Source
Nephrology Research Unit, Mayo Clinic and Foundation, 200 First Street SW, Rochester, Minnesota, 55905, USA.
Abstract
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.
Copyright 2000 Academic Press.