title: Rat Aquaporin-5 Is pH-Gated Induced by Phosphorylation and Is Implicated in Oxidative Stress.
abstract: 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.
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisboa, Portugal. crodrigues@ff.ulisboa.pt.|Department of Biochemistry and Human Biology, Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisboa, Portugal. crodrigues@ff.ulisboa.pt.
authors.forename: Claudia
authors.initials: C
authors.lastname: Rodrigues
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisboa, Portugal. andreiafbm@ff.ulisboa.pt.|Department of Biochemistry and Human Biology, Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisboa, Portugal. andreiafbm@ff.ulisboa.pt.
authors.forename: Andreia Filipa
authors.initials: AF
authors.lastname: Mósca
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisboa, Portugal. martinsap@ff.ulisboa.pt.|Department of Biochemistry and Human Biology, Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisboa, Portugal. martinsap@ff.ulisboa.pt.
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Martins
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisboa, Portugal. t.nobre@campus.ul.pt.|Department of Biochemistry and Human Biology, Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisboa, Portugal. t.nobre@campus.ul.pt.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Nobre
authors.affiliation: Linking Landscape, Environment, Agriculture and Food, Instituto Superior de Agronomia, Universidade de Lisboa, 1349-017 Lisboa, Portugal. cprista@isa.ulisboa.pt.
authors.forename: Catarina
authors.initials: C
authors.lastname: Prista
authors.affiliation: Centro de Química e Bioquímica e Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade de Lisboa, 1749-016 Lisboa, Portugal. fantunes@fc.ul.pt.
authors.forename: Fernando
authors.initials: F
authors.lastname: Antunes
authors.affiliation: Rudjer Boskovic Institute, HR 10000 Zagreb, Croatia. Ana.Cipak.Gasparovic@irb.hr.
authors.forename: Ana
authors.initials: A
authors.lastname: Cipak Gasparovic
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisboa, Portugal. gsoveral@ff.ulisboa.pt.|Department of Biochemistry and Human Biology, Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisboa, Portugal. gsoveral@ff.ulisboa.pt.
authors.forename: Graça
authors.initials: G
authors.lastname: Soveral
mesh_terms: D000818:Animals; D051402:Aquaporin 5 / Q000737:chemistry / Q000378:metabolism*; D002463:Cell Membrane Permeability / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000633:toxicity; D006863:Hydrogen-Ion Concentration; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism; D014867:Water / Q000378:metabolism
chemical_list: D051402:Aquaporin 5; D014867:Water; D006861:Hydrogen Peroxide; D005947:Glucose
keywords: aquaporin; hydrogen peroxide; oxidative stress; pH gating; permeability; phosphorylation; reactive oxygen species; yeast