Hydrogen Peroxide, Water Channels, and Tissue Injury

Abstract

Water channels, also known as aquaporins, were discovered by Peter C. Agre, the recipient of the 2003 Nobel Prize in Chemistry. In addition to facilitating transport of water, these channels have been shown to also mediate the diffusion of hydrogen peroxide across cell membranes and consequently control the biological functions of this important reactive oxygen species. Findings from multiple recent studies published in highly influential journals have further advanced our understanding on how to control the biological effects of hydrogen peroxide via targeting specific water channels. REFERENCES Hopkins RZ. Hydrogen Peroxide in biology and medicine: an overview. React Oxyg Species (Apex) 2017; 3(7):26–37. doi: https://dx.doi.org/10.20455/ros.2017.809. Bienert GP, Moller AL, Kristiansen KA, Schulz A, Moller IM, Schjoerring JK, et al. Specific aquaporins facilitate the diffusion of hydrogen peroxide across membranes. J Biol Chem 2007; 282(2):1183‒92. doi: https://dx.doi.org/10.1074/jbc.M603761200. Miller EW, Dickinson BC, Chang CJ. Aquaporin-3 mediates hydrogen peroxide uptake to regulate downstream intracellular signaling. Proc Natl Acad Sci USA 2010; 107(36):15681‒6. doi: https://dx.doi.org/10.1073/pnas.1005776107. Watanabe S, Moniaga CS, Nielsen S, Hara-Chikuma M. Aquaporin-9 facilitates membrane transport of hydrogen peroxide in mammalian cells. Biochem Biophys Res Commun 2016; 471(1):191‒7. doi: https://dx.doi.org/10.1016/j.bbrc.2016.01.153. Hara-Chikuma M, Chikuma S, Sugiyama Y, Kabashima K, Verkman AS, Inoue S, et al. Chemokine-dependent T cell migration requires aquaporin-3-mediated hydrogen peroxide uptake. J Exp Med 2012; 209(10):1743‒52. doi: https://dx.doi.org/10.1084/jem.20112398. Hara-Chikuma M, Satooka H, Watanabe S, Honda T, Miyachi Y, Watanabe T, et al. Aquaporin-3-mediated hydrogen peroxide transport is required for NF-kappaB signalling in keratinocytes and development of psoriasis. Nat Commun 2015; 6:7454. doi: https://dx.doi.org/10.1038/ncomms8454. Satooka H, Hara-Chikuma M. Aquaporin-3 controls breast cancer cell migration by regulating hydrogen peroxide transport and its downstream cell signaling. Mol Cell Biol 2016; 36(7):1206‒18. doi: https://dx.doi.org/10.1128/MCB.00971-15. Montiel V, Bella R, Michel LYM, Esfahani H, De Mulder D, Robinson EL, et al. Inhibition of aquaporin-1 prevents myocardial remodeling by blocking the transmembrane transport of hydrogen peroxide. Sci Transl Med 2020; 12(564). doi: https://dx.doi.org/10.1126/scitranslmed.aay2176. Steinhorn B, Sorrentino A, Badole S, Bogdanova Y, Belousov V, Michel T. Chemogenetic generation of hydrogen peroxide in the heart induces severe cardiac dysfunction. Nat Commun 2018; 9(1):4044. doi: https://dx.doi.org/10.1038/s41467-018-06533-2. Hara-Chikuma M, Tanaka M, Verkman AS, Yasui M. Inhibition of aquaporin-3 in macrophages by a monoclonal antibody as potential therapy for liver injury. Nat Commun 2020; 11(1):5666. doi: https://dx.doi.org/10.1038/s41467-020-19491-5. Hansson GK. Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med 2005; 352(16):1685‒95. doi: https://dx.doi.org/10.1056/NEJMra043430. Perry VH, Nicoll JA, Holmes C. Microglia in neurodegenerative disease. Nat Rev Neurol 2010; 6(4):193‒201. doi: https://dx.doi.org/10.1038/nrneurol.2010.17.