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Obacunone protects retinal pigment epithelium cells from ultra-violet radiation-induced oxidative injury

Ultra-violet (UV) radiation (UVR) causes significant oxidative injury to retinal pigment epithelium (RPE) cells. Obacunone is a highly oxygenated triterpenoid limonoid compound with various pharmacological properties. Its potential effect in RPE cells has not been studied thus far. Here in ARPE-19 c...

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Autores principales: Huang, Da-Rui, Dai, Chang-Ming, Li, Shu-Yan, Li, Xiao-Feng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8109142/
https://www.ncbi.nlm.nih.gov/pubmed/33535179
http://dx.doi.org/10.18632/aging.202437
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author Huang, Da-Rui
Dai, Chang-Ming
Li, Shu-Yan
Li, Xiao-Feng
author_facet Huang, Da-Rui
Dai, Chang-Ming
Li, Shu-Yan
Li, Xiao-Feng
author_sort Huang, Da-Rui
collection PubMed
description Ultra-violet (UV) radiation (UVR) causes significant oxidative injury to retinal pigment epithelium (RPE) cells. Obacunone is a highly oxygenated triterpenoid limonoid compound with various pharmacological properties. Its potential effect in RPE cells has not been studied thus far. Here in ARPE-19 cells and primary murine RPE cells, obacunone potently inhibited UVR-induced reactive oxygen species accumulation, mitochondrial depolarization, lipid peroxidation and single strand DNA accumulation. UVR-induced RPE cell death and apoptosis were largely alleviated by obacunone. Obacunone activated Nrf2 signaling cascade in RPE cells, causing Keap1-Nrf2 disassociation, Nrf2 protein stabilization and nuclear translocation. It promoted transcription and expression of antioxidant responsive element-dependent genes. Nrf2 silencing or CRISPR/Cas9-induced Nrf2 knockout almost reversed obacunone-induced RPE cytoprotection against UVR. Forced activation of Nrf2 cascade, by Keap1 knockout, similarly protected RPE cells from UVR. Importantly, obacunone failed to offer further RPE cytoprotection against UVR in Keap1-knockout cells. In vivo, intravitreal injection of obacunone largely inhibited light-induced retinal damage. Collectively, obacunone protects RPE cells from UVR-induced oxidative injury through activation of Nrf2 signaling cascade.
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spelling pubmed-81091422021-05-12 Obacunone protects retinal pigment epithelium cells from ultra-violet radiation-induced oxidative injury Huang, Da-Rui Dai, Chang-Ming Li, Shu-Yan Li, Xiao-Feng Aging (Albany NY) Research Paper Ultra-violet (UV) radiation (UVR) causes significant oxidative injury to retinal pigment epithelium (RPE) cells. Obacunone is a highly oxygenated triterpenoid limonoid compound with various pharmacological properties. Its potential effect in RPE cells has not been studied thus far. Here in ARPE-19 cells and primary murine RPE cells, obacunone potently inhibited UVR-induced reactive oxygen species accumulation, mitochondrial depolarization, lipid peroxidation and single strand DNA accumulation. UVR-induced RPE cell death and apoptosis were largely alleviated by obacunone. Obacunone activated Nrf2 signaling cascade in RPE cells, causing Keap1-Nrf2 disassociation, Nrf2 protein stabilization and nuclear translocation. It promoted transcription and expression of antioxidant responsive element-dependent genes. Nrf2 silencing or CRISPR/Cas9-induced Nrf2 knockout almost reversed obacunone-induced RPE cytoprotection against UVR. Forced activation of Nrf2 cascade, by Keap1 knockout, similarly protected RPE cells from UVR. Importantly, obacunone failed to offer further RPE cytoprotection against UVR in Keap1-knockout cells. In vivo, intravitreal injection of obacunone largely inhibited light-induced retinal damage. Collectively, obacunone protects RPE cells from UVR-induced oxidative injury through activation of Nrf2 signaling cascade. Impact Journals 2021-02-01 /pmc/articles/PMC8109142/ /pubmed/33535179 http://dx.doi.org/10.18632/aging.202437 Text en Copyright: © 2021 Huang et al. https://creativecommons.org/licenses/by/3.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Huang, Da-Rui
Dai, Chang-Ming
Li, Shu-Yan
Li, Xiao-Feng
Obacunone protects retinal pigment epithelium cells from ultra-violet radiation-induced oxidative injury
title Obacunone protects retinal pigment epithelium cells from ultra-violet radiation-induced oxidative injury
title_full Obacunone protects retinal pigment epithelium cells from ultra-violet radiation-induced oxidative injury
title_fullStr Obacunone protects retinal pigment epithelium cells from ultra-violet radiation-induced oxidative injury
title_full_unstemmed Obacunone protects retinal pigment epithelium cells from ultra-violet radiation-induced oxidative injury
title_short Obacunone protects retinal pigment epithelium cells from ultra-violet radiation-induced oxidative injury
title_sort obacunone protects retinal pigment epithelium cells from ultra-violet radiation-induced oxidative injury
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8109142/
https://www.ncbi.nlm.nih.gov/pubmed/33535179
http://dx.doi.org/10.18632/aging.202437
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