Zinc increases the activity of vitamin D-dependent promoters in osteoblasts.
Zinc modulates the structure and binding of the DNA binding domain of the 1alpha,25-dihydroxyvitamin D(3) receptor to specific vitamin D response element DNA (Nature Biotechnology 16, 262-266, 1998). To determine whether zinc alters 1alpha,25-dihydroxyvitamin D(3)-regulated genes in cells, we permanently transfected rat osteoblasts with two vitamin D-dependent promoter-reporter systems and examined their responses to 1alpha,25-dihydroxyvitamin D(3) in the presence of increasing amounts of extracellular zinc. When extracellular zinc concentrations were increased in the presence of 1alpha,25-dihydroxyvitamin D(3), there was an increase in the activity of 1alpha,25-dihydroxyvitamin D(3)-dependent promoters with increasing concentrations of zinc. The effect was specific for zinc since metals such as copper failed to increase the activity of 1alpha,25-dihydroxyvitamin D(3)-dependent promoters. The concentration of the vitamin D receptor within the cell and the affinity of 1alpha,25-dihydroxyvitamin D(3) for its receptor remained unchanged with added zinc. Our results show that zinc increases the activity of 1alpha,25-dihydroxyvitamin D(3)-dependent promoters in osteoblasts.
Lutz
W
W
Nephrology Research Unit, Mayo Clinic and Foundation, 200 First Street SW, Rochester, Minnesota, 55905, USA.
Burritt
M F
MF
Nixon
D E
DE
Kao
P C
PC
Kumar
R
R
D000818:Animals; D015153:Blotting, Western; D003300:Copper / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D008156:Luciferases / Q000378:metabolism; D010006:Osteoblasts / Q000378:metabolism*; D053495:Osteopontin; D010957:Plasmids; D011401:Promoter Regions, Genetic; D051381:Rats; D018167:Receptors, Calcitriol / Q000378:metabolism; D012795:Sialoglycoproteins / Q000235:genetics; D013250:Steroid Hydroxylases / Q000235:genetics; D014162:Transfection; D014407:Tumor Cells, Cultured; D014807:Vitamin D / Q000031:analogs & derivatives / Q000235:genetics* / Q000378:metabolism; D065668:Vitamin D3 24-Hydroxylase; D015032:Zinc / Q000494:pharmacology / Q000502:physiology*
D018167:Receptors, Calcitriol; D012795:Sialoglycoproteins; C506897:Spp1 protein, rat; D053495:Osteopontin; D014807:Vitamin D; D003300:Copper; D003577:Cytochrome P-450 Enzyme System; D008156:Luciferases; D013250:Steroid Hydroxylases; D065668:Vitamin D3 24-Hydroxylase; D015032:Zinc