Effects of sodium butyrate on 1,25-dihydroxyvitamin D 3 receptor activity in primary chick kidney cells

Abstract

The genomic effects of the steroid hormone 1,25-dihydroxyvitamin D 3 (1,25(OH) 2D 3) are mediated by high affinity nuclear associated specific receptors that belong to the superfamily of ligand induced transcription factors. The carboxylic acid, sodium butyrate — a potent inhibitor of histone deacetylase — is known to modulate gene expression in a variety of systems. Specific binding of 1,25(OH) 2D 3 to its receptor was examined in primary chick kidney cells, the chick macrophage cell line HD-11, and other mammalian cell lines such as ROS 17 2.8 , HT-29 and CV-1 cells, that were all cultured in the presence or absence of 1 mM sodium butyrate. Treatment with n-butyrate resulted in significant (4.0–4.5-fold) increases in 1,25(OH) 2D 3 receptor binding without changing binding affinity only in the primary cultures of chick renal epithelial cells and the chick macrophage cell line but not in the other heterologous receptor-positive cell lines. The maximum increase in receptor binding was evident at 1 mM butyrate concentration. This effect reached a maximum at 15 h treatment, beyond which there was slow attenuation in increased binding until 24 h. The butyrate induced increases in receptor activity was associated with increases in the 1,25(OH) 2D 3-mediated induction of calbindin-D 28K protein only in primary chick kidney cultures but not in the macrophage cell line (HD-11). Similarly, calbindin-D 28K promoter activity was enhanced only in butyrate-treated primary chick kidney cultures, transfected with chimeric plasmids containing the 5' flanking sequence of the calbindin-D 28K promoter fused to the chloramphenicol acetyl transferase (CAT) reporter gene but not in HD-11 cells. These data suggest that sodium butyrate influences 1,25(OH) 2D 3 receptor activity in a cell specific manner and this increase in receptor activity in the primary chick kidney cells parallels with the increased expression of calbindin-D 28K protein.