TPA decreases 1,25(OH)2D3 binding and calbindin D-28K in renal (MDBK) cells.
The effect of the phorbol ester TPA (12-O-tetradecanoylphorbol 13-acetate) on vitamin D receptors (VDRs) was studied in MDBK cells, a normal bovine renal epithelial cell line. 24 h treatment of MDBK cells with TPA resulted in down-regulation of VDR number, with no change in the binding affinity for 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) or approximate molecular weight determined by fast protein liquid chromatography (FPLC). TPA treatment also reduced the level of calbindin D-28K, a vitamin D-dependent renal protein. 4 alpha-Phorbol 12,13-didecanoate (4 alpha-PDD), an inactive phorbol ester, did not affect either 1,25(OH)2D3 binding or calbindin D-28K levels. TPA elicited a significant decrease in membrane-associated protein kinase C (PKC) activity which coincided with the reduction in VDR number and calbindin D-28K. These data support a link between TPA, PKC activity and vitamin D actions in kidney.
Simboli-Campbell
M
M
Department of Biochemistry, University of Ottawa, Ontario, Canada.
Gagnon
A M
AM
Franks
D J
DJ
Welsh
J
J
D000818:Animals; D001665:Binding Sites; D064026:Calbindins; D002117:Calcitriol / Q000378:metabolism*; D002417:Cattle; D002460:Cell Line; D004247:DNA / Q000096:biosynthesis; D015536:Down-Regulation; D004848:Epithelium; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid / Q000378:metabolism*; D064030:S100 Calcium Binding Protein G / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D064026:Calbindins; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid; D064030:S100 Calcium Binding Protein G; D004247:DNA; D011493:Protein Kinase C; D002117:Calcitriol; D013755:Tetradecanoylphorbol Acetate