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

被引：85

作者：

Ariyoshi, Kentaro ^{[1
]}

Miura, Tomisato ^{[2
]}

Kasai, Kosuke ^{[2
]}

Fujishima, Yohei ^{[2
]}

Nakata, Akifumi ^{[3
]}

Yoshida, Mitsuaki ^{[1
]}

机构：

[1] Hirosaki Univ, Inst Radiat Emergency Med, Dept Radiat Biol, 66-1 Hon Cho, Hirosaki, Aomori 0368564, Japan

[2] Hirosaki Univ, Grad Sch Hlth Sci, Dept Biomed Sci, 66-1 Hon Cho, Hirosaki, Aomori 0368564, Japan

[3] Hokkaido Pharmaceut Univ, Sch Pharm, Dept Basic Pharm, Teine Ku, Maeda 7 Jo 15-4-1, Sapporo, Hokkaido 0068590, Japan

来源：

SCIENTIFIC REPORTS | 2019年 / 9卷 / 1期

基金：

日本学术振兴会;

关键词：

IONIZING-RADIATION; IN-VIVO; EXTRACELLULAR VESICLES; INDUCTION; RESPONSES; DAMAGE; IRRADIATION; AUTOPHAGY; PLASMA; INFLAMMATION;

D O I：

10.1038/s41598-019-45669-z

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

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 (rho 0) 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.

引用

页数：14

共 73 条

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