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

ABSTRACT: High levels of reactive oxygen species such as hydrogen peroxide (H₂O₂) 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 H₂O₂ 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 H₂O₂ transport and function as peroxiporins. Human lens epithelial cells expressing AQP1, AQP5 and AQP8, when treated with 50 μM HgCl₂ water channel inhibitor showed a significant reduction in H₂O₂ transport. Data obtained from the experiments involving H₂O₂-degrading enzyme glutathione peroxidase 1 (GPX1) knockout lenses showed H₂O₂ accumulation, suggesting H₂O₂ 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 H₂O₂ 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 H₂O₂ homeostasis to prevent oxidative stress, highlighting AQPs and GPX1 as promising therapeutic drug targets to delay/treat/prevent age-related lens cataracts.

SUBMITTER: Varadaraj K

PROVIDER: S-EPMC7085977 | biostudies-literature |

REPOSITORIES: biostudies-literature

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