AJP - Cell Physiology, Vol 262, Issue 1 C235-C242, Copyright © 1992 by American Physiological Society
1 alpha,25-(OH)2 vitamin D3 enhances expression of the genes encoding Ca(2+)-binding proteins MRP-8 and MRP-14
A. Sellmayer, S. M. Krane, A. J. Ouellette and J. V. Bonventre
Department of Medicine, Harvard Medical School, Boston, Massachusetts.
Two closely related Ca(2+)-binding proteins, migration inhibitory
factor-related protein (MRP)-8 and MRP-14, are synthesized under specific
conditions of myeloid cell differentiation. Because 1
alpha,25-dihydroxyvitamin D3 [1,25-(OH)2D3] induces myeloid cell
differentiation and expression of other S-100 class calcium-binding
proteins, we examined the effects of 1,25-(OH)2D3 on MRP mRNA levels in
human U-937 histiocytic lymphoma cells. 1,25-(OH)2D3 increased MRP-8 and
MRP-14 mRNA levels in a time- and dose-dependent manner. MRP mRNA levels
were maximal at 24 h and remained elevated for at least 96 h after exposure
of the cells to 1,25-(OH)2D3. MRP-8 mRNA accumulation required 100- to
1,000-fold higher concentrations of 25-(OH)D3, which binds to the
1,25-(OH)2D3 intracellular receptor with 100- to 1,000-fold lower affinity.
Other differentiating agents, dimethyl sulfoxide, retinoic acid, and
dexamethasone, also increased levels of MRP-8 and MRP-14 mRNA. Phorbol
myristate acetate enhanced MRP-14 mRNA levels to a greater extent than
MRP-8 mRNA levels, suggesting differential regulation of MRP gene
expression by protein kinase C. The 1,25-(OH)2D3-induced relative increase
in MRP mRNA levels was not changed by a 1,000-fold reduction in
extracellular [Ca2+]. Thus 1,25-(OH)2D3 is potentially a physiological
modulator of MRP gene expression. Expression of the MRP-8 and MRP-14 genes
may be important for differentiation of myeloid cells.
