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LncRNA NORAD defects deteriorate the formation of age-related macular degeneration

Long noncoding RNAs (lncRNAs) play important roles in the development of age-related macular degeneration (AMD). However, the effect of long non-coding RNA activated by DNA damage (NORAD) on AMD remains unknown. This study aimed to investigate the effect of NORAD on RPE cell senescence and degenerat...

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Autores principales: Zhang, Jinfeng, Jiang, Jing, Zhou, Hongyu, Li, Shenjun, Bian, Weihua, Hu, Lifu, Zhang, Daolai, Xu, Cong, Sun, Yeying
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10457045/
https://www.ncbi.nlm.nih.gov/pubmed/37517088
http://dx.doi.org/10.18632/aging.204917
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author Zhang, Jinfeng
Jiang, Jing
Zhou, Hongyu
Li, Shenjun
Bian, Weihua
Hu, Lifu
Zhang, Daolai
Xu, Cong
Sun, Yeying
author_facet Zhang, Jinfeng
Jiang, Jing
Zhou, Hongyu
Li, Shenjun
Bian, Weihua
Hu, Lifu
Zhang, Daolai
Xu, Cong
Sun, Yeying
author_sort Zhang, Jinfeng
collection PubMed
description Long noncoding RNAs (lncRNAs) play important roles in the development of age-related macular degeneration (AMD). However, the effect of long non-coding RNA activated by DNA damage (NORAD) on AMD remains unknown. This study aimed to investigate the effect of NORAD on RPE cell senescence and degeneration. Irradiated adult retinal pigment epithelial cell line-19 (ARPE-19) and sodium iodate-treated mice were used as in vitro and in vivo AMD models. Results showed that irradiation-induced AMD characteristics of ARPE-19 and NORAD-knockdown aggravated cell cycle arrest in the G2/M phase, cell apoptosis and cell senescence along with the increased expression of phosphorylated P53 (p-P53) and P21. AMD factors C3, ICAM-1, APP, APOE, and VEGF-A were also increased by NORAD-knockdown. Moreover, NORAD-knockdown increased irradiation-induced reduction of mitochondrial homeostasis factors, (i.e., TFAM and POLG) and mitochondrial respiratory chain complex genes (i.e., ND1 and ND5) along with mitochondrial reactive oxygen species (ROS). We also identified a strong interaction of NORAD and PGC-1α and sirtuin 1 (SIRT1) in ARPE-19; that is, NORAD knockdown increases the acetylation of PGC-1α. In NORAD knockout mice, NORAD-knockout accelerated the sodium iodate-reduced retinal thickness reduction, function impairment and loss of retinal pigment in the fundus. Therefore, NORAD-knockdown accelerates retinal cell senescence, apoptosis, and AMD markers via PGC-1α acetylation, mitochondrial ROS, and the p-P53–P21signaling pathway, in which NORAD-mediated effect on PGC-1α acetylation might occur through the direct interaction with PGC-1α and SIRT1.
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spelling pubmed-104570452023-08-26 LncRNA NORAD defects deteriorate the formation of age-related macular degeneration Zhang, Jinfeng Jiang, Jing Zhou, Hongyu Li, Shenjun Bian, Weihua Hu, Lifu Zhang, Daolai Xu, Cong Sun, Yeying Aging (Albany NY) Research Paper Long noncoding RNAs (lncRNAs) play important roles in the development of age-related macular degeneration (AMD). However, the effect of long non-coding RNA activated by DNA damage (NORAD) on AMD remains unknown. This study aimed to investigate the effect of NORAD on RPE cell senescence and degeneration. Irradiated adult retinal pigment epithelial cell line-19 (ARPE-19) and sodium iodate-treated mice were used as in vitro and in vivo AMD models. Results showed that irradiation-induced AMD characteristics of ARPE-19 and NORAD-knockdown aggravated cell cycle arrest in the G2/M phase, cell apoptosis and cell senescence along with the increased expression of phosphorylated P53 (p-P53) and P21. AMD factors C3, ICAM-1, APP, APOE, and VEGF-A were also increased by NORAD-knockdown. Moreover, NORAD-knockdown increased irradiation-induced reduction of mitochondrial homeostasis factors, (i.e., TFAM and POLG) and mitochondrial respiratory chain complex genes (i.e., ND1 and ND5) along with mitochondrial reactive oxygen species (ROS). We also identified a strong interaction of NORAD and PGC-1α and sirtuin 1 (SIRT1) in ARPE-19; that is, NORAD knockdown increases the acetylation of PGC-1α. In NORAD knockout mice, NORAD-knockout accelerated the sodium iodate-reduced retinal thickness reduction, function impairment and loss of retinal pigment in the fundus. Therefore, NORAD-knockdown accelerates retinal cell senescence, apoptosis, and AMD markers via PGC-1α acetylation, mitochondrial ROS, and the p-P53–P21signaling pathway, in which NORAD-mediated effect on PGC-1α acetylation might occur through the direct interaction with PGC-1α and SIRT1. Impact Journals 2023-07-29 /pmc/articles/PMC10457045/ /pubmed/37517088 http://dx.doi.org/10.18632/aging.204917 Text en Copyright: © 2023 Zhang 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
Zhang, Jinfeng
Jiang, Jing
Zhou, Hongyu
Li, Shenjun
Bian, Weihua
Hu, Lifu
Zhang, Daolai
Xu, Cong
Sun, Yeying
LncRNA NORAD defects deteriorate the formation of age-related macular degeneration
title LncRNA NORAD defects deteriorate the formation of age-related macular degeneration
title_full LncRNA NORAD defects deteriorate the formation of age-related macular degeneration
title_fullStr LncRNA NORAD defects deteriorate the formation of age-related macular degeneration
title_full_unstemmed LncRNA NORAD defects deteriorate the formation of age-related macular degeneration
title_short LncRNA NORAD defects deteriorate the formation of age-related macular degeneration
title_sort lncrna norad defects deteriorate the formation of age-related macular degeneration
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10457045/
https://www.ncbi.nlm.nih.gov/pubmed/37517088
http://dx.doi.org/10.18632/aging.204917
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