DEXAMETHASONE MODULATES RAT RENAL BRUSH-BORDER MEMBRANE PHOSPHATE TRANSPORTER MESSENGER-RNA AND PROTEIN ABUNDANCE AND GLYCOSPHINGOLIPID COMPOSITION
DEXAMETHASONE MODULATES RAT RENAL BRUSH-BORDER MEMBRANE PHOSPHATE TRANSPORTER MESSENGER-RNA AND PROTEIN ABUNDANCE AND GLYCOSPHINGOLIPID COMPOSITION
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DOI：
10.1172/jci118022
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发表时间：
1995-07-01
影响因子：
15.9
通讯作者：
WILSON, P
中科院分区：
文献类型：
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作者：
LEVI, M;SHAYMAN, JA;WILSON, P
糖皮质激素是肾脏磷酸盐转运的重要调节剂。本研究探讨了大鼠肾刷状缘膜（BBM）钠梯度依赖性磷酸盐转运（Na-Pi cotransporter）mRNA和蛋白丰度的改变在地塞米松诱导的钠-Pi共转运抑制中的作用。地塞米松给药4d后，Na-Pi共转运的最大速度增加了1.5倍（1785 ± 119 vs 2759 ± 375 pmol/5 s/mg BBM蛋白，P < 0.01），但Na-Pi mRNA和蛋白的丰度降低了2.5倍。BBM葡糖神经酰胺含量也增加了1.7倍（528+/-63vs.312 +/-41ng/mg BBM蛋白，P < 0.02）。为了确定葡萄糖神经酰胺含量本身的改变是否在钠-磷共转运的减少中发挥功能性作用，用葡萄糖神经酰胺合酶抑制剂D-苏型-1-苯基-2-癸酰基-氨基-3-吗啉代-1-丙醇（PGEX）处理对照大鼠。结果BBM葡萄糖神经酰胺含量降低1.5倍，（199+/-19vs，312 +/-41ng/mgBBM蛋白对照组，P < 0.02）与Na-Pi共转运活性增加1.4倍相关（1422+/-73 pmol/5 s/mg BBM蛋白对比对照中的1048+/-85 pmol/5 s/mg BBM蛋白，P < 0.01），并且BBM Na-Pi蛋白丰度增加1.5倍。因此，地塞米松诱导的钠-磷共转运抑制与BBM钠-磷共转运蛋白丰度的降低和葡萄糖神经酰胺的增加有关。由于BBM葡糖神经酰胺含量本身的主要变化直接和选择性地调节BBM钠-Pi共转运活性和钠-Pi蛋白丰度，我们建议BEM葡糖神经酰胺含量的增加在介导地塞米松对钠-Pi共转运活性的抑制作用中起重要作用。
Glucocorticoids are important regulators of renal phosphate transport. This study investigates the role of alterations in renal brush border membrane (BBM) sodium gradient-dependent phosphate transport (Na-Pi cotransporter) mRNA and protein abundance in the dexamethasone induced inhibition of Na-Pi cotransport in the rat. Dexamethasone administration for 4 d caused a 1.5-fold increase in the V-max of Na-Pi cotransport (1785+/-119 vs, 2759+/-375 pmol/5 s per mg BBM protein in control, P < 0.01), which was paralleled by a 2.5-fold decrease in the abundance of Na-Pi mRNA and Na-Pi protein. There was also a 1.7-fold increase in BBM glucosylceramide content (528+/-63 vs. 312+/-41 ng/mg BBM protein in control, P < 0.02). To determine whether the alteration in glucosylceramide content per se played a functional role in the decrease in Na-Pi cotransport, control rats were treated with the glucosylceramide synthase inhibitor, D-threo-1-phenyl-2-decanoyl-amino-3-morpholino-1 propanol (PDMP). The resultant 1.5-fold decrease in BBM glucosylceramide content (199+/-19 vs, 312+/-41 ng/mg BBM protein in control, P < 0.02) was associated with a 1.4-fold increase in Na-Pi cotransport activity (1422+/-73 vs. 1048+/-85 pmol/5 s per mg BBM protein in control, P < 0.01), and a 1.5-fold increase in BBM Na-Pi protein abundance. Thus, dexamethasone-induced inhibition of Na-Pi cotransport is associated with a decrease in BBM Na-Pi cotransporter abundance, and an increase in glucosylceramide. Since primary alteration in BBM glucosylceramide content per se directly and selectively modulates BBM Na-Pi cotransport activity and Na-Pi protein abundance, we propose that the increase in BEM glucosylceramide content plays an important role in mediating the inhibitory effect of dexamethasone on Na-Pi cotransport activity.