Expression and phosphorylation of the Na+-Cl- cotransporter NCC in vivo is regulated by dietary salt, potassium, and SGK1
Expression and phosphorylation of the Na+-Cl- cotransporter NCC in vivo is regulated by dietary salt, potassium, and SGK1
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DOI：
10.1152/ajprenal.00030.2009
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发表时间：
2009-09-01
影响因子：
4.2
通讯作者：
Uchida, Shinichi
中科院分区：
文献类型：
--
作者：
Vallon, Volker;Schroth, Jana;Uchida, Shinichi
[10]杨文，杨文.体内Na+-Cl-协同转运蛋白NCC的表达和磷酸化受膳食盐、钾和SGK 1的调节。美国生理学杂志肾脏生理学297：F704-F712，2009年。首次发表于2009年7月1日; doi：10.1152/ajprenal.00030.2009。Na-Cl协同转运蛋白NCC在远曲小管中表达，通过磷酸化激活，并与肾脏NaCl和K+稳态有关。血清和糖皮质激素诱导激酶1（SGK 1）至少部分地通过刺激醛固酮敏感性Na+/K+交换下游段的上皮Na+通道和Na+-K+-ATP酶来促进肾脏的NaCl潴留和K+排泄。在这项研究中，我们在野生型小鼠（WT）中证实，饮食NaCl限制分别增加肾脏NCC表达及其在Thr 53，Thr（58）和Ser（71）的磷酸化。然而，这种反应在缺乏SGK 1（Sgk 1（-/-））的小鼠中减弱，这可能导致这些小鼠中NaCl潴留受损。与高K+饮食相比，WT中总肾脏NCC表达和Thr 53、Thr 58和Ser 71的磷酸化在低K+饮食下更大。这一发现与NCC调节Na+递送至Na+/K+交换的下游区段，从而调节K+排泄的调节一致。在Sgk 1（-/-）小鼠中，肾脏总NCC和磷酸化NCC表达的饮食K+依赖性变化未减弱。事实上，高钾饮食诱导的NCC抑制在Sgk 1（-/-）小鼠中增强。在Sgk 1（-/-）小鼠中由高K+饮食诱导的高钾血症可能增强了NCC抑制，从而增加Na+递送并促进受损Na+/K+交换下游区段中的K+排泄。总之，NaCl和K+摄入量的变化改变了NCC的表达和磷酸化，这一观察结果与NCC在NaCl和K+稳态中的作用一致。这两个演习解离血浆醛固酮水平从NCC的表达和磷酸化，涉及额外的监管机构。饮食NaCl限制对NCC表达和磷酸化的调节似乎涉及SGK 1。
Vallon V, Schroth J, Lang F, Kuhl D, Uchida S. Expression and phosphorylation of the Na+-Cl- cotransporter NCC in vivo is regulated by dietary salt, potassium, and SGK1. Am J Physiol Renal Physiol 297: F704-F712, 2009. First published July 1, 2009; doi:10.1152/ajprenal.00030.2009.- The Na-Cl cotransporter NCC is expressed in the distal convoluted tubule, activated by phosphorylation, and has been implicated in renal NaCl and K+ homeostasis. The serum and glucocorticoid inducible kinase 1 (SGK1) contributes to renal NaCl retention and K+ excretion, at least in part, by stimulating the epithelial Na+ channel and Na+-K+-ATPase in the downstream segments of aldosterone-sensitive Na+/K+ exchange. In this study we confirmed in wild-type mice (WT) that dietary NaCl restriction increases renal NCC expression and its phosphorylation at Thr53, Thr(58), and Ser(71), respectively. This response, however, was attenuated in mice lacking SGK1 (Sgk1(-/-)),which may contribute to impaired NaCl retention in those mice. Total renal NCC expression and phosphorylation at Thr53, Thr58, and Ser71 in WT were greater under low- compared with high-K+ diet. This finding is consistent with a regulation of NCC to modulate Na+ delivery to downstream segments of Na+/K+ exchange, thereby modulating K+ excretion. Dietary K+-dependent variation in renal expression of total NCC and phosphorylated NCC were not attenuated in Sgk1(-/-) mice. In fact, high-K+ diet-induced NCC suppression was enhanced in Sgk1(-/-) mice. The hyperkalemia induced in Sgk1(-/-) mice by a high- K+ diet may have augmented NCC suppression, thereby increasing Na+ delivery and facilitating K+ excretion in downstream segments of impaired Na+/K+ exchange. In summary, changes in NaCl and K+ intake altered NCC expression and phosphorylation, an observation consistent with a role of NCC in NaCl and K+ homeostasis. The two maneuvers dissociated plasma aldosterone levels from NCC expression and phosphorylation, implicating additional regulators. Regulation of NCC expression and phosphorylation by dietary NaCl restriction appears to involve SGK1.