Lens aquaporins function as peroxiporins to facilitate membrane transport of hydrogen peroxide.

Publisher: Elsevier Country of Publication: United States NLM ID: 0372516 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1090-2104 (Electronic) Linking ISSN: 0006291X NLM ISO Abbreviation: Biochem Biophys Res Commun Subsets: MEDLINE

Publication: <2002- >: San Diego, CA : Elsevier
Original Publication: New York, Academic Press.

Aquaporins/*metabolism ; Hydrogen Peroxide/*metabolism ; Lens, Crystalline/*metabolism; Animals ; Aquaporin 1/metabolism ; Aquaporin 5/metabolism ; Biological Transport ; Cell Line ; Cell Membrane/metabolism ; Dogs ; Eye Proteins/metabolism ; Humans ; Madin Darby Canine Kidney Cells ; Mice, Inbred C57BL

High levels of reactive oxygen species such as hydrogen peroxide (H 2 O 2 ) cause oxidative stress in the lens and lead to cataractogenesis. The present investigation was undertaken to find out whether the mammalian lens aquaporins (AQPs) 0, 1, and 5 perform H 2 O 2 transport across the plasma membrane to reduce oxidative stress. Our in vitro cell culture and ex vivo lens experiments demonstrated that in addition to the established water transport role, mouse AQP0, AQP1 and AQP5 facilitate transmembrane H 2 O 2 transport and function as peroxiporins. Human lens epithelial cells expressing AQP1, AQP5 and AQP8, when treated with 50 μM HgCl 2 water channel inhibitor showed a significant reduction in H 2 O 2 transport. Data obtained from the experiments involving H 2 O 2 -degrading enzyme glutathione peroxidase 1 (GPX1) knockout lenses showed H 2 O 2 accumulation, suggesting H 2 O 2 transport level by AQPs in the lens is regulated by GPX1. Under hyperglycemic conditions, there was an increased loss of transparency, and enhanced production and retention of H 2 O 2 in AQP5 ^-/- lenses compared to similarly-treated WT lenses. Overall, the results show that lens AQPs function as peroxiporins and cooperate with GPX1 to maintain lens H 2 O 2 homeostasis to prevent oxidative stress, highlighting AQPs and GPX1 as promising therapeutic drug targets to delay/treat/prevent age-related lens cataracts.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2020 Elsevier Inc. All rights reserved.)

Exp Eye Res. 1991 Oct;53(4):503-6. (PMID: 1936185)
Invest Ophthalmol Vis Sci. 2019 Mar 1;60(4):858-867. (PMID: 30821811)
J Membr Biol. 2007 Mar;216(1):1-16. (PMID: 17568975)
Biochim Biophys Acta. 2015 Sep;1850(9):1786-94. (PMID: 25982446)
Invest Ophthalmol Vis Sci. 2005 Apr;46(4):1393-402. (PMID: 15790907)
Biochem Biophys Res Commun. 2013 Nov 15;441(2):333-8. (PMID: 24148248)
Biochem Biophys Res Commun. 2014 Oct 3;452(4):986-91. (PMID: 25229686)
Mutat Res. 2019 Jan - Mar;779:68-81. (PMID: 31097153)
Am J Physiol Cell Physiol. 2018 Feb 1;314(2):C191-C201. (PMID: 29118028)
Exp Eye Res. 2001 May;72(5):533-45. (PMID: 11311045)
Biochem Biophys Res Commun. 2019 Apr 9;511(3):626-630. (PMID: 30826060)
Free Radic Biol Med. 1987;3(6):371-7. (PMID: 3322949)
Proc Natl Acad Sci U S A. 2010 Sep 7;107(36):15681-6. (PMID: 20724658)
Exp Eye Res. 2017 Mar;156:112-116. (PMID: 27260484)
Physiol Genomics. 2001 Dec 21;7(2):179-86. (PMID: 11773604)
Invest Ophthalmol Vis Sci. 2019 Jun 3;60(7):2525-2531. (PMID: 31195409)
Biochem Biophys Res Commun. 2018 Nov 17;506(1):284-289. (PMID: 30348525)
Antioxid Redox Signal. 2009 Feb;11(2):339-53. (PMID: 18831679)
Exp Eye Res. 2005 May;80(5):709-25. (PMID: 15862178)
FEBS Lett. 1997 Sep 15;414(3):552-6. (PMID: 9323034)
Nat Chem Biol. 2011 Jul 18;7(8):504-11. (PMID: 21769097)
Invest Ophthalmol Vis Sci. 2017 Dec 1;58(14):6006-6019. (PMID: 29196765)
Biochem Biophys Res Commun. 2009 Dec 18;390(3):1034-9. (PMID: 19857466)
J Biol Chem. 2007 Jan 12;282(2):1183-92. (PMID: 17105724)
FEBS J. 2014 Feb;281(3):647-56. (PMID: 24286224)
Physiol Rev. 1997 Jan;77(1):21-50. (PMID: 9016299)
FASEB J. 1995 Sep;9(12):1173-82. (PMID: 7672510)
J Biol Chem. 2001 Jun 29;276(26):23413-20. (PMID: 11290736)
Exp Eye Res. 2019 Aug;185:107585. (PMID: 30790544)
Ophthalmologica. 1997;211(3):192-200. (PMID: 9176901)
Int J Mol Sci. 2017 Dec 12;18(12):. (PMID: 29231874)
Biochem Biophys Res Commun. 2016 Feb 26;471(1):191-7. (PMID: 26837049)
Exp Eye Res. 1981 Dec;33(6):673-81. (PMID: 7318962)
Oxid Med Cell Longev. 2017;2017:8416763. (PMID: 28819546)
J Membr Biol. 2009 Jan;227(1):25-37. (PMID: 19067024)
J Biol Chem. 1998 Feb 20;273(8):4296-9. (PMID: 9468475)
Invest Ophthalmol Vis Sci. 2003 May;44(5):2084-93. (PMID: 12714647)
Biochem Biophys Res Commun. 2015 Jul 10;462(4):339-45. (PMID: 25960294)
J Biol Chem. 1997 Jun 27;272(26):16644-51. (PMID: 9195979)
Biochim Biophys Acta. 2014 May;1840(5):1513-23. (PMID: 24184915)
Mol Vis. 2012;18:957-67. (PMID: 22550388)
Int J Mol Sci. 2019 Jul 26;20(15):. (PMID: 31357514)
Invest Ophthalmol Vis Sci. 2015 Dec;56(13):7868-74. (PMID: 26658510)
Antioxid Redox Signal. 2005 May-Jun;7(5-6):526-37. (PMID: 15889998)
Mol Cell Biochem. 2015 Mar;401(1-2):87-95. (PMID: 25445170)
Invest Ophthalmol Vis Sci. 2019 Sep 3;60(12):4021-4032. (PMID: 31560767)
Biochim Biophys Acta. 2014 May;1840(5):1596-604. (PMID: 24060746)
Biochim Biophys Acta. 2014 Sep;1840(9):2862-77. (PMID: 24821012)

R01 EY026155 United States EY NEI NIH HHS; R01 EY033346 United States EY NEI NIH HHS

Keywords: AQP1; AQP5; AQP8; H(2)O(2); Lens AQP0; Peroxiporin

0 (Aquaporin 5)
0 (Aquaporins)
0 (Eye Proteins)
0 (aquaporin 0)
0 (aquaporin 8)
146410-94-8 (Aquaporin 1)
BBX060AN9V (Hydrogen Peroxide)

Date Created: 20200218 Date Completed: 20201026 Latest Revision: 20220826

20240829

PMC7085977

10.1016/j.bbrc.2020.02.031

32063362