Iria Medraño-Fernandez1, Stefano Bestetti1, Milena Bertolotti1, Gerd P Bienert2, Cinzia Bottino3, Umberto Laforenza3, Anna Rubartelli4, Roberto Sitia1. 1. 1 Protein Transport and Secretion Unit, Division of Genetics and Cell Biology, IRCCS Ospedale San Raffaele/Università Vita-Salute San Raffaele , Milan, Italy . 2. 2 Metalloid Transport Group, Leibniz Institute of Plant Genetics and Crop Plant Research , Gatersleben, Germany . 3. 3 Department of Molecular Medicine, University of Pavia , Pavia, Italy . 4. 4 Cell Biology Unit, IRCCS AOU San Martino-IST , Genoa, Italy .
Abstract
UNLABELLED: 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. AIMS: In this study, we investigated whether and how the transport of H2O2 through plasma membrane AQP8 is regulated, particularly during cell stress. RESULTS: 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 Neither H2O2 nor water transport is impaired in stressed cells expressing a mutant AQP8, in which cysteine 53 had been replaced by serine.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. INNOVATION AND CONCLUSION: 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.
UNLABELLED: 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. AIMS: In this study, we investigated whether and how the transport of H2O2 through plasma membrane AQP8 is regulated, particularly during cell stress. RESULTS: 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. INNOVATION AND CONCLUSION: 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: Garrett J DeYulia; Juan M Cárcamo; Oriana Bórquez-Ojeda; Christopher C Shelton; David W Golde Journal: Proc Natl Acad Sci U S A Date: 2005-03-28 Impact factor: 11.205
Authors: Kimberly J Nelson; Chananat Klomsiri; Simona G Codreanu; Laura Soito; Daniel C Liebler; Leann C Rogers; Larry W Daniel; Leslie B Poole Journal: Methods Enzymol Date: 2010 Impact factor: 1.600
Authors: Markus Dagnell; Qing Cheng; Syed Husain Mustafa Rizvi; Paul E Pace; Benoit Boivin; Christine C Winterbourn; Elias S J Arnér Journal: J Biol Chem Date: 2019-06-13 Impact factor: 5.157
Authors: Carlos Henríquez-Olguín; Susanna Boronat; Claudio Cabello-Verrugio; Enrique Jaimovich; Elena Hidalgo; Thomas E Jensen Journal: Antioxid Redox Signal Date: 2019-11-01 Impact factor: 8.401