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Open AccessArticle

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

1
Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisboa, Portugal
2
Department of Biochemistry and Human Biology, Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisboa, Portugal
3
Linking Landscape, Environment, Agriculture and Food, Instituto Superior de Agronomia, Universidade de Lisboa, 1349-017 Lisboa, Portugal
4
Centro de Química e Bioquímica e Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade de Lisboa, 1749-016 Lisboa, Portugal
5
Rudjer Boskovic Institute, HR 10000 Zagreb, Croatia
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Kenichi Ishibashi
Int. J. Mol. Sci. 2016, 17(12), 2090; https://doi.org/10.3390/ijms17122090
Received: 28 September 2016 / Revised: 25 November 2016 / Accepted: 6 December 2016 / Published: 13 December 2016
(This article belongs to the Special Issue Aquaporin)
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. View Full-Text
Keywords: aquaporin; yeast; permeability; phosphorylation; pH gating; reactive oxygen species; hydrogen peroxide; oxidative stress aquaporin; yeast; permeability; phosphorylation; pH gating; reactive oxygen species; hydrogen peroxide; oxidative stress
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MDPI and ACS Style

Rodrigues, C.; Mósca, A.F.; Martins, A.P.; Nobre, T.; Prista, C.; Antunes, F.; Cipak Gasparovic, A.; Soveral, G. Rat Aquaporin-5 Is pH-Gated Induced by Phosphorylation and Is Implicated in Oxidative Stress. Int. J. Mol. Sci. 2016, 17, 2090.

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