US EPA

6574995 

Journal Article 

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

Varadaraj, K; Kumari, SS; , 

2020 

Yes 

Biochemical and Biophysical Research Communications
ISSN: 0006-291X
EISSN: 1090-2104 

ACADEMIC PRESS INC ELSEVIER SCIENCE 

SAN DIEGO 

524 

4 

1025-1029 

English 

32063362 

10.1016/j.bbrc.2020.02.031 

WOS:000526795700035 

http://://WOS:000526795700035
Exit
 

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. 

Lens AQP0; Peroxiporin; c-terminal end; oxidative stress; water permeability; cataract; formation; refractive-index; transgenic mice; gap-junctions; expression; deficient; mechanism; Biochemistry & Molecular Biology; Biophysics