Synergistical effect of 20-HETE and high salt on NKCC2 protein and blood pressure via ubiquitin–proteasome pathway
Synergistical effect of 20-HETE and high salt on NKCC2 protein and blood pressure via ubiquitin–proteasome pathway
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DOI：
10.1007/s00439-012-1238-3
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发表时间：
2013-02
期刊：
影响因子：
5.3
通讯作者：
Jingjing Wu;Xiaoliang Liu;Guangrui Lai;Xiang-Hong Yang;Luzeng Wang;Yanyan Zhao
中科院分区：
文献类型：
--
作者：
Jingjing Wu;Xiaoliang Liu;Guangrui Lai;Xiang-Hong Yang;Luzeng Wang;Yanyan Zhao
We previously generated a cytochrome P450 4F2 (CYP4F2) transgenic mouse model and demonstrated that overexpressed CYP4F2 and overproduced 20-HETE in the kidneys contribute to the increase of blood pressure in theCYP4F2transgenic mice with normal salt intake. We currently expect to elucidate a potential mechanism of salt-related hypertension whereby diverse levels of 20-HETE interact with dietary salt on Na+-K+-2Cl−cotransporter, isoform 2 (NKCC2) in the kidneys of the transgenic and wild-type mice with high salt intake. High salt intake reduced about 85 % abundance of renal NKCC2 protein in the transgenic mice and about 24 % in the wild-type mice by Western blot. Furthermore, we first found that NKCC2 was ubiquitinated and interacted with Nedd4-2 by immunoprecipitation in the transgenic mice with high salt intake. In addition, inhibition of 20-HETE synthesis or proteasome activity reversed the reduction of NKCC2 expression induced by 20-HETE and high salt intake. These results suggest that 20-HETE and high salt intake synergistically decrease the expression of NKCC2 protein via Nedd4-2-mediated ubiquitin–proteasome pathway, and thereby modulate natriuresis and blood pressure. We propose that diverse levels of 20-HETE have diverse effects on blood pressure in different salt concentrations.
