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Neuroprotective role of retinal SIRT3 against acute photo-stress

SIRT3 is a key regulator of mitochondrial reactive oxygen species as well as mitochondrial function. The retina is one of the highest energy-demanding tissues, in which the regulation of reactive oxygen species is critical to prevent retinal neurodegeneration. Although previous reports have demonstr...

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Autores principales: Ban, Norimitsu, Ozawa, Yoko, Osada, Hideto, Lin, Jonathan B., Toda, Eriko, Watanabe, Mitsuhiro, Yuki, Kenya, Kubota, Shunsuke, Apte, Rajendra S., Tsubota, Kazuo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5712523/
https://www.ncbi.nlm.nih.gov/pubmed/29214052
http://dx.doi.org/10.1038/s41514-017-0017-8
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author Ban, Norimitsu
Ozawa, Yoko
Osada, Hideto
Lin, Jonathan B.
Toda, Eriko
Watanabe, Mitsuhiro
Yuki, Kenya
Kubota, Shunsuke
Apte, Rajendra S.
Tsubota, Kazuo
author_facet Ban, Norimitsu
Ozawa, Yoko
Osada, Hideto
Lin, Jonathan B.
Toda, Eriko
Watanabe, Mitsuhiro
Yuki, Kenya
Kubota, Shunsuke
Apte, Rajendra S.
Tsubota, Kazuo
author_sort Ban, Norimitsu
collection PubMed
description SIRT3 is a key regulator of mitochondrial reactive oxygen species as well as mitochondrial function. The retina is one of the highest energy-demanding tissues, in which the regulation of reactive oxygen species is critical to prevent retinal neurodegeneration. Although previous reports have demonstrated that SIRT3 is highly expressed in the retina and important in neuroprotection, function of SIRT3 in regulating reactive oxygen species in the retina is largely unknown. In this study, we investigated the role of retinal SIRT3 in a light-induced retinal degeneration model using SIRT3 knockout mice. We demonstrate that SIRT3 deficiency causes acute reactive oxygen species accumulation and endoplasmic reticulum stress in the retina after the light exposure, which leads to increased photoreceptor death, retinal thinning, and decreased retinal function. Using a photoreceptor-derived cell line, we revealed that reactive oxygen species were the upstream initiators of endoplasmic reticulum stress. Under SIRT3 knockdown condition, we demonstrated that decreased superoxide dismutase 2 activity led to elevated intracellular reactive oxygen species. These studies have helped to elucidate the critical role of SIRT3 in photoreceptor neuronal survival, and suggest that SIRT3 might be a therapeutic target for oxidative stress-induced retinal disorders.
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spelling pubmed-57125232017-12-06 Neuroprotective role of retinal SIRT3 against acute photo-stress Ban, Norimitsu Ozawa, Yoko Osada, Hideto Lin, Jonathan B. Toda, Eriko Watanabe, Mitsuhiro Yuki, Kenya Kubota, Shunsuke Apte, Rajendra S. Tsubota, Kazuo NPJ Aging Mech Dis Article SIRT3 is a key regulator of mitochondrial reactive oxygen species as well as mitochondrial function. The retina is one of the highest energy-demanding tissues, in which the regulation of reactive oxygen species is critical to prevent retinal neurodegeneration. Although previous reports have demonstrated that SIRT3 is highly expressed in the retina and important in neuroprotection, function of SIRT3 in regulating reactive oxygen species in the retina is largely unknown. In this study, we investigated the role of retinal SIRT3 in a light-induced retinal degeneration model using SIRT3 knockout mice. We demonstrate that SIRT3 deficiency causes acute reactive oxygen species accumulation and endoplasmic reticulum stress in the retina after the light exposure, which leads to increased photoreceptor death, retinal thinning, and decreased retinal function. Using a photoreceptor-derived cell line, we revealed that reactive oxygen species were the upstream initiators of endoplasmic reticulum stress. Under SIRT3 knockdown condition, we demonstrated that decreased superoxide dismutase 2 activity led to elevated intracellular reactive oxygen species. These studies have helped to elucidate the critical role of SIRT3 in photoreceptor neuronal survival, and suggest that SIRT3 might be a therapeutic target for oxidative stress-induced retinal disorders. Nature Publishing Group UK 2017-12-04 /pmc/articles/PMC5712523/ /pubmed/29214052 http://dx.doi.org/10.1038/s41514-017-0017-8 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Ban, Norimitsu
Ozawa, Yoko
Osada, Hideto
Lin, Jonathan B.
Toda, Eriko
Watanabe, Mitsuhiro
Yuki, Kenya
Kubota, Shunsuke
Apte, Rajendra S.
Tsubota, Kazuo
Neuroprotective role of retinal SIRT3 against acute photo-stress
title Neuroprotective role of retinal SIRT3 against acute photo-stress
title_full Neuroprotective role of retinal SIRT3 against acute photo-stress
title_fullStr Neuroprotective role of retinal SIRT3 against acute photo-stress
title_full_unstemmed Neuroprotective role of retinal SIRT3 against acute photo-stress
title_short Neuroprotective role of retinal SIRT3 against acute photo-stress
title_sort neuroprotective role of retinal sirt3 against acute photo-stress
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5712523/
https://www.ncbi.nlm.nih.gov/pubmed/29214052
http://dx.doi.org/10.1038/s41514-017-0017-8
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