title: Stress Regulates Aquaporin-8 Permeability to Impact Cell Growth and Survival.
abstract: Aquaporin-8 (AQP8) allows the bidirectional transport of water and hydrogen peroxide across biological membranes. Depending on its concentration, H2O2 exerts opposite roles, amplifying growth factor signaling in physiological conditions, but causing severe cell damage when in excess. Thus, H2O2 permeability is likely to be tightly controlled in living cells.
  
  
  
  In this study, we investigated whether and how the transport of H2O2 through plasma membrane AQP8 is regulated, particularly during cell stress.
  
  
  
  We show that diverse cellular stress conditions, including heat, hypoxia, and ER stress, reversibly inhibit the permeability of AQP8 to H2O2 and water. Preventing the accumulation of intracellular reactive oxygen species (ROS) during stress counteracts AQP8 blockade. Once inhibition is established, AQP8-dependent transport can be rescued by reducing agents. Neither H2O2 nor water transport is impaired in stressed cells expressing a mutant AQP8, in which cysteine 53 had been replaced by serine. Cells expressing this mutant are more resistant to stress-, drug-, and radiation-induced growth arrest and death.
  
  
  
  The control of AQP8-mediated H2O2 transport provides a novel mechanism to regulate cell signaling and survival during stress. Antioxid. Redox Signal. 24, 1031-1044.
authors.affiliation: 1 Protein Transport and Secretion Unit, Division of Genetics and Cell Biology, IRCCS Ospedale San Raffaele/Università Vita-Salute San Raffaele , Milan, Italy .
authors.forename: Iria
authors.initials: I
authors.lastname: Medraño-Fernandez
authors.affiliation: 1 Protein Transport and Secretion Unit, Division of Genetics and Cell Biology, IRCCS Ospedale San Raffaele/Università Vita-Salute San Raffaele , Milan, Italy .
authors.forename: Stefano
authors.initials: S
authors.lastname: Bestetti
authors.affiliation: 1 Protein Transport and Secretion Unit, Division of Genetics and Cell Biology, IRCCS Ospedale San Raffaele/Università Vita-Salute San Raffaele , Milan, Italy .
authors.forename: Milena
authors.initials: M
authors.lastname: Bertolotti
authors.affiliation: 2 Metalloid Transport Group, Leibniz Institute of Plant Genetics and Crop Plant Research , Gatersleben, Germany .
authors.forename: Gerd P
authors.initials: GP
authors.lastname: Bienert
authors.affiliation: 3 Department of Molecular Medicine, University of Pavia , Pavia, Italy .
authors.forename: Cinzia
authors.initials: C
authors.lastname: Bottino
authors.affiliation: 3 Department of Molecular Medicine, University of Pavia , Pavia, Italy .
authors.forename: Umberto
authors.initials: U
authors.lastname: Laforenza
authors.affiliation: 4 Cell Biology Unit, IRCCS AOU San Martino-IST , Genoa, Italy .
authors.forename: Anna
authors.initials: A
authors.lastname: Rubartelli
authors.affiliation: 1 Protein Transport and Secretion Unit, Division of Genetics and Cell Biology, IRCCS Ospedale San Raffaele/Università Vita-Salute San Raffaele , Milan, Italy .
authors.forename: Roberto
authors.initials: R
authors.lastname: Sitia
mesh_terms: D020346:Aquaporins / Q000235:genetics / Q000378:metabolism*; D001692:Biological Transport; D002463:Cell Membrane Permeability; D049109:Cell Proliferation; D002470:Cell Survival; D015870:Gene Expression; D006367:HeLa Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D012441:Saccharomyces cerevisiae; D014867:Water / Q000378:metabolism
chemical_list: D020346:Aquaporins; C108330:aquaporin 8; D014867:Water; D006861:Hydrogen Peroxide