Cu1+, but not Cu2+ is capable of inhibition of AQP4 permeability in an in vitro CHO cell based model

Arno Vandebroek, Masato Yasui

研究成果: Article査読

抄録

Aquaporin 4 (AQP4) is an important water channel in the central nervous system which is implicated in several neurological disorders. Due to its significance, the identification of molecules which are able to modulate its activity is quite important for potential therapeutic applications. Here we used a novel screening method involving CHO cell lines which stably express AQP4 to test for potential molecules of interest. Using this method we identified a metal ion, Cu1+, which is able to inhibit AQP4 activity in a cell model, an interaction which has not been previously described. This inhibition was effective at concentrations greater than 500 nM in the CHO cell model, and was confirmed in a proteoliposome based model. Furthermore, the binding sites for Cu1+ inhibition of AQP4 are identified as cysteine 178 and cysteine 253 on the intracellular domain of the protein via the synthesis of AQP4 containing point mutations to remove these cysteines. These results suggest that Cu1+ is able to access intracellular binding sites and inhibit AQP4 in a cell based model.

本文言語English
論文番号101132
ジャーナルBiochemistry and Biophysics Reports
28
DOI
出版ステータスPublished - 2021 12月

ASJC Scopus subject areas

  • 生物理学
  • 生化学

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