组织型纤溶酶原激活剂（TPA）可降低肾（MDBK）细胞中1,25(OH)2D3的结合及钙结合蛋白D-28K的水平。

TPA decreases 1,25(OH)2D3 binding and calbindin D-28K in renal (MDBK) cells.

作者信息

Simboli-Campbell M, Gagnon A M, Franks D J, Welsh J

机构信息

Department of Biochemistry, University of Ottawa, Ontario, Canada.

出版信息

Mol Cell Endocrinol. 1992 Feb;83(2-3):143-51. doi: 10.1016/0303-7207(92)90155-y.

DOI:10.1016/0303-7207(92)90155-y

PMID:1312489

Abstract

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.

摘要

在正常牛肾上皮细胞系MDBK细胞中研究了佛波酯TPA（12 - O - 十四烷酰佛波醇13 - 乙酸酯）对维生素D受体（VDR）的影响。用TPA处理MDBK细胞24小时导致VDR数量下调，对1,25 - 二羟基维生素D3（1,25(OH)2D3）的结合亲和力以及通过快速蛋白质液相色谱（FPLC）测定的近似分子量均无变化。TPA处理还降低了钙结合蛋白D - 28K的水平，钙结合蛋白D - 28K是一种维生素D依赖的肾蛋白。4α - 佛波醇12,13 - 二癸酸酯（4α - PDD），一种无活性的佛波酯，对1,25(OH)2D3结合或钙结合蛋白D - 28K水平均无影响。TPA引起膜相关蛋白激酶C（PKC）活性显著降低，这与VDR数量和钙结合蛋白D - 28K的减少相一致。这些数据支持了TPA、PKC活性与肾脏中维生素D作用之间的联系。