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Repair kinetics of DNA double-strand breaks and incidence of apoptosis in mouse neural stem/progenitor cells and their differentiated neurons exposed to ionizing radiation

Neuronal loss leads to neurodegenerative disorders, including Alzheimer’s disease, Parkinson’s disease and Huntington’s disease. Because of their long lifespans, neurons are assumed to possess highly efficient DNA repair ability and to be able to protect themselves from deleterious DNA damage such a...

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Autores principales: Kashiwagi, Hiroki, Shiraishi, Kazunori, Sakaguchi, Kenta, Nakahama, Tomoya, Kodama, Seiji
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5967548/
https://www.ncbi.nlm.nih.gov/pubmed/29351627
http://dx.doi.org/10.1093/jrr/rrx089
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author Kashiwagi, Hiroki
Shiraishi, Kazunori
Sakaguchi, Kenta
Nakahama, Tomoya
Kodama, Seiji
author_facet Kashiwagi, Hiroki
Shiraishi, Kazunori
Sakaguchi, Kenta
Nakahama, Tomoya
Kodama, Seiji
author_sort Kashiwagi, Hiroki
collection PubMed
description Neuronal loss leads to neurodegenerative disorders, including Alzheimer’s disease, Parkinson’s disease and Huntington’s disease. Because of their long lifespans, neurons are assumed to possess highly efficient DNA repair ability and to be able to protect themselves from deleterious DNA damage such as DNA double-strand breaks (DSBs) produced by intrinsic and extrinsic sources. However, it remains largely unknown whether the DSB repair ability of neurons is more efficient compared with that of other cells. Here, we investigated the repair kinetics of X-ray–induced DSBs in mouse neural cells by scoring the number of phosphorylated 53BP1 foci post irradiation. We found that p53-independent apoptosis was induced time dependently during differentiation from neural stem/progenitor cells (NSPCs) into neurons in culture for 48 h. DSB repair in neurons differentiated from NSPCs in culture was faster than that in mouse embryonic fibroblasts (MEFs), possibly due to the higher DNA-dependent protein kinase activity, but it was similar to that in NSPCs. Further, the incidence of p53-dependent apoptosis induced by X-irradiation in neurons was significantly higher than that in NSPCs. This difference in response of X-ray–induced apoptosis between neurons and NSPCs may reflect a difference in the fidelity of non-homologous end joining or a differential sensitivity to DNA damage other than DSBs.
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spelling pubmed-59675482018-06-04 Repair kinetics of DNA double-strand breaks and incidence of apoptosis in mouse neural stem/progenitor cells and their differentiated neurons exposed to ionizing radiation Kashiwagi, Hiroki Shiraishi, Kazunori Sakaguchi, Kenta Nakahama, Tomoya Kodama, Seiji J Radiat Res Regular Paper Neuronal loss leads to neurodegenerative disorders, including Alzheimer’s disease, Parkinson’s disease and Huntington’s disease. Because of their long lifespans, neurons are assumed to possess highly efficient DNA repair ability and to be able to protect themselves from deleterious DNA damage such as DNA double-strand breaks (DSBs) produced by intrinsic and extrinsic sources. However, it remains largely unknown whether the DSB repair ability of neurons is more efficient compared with that of other cells. Here, we investigated the repair kinetics of X-ray–induced DSBs in mouse neural cells by scoring the number of phosphorylated 53BP1 foci post irradiation. We found that p53-independent apoptosis was induced time dependently during differentiation from neural stem/progenitor cells (NSPCs) into neurons in culture for 48 h. DSB repair in neurons differentiated from NSPCs in culture was faster than that in mouse embryonic fibroblasts (MEFs), possibly due to the higher DNA-dependent protein kinase activity, but it was similar to that in NSPCs. Further, the incidence of p53-dependent apoptosis induced by X-irradiation in neurons was significantly higher than that in NSPCs. This difference in response of X-ray–induced apoptosis between neurons and NSPCs may reflect a difference in the fidelity of non-homologous end joining or a differential sensitivity to DNA damage other than DSBs. Oxford University Press 2018-05 2018-01-17 /pmc/articles/PMC5967548/ /pubmed/29351627 http://dx.doi.org/10.1093/jrr/rrx089 Text en © The Author(s) 2018. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Regular Paper
Kashiwagi, Hiroki
Shiraishi, Kazunori
Sakaguchi, Kenta
Nakahama, Tomoya
Kodama, Seiji
Repair kinetics of DNA double-strand breaks and incidence of apoptosis in mouse neural stem/progenitor cells and their differentiated neurons exposed to ionizing radiation
title Repair kinetics of DNA double-strand breaks and incidence of apoptosis in mouse neural stem/progenitor cells and their differentiated neurons exposed to ionizing radiation
title_full Repair kinetics of DNA double-strand breaks and incidence of apoptosis in mouse neural stem/progenitor cells and their differentiated neurons exposed to ionizing radiation
title_fullStr Repair kinetics of DNA double-strand breaks and incidence of apoptosis in mouse neural stem/progenitor cells and their differentiated neurons exposed to ionizing radiation
title_full_unstemmed Repair kinetics of DNA double-strand breaks and incidence of apoptosis in mouse neural stem/progenitor cells and their differentiated neurons exposed to ionizing radiation
title_short Repair kinetics of DNA double-strand breaks and incidence of apoptosis in mouse neural stem/progenitor cells and their differentiated neurons exposed to ionizing radiation
title_sort repair kinetics of dna double-strand breaks and incidence of apoptosis in mouse neural stem/progenitor cells and their differentiated neurons exposed to ionizing radiation
topic Regular Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5967548/
https://www.ncbi.nlm.nih.gov/pubmed/29351627
http://dx.doi.org/10.1093/jrr/rrx089
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