Specific binding proteins for selenium in rat tissues

The preventive and therapeutic potential of selenium (Se), amicronutrient, against cancer has been well documented in severaltest systems, but the mechanism of its action is not known.The possibility that Se might function in a manner similar tosteroid hormones and retinoids through mediation of cellularreceptors was examined. A specific 2S cellular binding protein(SeBP) for Na₂[⁷⁵Se]O₃ was detected in rat tissue extracts.Liver and intestine exhibited highest levels of SeBP, and heart,uterus and spleen had the lowest levels. Oral administrationof Na₂[⁷⁵Se]O₃ to rats resulted in its uptake by the tissueswith concomitant appearance of [⁷⁵Se]SeBP complex. The proteinbinds sodium selenite with moderately high affinity; the apparentdissociation constant was determined by Scatchard analysis tobe 1.1x10^–7 M. SeBP focused at pH 5.3 upon isoelectricfocusing in ampholines of pH 3–10. Competitive bindingaffinity studies with unlabeled test compounds revealed thatselenium dioxide and selenocystine showed high binding affinity(90–95%) for the selenite-binding site on SeBP. Sodiumselenate, elemental Se powder, and selenomethionine, however,showed poor competition with sodium selenite. Biological activityof the above selenocompounds, as expressed by others, correlatewith their binding affinities for SeBP. Sodium sulfite showed35% inhibition of Na₂[⁷⁵Se]O₃ binding, but sulfate showed none.Two ultimate carcinogens, N-methyl-N-nitrosourea and N-methyl-N'-nitro-N-nitrosoguanidine,and two retinoids, retinol and retinoic acid, showed <10%inhibition of binding. Interaction of Se with SeBP is completelyblocked by thiol inhibitors. Plasma transport of Na₂[⁷⁵Se]O₃is mediated by a protein with a mol. wt of 68000, which is presentlyidentified, by immunoprecipitation studies as well as by Affi-GelBlue column chromatographic experiments, as serum albumin. Theresults suggest that the plasma transport of Se is facilitatedby albumin, and that the intracellular transport of Se for itsbiological functions is accomplished by SeBP.