WNK3激酶对钠氯协同转运子的调节作用及机制研究

项目名称： WNK3激酶对钠氯协同转运子的调节作用及机制研究

项目编号： No.81200513

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学二处

项目作者： 王德选

作者单位： 温州医科大学

项目金额： 23万元

中文摘要： 水钠潴留为高血压发病机制的核心环节之一。研究表明WNK 激酶(With No Lysine Kinase)和肾脏钠氯转运子（NCC）对调节血压和维持电解质平衡起重要作用。已知WNK 激酶家族成员之一WNK3能促进爪蛙卵母细胞NCC 的活性，本项目拟①应用免疫荧光等途径探索WNK3和NCC在哺乳动物肾脏细胞内的分布；②通过药物干预细胞蛋白合成及溶酶体降解等途径，采用western-blot、细胞表面生物素标记等方法了解两者的相互作用，观察WNK3对NCC蛋白合成、降解、细胞内吞的影响机制；③将不同致病体的WNK3转入细胞，观察WNK3酶活性区域对NCC的作用。旨在通过探讨WNK3 激酶对NCC 的调控机制，为阐明高血压的部分发病机理及开发新的降压药作用靶点提供分子生物学依据。

中文关键词： WNK3激酶；钠氯协调转运体；高血压；凋亡；

英文摘要： Water-sodium retention is one of the core aspects of the pathogenesis of hypertension. And the latest researches have shown that WNK (With No Lysine Kinase) and NCC(sodium chloride cotransporter) play an important role in the regulation of blood pressure and maintenance of electrolyte balance. Since WNK3, an important member of the WNK family, was proved to increase the activity of NCC in oocytes of Xenopuslaevis, we hypothesize a similar change in renal cells of mammal. The plan is as follows.① To observe the distribution of WNK3 and NCC in renal cells of mammal by immunofluorescence. ② To understand the interaction between WNK3 and NCC through drug interference with the synthesis of cell proteins and the lysosomal pathway by means of western blotting and cell surface biotin labelling,mainly focusing on the possible mechanisms that WNK3 works upon synthesis, degradation and endocytosis of NCC protein. ③ To find out the effect of WNK3 active region on NCC by the transfection of WNK3 from different pathotypes. By tracing the action mechanism of WNK3 upon NCC, we aim to elucidate etiopathogenesis of hypertension and throw fresh light on the exploitation of a new action target for hypertensive drugs.

英文关键词： WNK3；NCC；hypertension；apoptosis；