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Rat Aquaporin-5 Is pH-Gated Induced by Phosphorylation and Is Implicated in Oxidative Stress

Rodrigues, Claudia; Mósca, Andreia Filipa; Martins, Ana Paula; Nobre, Tatiana; Prista, Catarina; Antunes, Fernando; Čipak Gašparović, Ana; Soveral, Graça (2016) Rat Aquaporin-5 Is pH-Gated Induced by Phosphorylation and Is Implicated in Oxidative Stress. International journal of molecular sciences, 17 (12). ISSN 1422-0067

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Aquaporin-5 (AQP5) is a membrane water channel widely distributed in human tissues that was found up-regulated in different tumors and considered implicated in carcinogenesis in different organs and systems. Despite its wide distribution pattern and physiological importance, AQP5 short-term regulation was not reported and mechanisms underlying its involvement in cancer are not well defined. In this work, we expressed rat AQP5 in yeast and investigated mechanisms of gating, as well as AQP5’s ability to facilitate H2O2 plasma membrane diffusion. We found that AQP5 can be gated by extracellular pH in a phosphorylation- dependent manner, with higher activity at physiological pH 7.4. Moreover, similar to other mammalian AQPs, AQP5 is able to increase extracellular H2O2 influx and to affect oxidative cell response with dual effects: whereas in acute oxidative stress conditions AQP5 induces an initial higher sensitivity, in chronic stress AQP5 expressing cells show improved cell survival and resistance. Our findings support the involvement of AQP5 in oxidative stress and suggest AQP5 modulation by phosphorylation as a novel tool for therapeutics.

Item Type: Article
Uncontrolled Keywords: aquaporin, yeast, permeability, phosphorylation, pH gating, reactive oxygen species, hydrogen peroxide, oxidative stress
Subjects: NATURAL SCIENCES > Biology
Divisions: Division of Molecular Medicine
Depositing User: Ana Čipak Gašparović
Date Deposited: 17 Jan 2018 10:55
DOI: 10.3390/ijms17122090

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