Specific binding proteins for selenium in rat tissues.

Abstract

The preventive and therapeutic potential of selenium (Se), a micronutrient, against cancer has been well documented in several test systems, but the mechanism of its action is not known. The possibility that Se might function in a manner similar to steroid hormones and retinoids through mediation of cellular receptors 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 administration of Na2[75Se]O3 to rats resulted in its uptake by the tissues with concomitant appearance of [75Se]SeBP complex. The protein binds sodium selenite with moderately high affinity; the apparent dissociation constant was determined by Scatchard analysis to be 1.1 X 10(-7) M. SeBP focused at pH 5.3 upon isoelectric focusing in ampholines of pH 3-10. Competitive binding affinity studies with unlabeled test compounds revealed that selenium dioxide and selenocystine showed high binding affinity (90-95%) for the selenite-binding site on SeBP. Sodium selenate, elemental Se powder, and selenomethionine, however, showed poor competition with sodium selenite. Biological activity of the above selenocompounds, as expressed by others, correlate with their binding affinities for SeBP. Sodium sulfite showed 35% 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 less than 10% inhibition of binding. Interaction of Se with SeBP is completely blocked by thiol inhibitors. Plasma transport of Na2[75Se]O3 is mediated by a protein with a mol. wt of 68,000, which is presently identified, by immunoprecipitation studies as well as by Affi-Gel Blue column chromatographic experiments, as serum albumin. The results suggest that the plasma transport of Se is facilitated by albumin, and that the intracellular transport of Se for its biological functions is accomplished by SeBP.