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Radiation-Induced Bystander Effect is Mediated by Mitochondrial DNA in Exosome-Like Vesicles

Exosome-like vesicles (ELV) are involved in mediating radiation-induced bystander effect (RIBE). Here, we used ELV from control cell conditioned medium (CCCM) and from 4 Gy of X-ray irradiated cell conditioned medium (ICCM), which has been used to culture normal human fibroblast cells to examine the...

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Autores principales: Ariyoshi, Kentaro, Miura, Tomisato, Kasai, Kosuke, Fujishima, Yohei, Nakata, Akifumi, Yoshida, Mitsuaki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6591216/
https://www.ncbi.nlm.nih.gov/pubmed/31235776
http://dx.doi.org/10.1038/s41598-019-45669-z
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author Ariyoshi, Kentaro
Miura, Tomisato
Kasai, Kosuke
Fujishima, Yohei
Nakata, Akifumi
Yoshida, Mitsuaki
author_facet Ariyoshi, Kentaro
Miura, Tomisato
Kasai, Kosuke
Fujishima, Yohei
Nakata, Akifumi
Yoshida, Mitsuaki
author_sort Ariyoshi, Kentaro
collection PubMed
description Exosome-like vesicles (ELV) are involved in mediating radiation-induced bystander effect (RIBE). Here, we used ELV from control cell conditioned medium (CCCM) and from 4 Gy of X-ray irradiated cell conditioned medium (ICCM), which has been used to culture normal human fibroblast cells to examine the possibility of ELV mediating RIBE signals. We investigated whether ELV from 4 Gy irradiated mouse serum mediate RIBE signals. Induction of DNA damage was observed in cells that were treated with ICCM ELV and ELV from 4 Gy irradiated mouse serum. In addition, we treated CCCM ELV and ICCM ELV with RNases, DNases, and proteinases to determine which component of ELV is responsible for RIBE. Induction of DNA damage by ICCM ELV was not observed after treatment with DNases. After treatment, DNA damages were not induced in CCCM ELV or ICCM ELV from mitochondria depleted (ρ0) normal human fibroblast cells. Further, we found significant increase in mitochondrial DNA (mtDNA) in ICCM ELV and ELV from 4 Gy irradiated mouse serum. ELV carrying amplified mtDNA (ND1, ND5) induced DNA damage in treated cells. These data suggest that the secretion of mtDNA through exosomes is involved in mediating RIBE signals.
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spelling pubmed-65912162019-07-02 Radiation-Induced Bystander Effect is Mediated by Mitochondrial DNA in Exosome-Like Vesicles Ariyoshi, Kentaro Miura, Tomisato Kasai, Kosuke Fujishima, Yohei Nakata, Akifumi Yoshida, Mitsuaki Sci Rep Article Exosome-like vesicles (ELV) are involved in mediating radiation-induced bystander effect (RIBE). Here, we used ELV from control cell conditioned medium (CCCM) and from 4 Gy of X-ray irradiated cell conditioned medium (ICCM), which has been used to culture normal human fibroblast cells to examine the possibility of ELV mediating RIBE signals. We investigated whether ELV from 4 Gy irradiated mouse serum mediate RIBE signals. Induction of DNA damage was observed in cells that were treated with ICCM ELV and ELV from 4 Gy irradiated mouse serum. In addition, we treated CCCM ELV and ICCM ELV with RNases, DNases, and proteinases to determine which component of ELV is responsible for RIBE. Induction of DNA damage by ICCM ELV was not observed after treatment with DNases. After treatment, DNA damages were not induced in CCCM ELV or ICCM ELV from mitochondria depleted (ρ0) normal human fibroblast cells. Further, we found significant increase in mitochondrial DNA (mtDNA) in ICCM ELV and ELV from 4 Gy irradiated mouse serum. ELV carrying amplified mtDNA (ND1, ND5) induced DNA damage in treated cells. These data suggest that the secretion of mtDNA through exosomes is involved in mediating RIBE signals. Nature Publishing Group UK 2019-06-24 /pmc/articles/PMC6591216/ /pubmed/31235776 http://dx.doi.org/10.1038/s41598-019-45669-z Text en © The Author(s) 2019 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
Ariyoshi, Kentaro
Miura, Tomisato
Kasai, Kosuke
Fujishima, Yohei
Nakata, Akifumi
Yoshida, Mitsuaki
Radiation-Induced Bystander Effect is Mediated by Mitochondrial DNA in Exosome-Like Vesicles
title Radiation-Induced Bystander Effect is Mediated by Mitochondrial DNA in Exosome-Like Vesicles
title_full Radiation-Induced Bystander Effect is Mediated by Mitochondrial DNA in Exosome-Like Vesicles
title_fullStr Radiation-Induced Bystander Effect is Mediated by Mitochondrial DNA in Exosome-Like Vesicles
title_full_unstemmed Radiation-Induced Bystander Effect is Mediated by Mitochondrial DNA in Exosome-Like Vesicles
title_short Radiation-Induced Bystander Effect is Mediated by Mitochondrial DNA in Exosome-Like Vesicles
title_sort radiation-induced bystander effect is mediated by mitochondrial dna in exosome-like vesicles
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6591216/
https://www.ncbi.nlm.nih.gov/pubmed/31235776
http://dx.doi.org/10.1038/s41598-019-45669-z
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