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


Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
24 06 2019
Historique:
received: 16 11 2018
accepted: 11 06 2019
entrez: 26 6 2019
pubmed: 27 6 2019
medline: 21 10 2020
Statut: epublish

Résumé

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.

Identifiants

pubmed: 31235776
doi: 10.1038/s41598-019-45669-z
pii: 10.1038/s41598-019-45669-z
pmc: PMC6591216
doi:

Substances chimiques

DNA, Mitochondrial 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

9103

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Auteurs

Kentaro Ariyoshi (K)

Department of Radiation Biology, Institute of Radiation Emergency Medicine, Hirosaki University, 66-1 Hon-cho, Hirosaki, 036-8564, Japan. ariyoshi@hirosaki-u.ac.jp.

Tomisato Miura (T)

Department of Biomedical Sciences, Hirosaki University Graduate School of Health Sciences, 66-1 Hon-cho, Hirosaki, 036-8564, Japan.

Kosuke Kasai (K)

Department of Biomedical Sciences, Hirosaki University Graduate School of Health Sciences, 66-1 Hon-cho, Hirosaki, 036-8564, Japan.

Yohei Fujishima (Y)

Department of Biomedical Sciences, Hirosaki University Graduate School of Health Sciences, 66-1 Hon-cho, Hirosaki, 036-8564, Japan.

Akifumi Nakata (A)

Department of Basic Pharmacy, Hokkaido Pharmaceutical University School of Pharmacy, Maeda 7-jo 15-4-1, Teine-ku, Otaru, Sapporo, 006-8590, Japan.

Mitsuaki Yoshida (M)

Department of Radiation Biology, Institute of Radiation Emergency Medicine, Hirosaki University, 66-1 Hon-cho, Hirosaki, 036-8564, Japan. myoshida@hirosaki-u.ac.jp.

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Classifications MeSH