In:
Nephron, S. Karger AG, Vol. 133, No. 4 ( 2016), p. 287-295
Abstract:
〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 WNK kinase is a serine/threonine kinase that plays an important role in normal blood pressure homeostasis. WNK3 was previously found to enhance the activity of sodium chloride cotransporter (NCC) in 〈 i 〉 Xenopus 〈 /i 〉 oocyte. However, the mechanism through which it works remains unclear. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 Using overexpression and siRNA knock-down techniques, the effects of WNK3 on NCC in both Cos-7 and mouse distal convoluted cells were analyzed by Western blot. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 We found that WNK3 significantly increased NCC protein expression in a dose-dependent manner. NCC protein expression in Cos-7 cells was markedly decreased after 2 h treatment with protease inhibitor, cycloheximide (CHX) in the NCC alone group, but was significantly decreased after 8 h treatment of CHX in the WNK3 + NCC group. WNK3 significantly increased NCC protein expression in both NCC alone and WNK3 + NCC groups regardless the overnight treatments of bafilomycin A1, a proton pump inhibitor, suggesting that WNK3-mediated increased NCC expression is not dependent on the lysosomal pathway. We further found that WNK3 group had a quicker NCC recovery than the control group using CHX pulse assay, suggesting that WNK3 increases NCC protein synthesis. WNK3 enhanced NCC protein level while reducing ERK 1/2 phosphorylation. In addition, knock-down of ERK 1/2 expression reversed WNK3-mediated increase of NCC expression. 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 These results suggest that WNK3 enhances NCC protein expression by increasing NCC synthesis via an ERK 1/2-dependent signaling pathway.
Type of Medium:
Online Resource
ISSN:
1660-8151
,
2235-3186
Language:
English
Publisher:
S. Karger AG
Publication Date:
2016
detail.hit.zdb_id:
2810853-X
Permalink