SLC4A11 depletion impairs NRF2 mediated antioxidant signaling and increases reactive oxygen species in human corneal endothelial cells during oxidative stress

Abstract Corneal endothelial dystrophy is a progressive disease with gradual loss of vision and characterized by degeneration and dysfunction of corneal endothelial cells. Mutations in SLC4A11, a Na+ dependent OH− transporter, cause congenital hereditary endothelial dystrophy (CHED) and Fuchs’ endot...

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Autores principales: Sanjukta Guha, Sunita Chaurasia, Charanya Ramachandran, Sanhita Roy
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Lenguaje:EN
Publicado: Nature Portfolio 2017
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Acceso en línea:https://doaj.org/article/76dab40d3a67497fab38540c11365b16
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spelling oai:doaj.org-article:76dab40d3a67497fab38540c11365b162021-12-02T12:31:59ZSLC4A11 depletion impairs NRF2 mediated antioxidant signaling and increases reactive oxygen species in human corneal endothelial cells during oxidative stress10.1038/s41598-017-03654-42045-2322https://doaj.org/article/76dab40d3a67497fab38540c11365b162017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03654-4https://doaj.org/toc/2045-2322Abstract Corneal endothelial dystrophy is a progressive disease with gradual loss of vision and characterized by degeneration and dysfunction of corneal endothelial cells. Mutations in SLC4A11, a Na+ dependent OH− transporter, cause congenital hereditary endothelial dystrophy (CHED) and Fuchs’ endothelial corneal dystrophy (FECD), the two most common forms of endothelial degeneration. Along with genetic factors, oxidative stress plays a role in pathogenesis of several corneal diseases. In this study we looked into the role of SLC4A11 in antioxidant stress response in human corneal endothelial cells (HCEnC). We found increased expression of SLC4A11 in presence of oxidative stress. Depletion of SLC4A11 using targeted siRNA, caused an increase in reactive oxygen species, cytochrome c, lowered mitochondrial membrane potential, and reduced cell viability during oxidative stress. Moreover, SLC4A11 was found to be necessary for NRF2 mediated antioxidant gene expression in HCEnC. On the other hand, over expression of SLC4A11 reduces reactive oxygen species levels and increases cell viability. Lastly, CHED tissue specimens show evidence of oxidative stress and reduced expression of NRF2. In conclusion, our data suggests a possible role of SLC4A11 in regulating oxidative stress, and might be responsible for both the etiology and treatment of corneal endothelial dystrophy.Sanjukta GuhaSunita ChaurasiaCharanya RamachandranSanhita RoyNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Sanjukta Guha
Sunita Chaurasia
Charanya Ramachandran
Sanhita Roy
SLC4A11 depletion impairs NRF2 mediated antioxidant signaling and increases reactive oxygen species in human corneal endothelial cells during oxidative stress
description Abstract Corneal endothelial dystrophy is a progressive disease with gradual loss of vision and characterized by degeneration and dysfunction of corneal endothelial cells. Mutations in SLC4A11, a Na+ dependent OH− transporter, cause congenital hereditary endothelial dystrophy (CHED) and Fuchs’ endothelial corneal dystrophy (FECD), the two most common forms of endothelial degeneration. Along with genetic factors, oxidative stress plays a role in pathogenesis of several corneal diseases. In this study we looked into the role of SLC4A11 in antioxidant stress response in human corneal endothelial cells (HCEnC). We found increased expression of SLC4A11 in presence of oxidative stress. Depletion of SLC4A11 using targeted siRNA, caused an increase in reactive oxygen species, cytochrome c, lowered mitochondrial membrane potential, and reduced cell viability during oxidative stress. Moreover, SLC4A11 was found to be necessary for NRF2 mediated antioxidant gene expression in HCEnC. On the other hand, over expression of SLC4A11 reduces reactive oxygen species levels and increases cell viability. Lastly, CHED tissue specimens show evidence of oxidative stress and reduced expression of NRF2. In conclusion, our data suggests a possible role of SLC4A11 in regulating oxidative stress, and might be responsible for both the etiology and treatment of corneal endothelial dystrophy.
format article
author Sanjukta Guha
Sunita Chaurasia
Charanya Ramachandran
Sanhita Roy
author_facet Sanjukta Guha
Sunita Chaurasia
Charanya Ramachandran
Sanhita Roy
author_sort Sanjukta Guha
title SLC4A11 depletion impairs NRF2 mediated antioxidant signaling and increases reactive oxygen species in human corneal endothelial cells during oxidative stress
title_short SLC4A11 depletion impairs NRF2 mediated antioxidant signaling and increases reactive oxygen species in human corneal endothelial cells during oxidative stress
title_full SLC4A11 depletion impairs NRF2 mediated antioxidant signaling and increases reactive oxygen species in human corneal endothelial cells during oxidative stress
title_fullStr SLC4A11 depletion impairs NRF2 mediated antioxidant signaling and increases reactive oxygen species in human corneal endothelial cells during oxidative stress
title_full_unstemmed SLC4A11 depletion impairs NRF2 mediated antioxidant signaling and increases reactive oxygen species in human corneal endothelial cells during oxidative stress
title_sort slc4a11 depletion impairs nrf2 mediated antioxidant signaling and increases reactive oxygen species in human corneal endothelial cells during oxidative stress
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/76dab40d3a67497fab38540c11365b16
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AT sunitachaurasia slc4a11depletionimpairsnrf2mediatedantioxidantsignalingandincreasesreactiveoxygenspeciesinhumancornealendothelialcellsduringoxidativestress
AT charanyaramachandran slc4a11depletionimpairsnrf2mediatedantioxidantsignalingandincreasesreactiveoxygenspeciesinhumancornealendothelialcellsduringoxidativestress
AT sanhitaroy slc4a11depletionimpairsnrf2mediatedantioxidantsignalingandincreasesreactiveoxygenspeciesinhumancornealendothelialcellsduringoxidativestress
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