Parathyroid hormone-dependent endocytosis of renal type IIc Na-Pi cotransporter
Parathyroid hormone-dependent endocytosis of renal type IIc Na-Pi cotransporter
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DOI：
10.1152/ajprenal.00100.2006
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发表时间：
2007-01-01
影响因子：
4.2
通讯作者：
Miyamoto, Ken-ichi
中科院分区：
文献类型：
--
作者：
Segawa, Hiroko;Yamanaka, Setsuko;Miyamoto, Ken-ichi
肾IIc型Na-P-i协同转运蛋白的甲状旁腺素依赖性内吞作用美国肾脏生理学杂志292：F395-F403，2007年。首次发表于2006年9月19日; doi：10.1152/ajprenal.00100.2006。遗传性低磷血症佝偻病伴高钙尿症是由肾IIc型Na-P-i协同转运蛋白基因突变引起的，这表明IIc型转运蛋白在肾磷酸盐处理中起着重要作用。本研究的目的是探讨甲状旁腺激素（PTH）对IIc型Na-P-i协同转运蛋白的调节。IIc型Na-P-i协同转运蛋白水平显着增加甲状腺甲状旁腺切除（TPTX）大鼠。PTH给药后4小时，顶膜组分中的IIc型转运蛋白水平显著降低，但在24小时恢复至基线水平。免疫组织化学分析表明，在TPTX动物近端肾小管细胞的顶膜和亚顶室中存在IIc型转运蛋白。PTH给药后，TPTX大鼠近端肾小管上皮细胞顶端和亚顶端IIc型转运蛋白的免疫反应信号强度降低。秋水仙素完全阻断了IIc型转运蛋白的内化。此外，亮抑酶肽阻止PTH介导的溶酶体中IIa型转运蛋白的降解，但对PTH介导的溶酶体IIc型转运蛋白的降解没有影响。在PTH处理的TPTX大鼠中，在给予PTH（1-34）（PKA和PKC激活剂）或PTH（3-34）（PKC激活剂）后发生IIc型转运蛋白的内化。因此，目前的研究表明，PTH是一个主要的激素调节剂的IIc型钠-磷-i协同转运蛋白在肾近端小管。
Parathyroid hormone-dependent endocytosis of renal type IIc Na-P-i cotransporter. Am J Physiol Renal Physiol 292: F395-F403, 2007. First published September 19, 2006; doi:10.1152/ajprenal.00100.2006.-Hereditary hypophosphatemic rickets with hypercalciuria results from mutations of the renal type IIc Na-P-i cotransporter gene, suggesting that the type IIc transporter plays a prominent role in renal phosphate handling. The goal of the present study was to investigate the regulation of the type IIc Na-P-i cotransporter by parathyroid hormone (PTH). Type IIc Na-P-i cotransporter levels were markedly increased in thyroparathyroidectomized (TPTX) rats. Four hours after administration of PTH, type IIc transporter protein levels were markedly decreased in the apical membrane fraction but recovered to baseline levels at 24 h. Immunohistochemical analyses demonstrated the presence of the type IIc transporter in the apical membrane and subapical compartments in the proximal tubular cells in TPTX animals. After administration of PTH, the intensity of immunoreactive signals in apical and subapical type IIc transporter decreased in the renal proximal tubular cells in TPTX rats. Colchicine completely blocked the internalization of the type IIc transporter. In addition, leupeptin prevented the PTH-mediated degradation of the type IIa transporter in lysosomes but had no effect on PTH-mediated degradation of the lysosomal type IIc transporter. In PTH-treated TPTX rats, the internalization of the type IIc transporter occurred after administration of PTH(1-34) (PKA and PKC activator) or PTH(3-34) (PKC activator). Thus the present study demonstrated that PTH is a major hormonal regulator of the type IIc Na-P-i cotransporter in renal proximal tubules.