 may serve as a selenite-responsive buffer against high environmental selenium concentrations and that (2) lifespan extension elicited by Y37A1B.5 knockdown does not require functional TRXR-1.

SEMO‐1, a novel methanethiol oxidase in Caenorhabditis elegans, is a pro‐aging factor conferring selective stress resistance

“…15 Selenite, in turn, stimulated the expression of this SELENBP1 ortholog. 16 Using a newly generated C. elegans strain deficient in Y37A1B.5, we here demonstrate that Y37A1B.5 is an MTO; Y37A1B.5 is therefore renamed SEMO-1 (SELENBP1 ortholog with methanethiol oxidase activity). Moreover, SEMO-1-deficient worms showed an extended life span and elevated tolerance to oxidative stress but lower selenite resistance.…”

“…Y37A1B.5 appears to be involved in the regulation of aging processes in the nematode: levels of Y37A1B.5 mRNA decreased with age; moreover, knockdown through RNA interference resulted in a ~10% increase in life span and enhanced resistance of the worms to oxidative stress, whereas their survival in the presence of high selenite concentrations was attenuated 15 . Selenite, in turn, stimulated the expression of this SELENBP1 ortholog 16 . Using a newly generated C. elegans strain deficient in Y37A1B.5 , we here demonstrate that Y37A1B.5 is an MTO; Y37A1B.5 is therefore renamed SEMO‐1 (SELENBP1 ortholog with methanethiol oxidase activity).…”

A coupled enzyme assay for detection of selenium-binding protein 1 (SELENBP1) methanethiol oxidase (MTO) activity in mature enterocytes

“…Selenium, on the other hand, appears to bind to SELENBP1 mainly if applied at non-physiologically high doses [ 24 ]. Thus, SELENBP1 might provide an intracellular selenium buffer to cope with cytotoxic effects of selenite, as proposed for the C. elegans ortholog [ 25 , 26 ] rather than being dependent on selenium for its MTO activity. This idea is supported by a report showing SELENBP1 induction in human gastric cancer cells that were exposed to a cytotoxic dose of 30 μM selenite [ 27 ], whereas an adequate dose of 100 nM selenite did not result in elevated SELENBP1 levels in murine 3T3-L1 adipocytes [ 12 ].…”

“…This idea is supported by a report showing SELENBP1 induction in human gastric cancer cells that were exposed to a cytotoxic dose of 30 μM selenite [ 27 ], whereas an adequate dose of 100 nM selenite did not result in elevated SELENBP1 levels in murine 3T3-L1 adipocytes [ 12 ]. Similarly, the SELENBP1 ortholog Y37A1B.5/SEMO-1 in the nematode C. elegans was increased only in response to high doses of selenite [ 26 ].…”

Selenium-binding protein 1 (SELENBP1) is a copper-dependent thiol oxidase

“…Another insufficiently answered question relates to the physiological role of Se bound to SELENBP1 and its influence on the function of the protein. Human SELENBP1 as well as its orthologs in A. thaliana and C. elegans may provide a buffer against Se toxicity by binding excess selenite [ 15 , 29 , 30 ]. Moreover, physical interaction of SELENBP1 with the von Hippel-Lindau protein-interacting deubiquitinating enzyme 1 (VDU1) has been reported to be dependent on Se-binding of SELENBP1 [ 31 ].…”