Oxidative Stress and Gene Expression Modifications Mediated by Extracellular Vesicles: An In Vivo Study of the Radiation-Induced Bystander Effect

Radiation-induced bystander effect is a biological response in nonirradiated cells receiving signals from cells exposed to ionising radiation. The aim of this in vivo study was to analyse whether extracellular vesicles (EVs) originating from irradiated mice could induce modifications in the redox st...

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Main Authors: Rita Hargitai, Dávid Kis, Eszter Persa, Tünde Szatmári, Géza Sáfrány, Katalin Lumniczky
Format: Article
Language:English
Published: MDPI AG 2021-01-01
Series:Antioxidants
Subjects:
Online Access:https://www.mdpi.com/2076-3921/10/2/156
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spelling doaj-50e30c98dcf54d4faf0bfb1ddd67c1742021-01-22T00:06:58ZengMDPI AGAntioxidants2076-39212021-01-011015615610.3390/antiox10020156Oxidative Stress and Gene Expression Modifications Mediated by Extracellular Vesicles: An In Vivo Study of the Radiation-Induced Bystander EffectRita Hargitai0Dávid Kis1Eszter Persa2Tünde Szatmári3Géza Sáfrány4Katalin Lumniczky5Radiation Medicine Unit, Department of Radiobiology and Radiohygiene, National Public Health Centre, 1221 Budapest, HungaryRadiation Medicine Unit, Department of Radiobiology and Radiohygiene, National Public Health Centre, 1221 Budapest, HungaryRadiation Medicine Unit, Department of Radiobiology and Radiohygiene, National Public Health Centre, 1221 Budapest, HungaryRadiation Medicine Unit, Department of Radiobiology and Radiohygiene, National Public Health Centre, 1221 Budapest, HungaryRadiation Medicine Unit, Department of Radiobiology and Radiohygiene, National Public Health Centre, 1221 Budapest, HungaryRadiation Medicine Unit, Department of Radiobiology and Radiohygiene, National Public Health Centre, 1221 Budapest, HungaryRadiation-induced bystander effect is a biological response in nonirradiated cells receiving signals from cells exposed to ionising radiation. The aim of this in vivo study was to analyse whether extracellular vesicles (EVs) originating from irradiated mice could induce modifications in the redox status and expression of radiation-response genes in bystander mice. C57BL/6 mice were whole-body irradiated with 0.1-Gy and 2-Gy X-rays, and EVs originating from mice irradiated with the same doses were injected into naïve, bystander mice. Lipid peroxidation in the spleen and plasma reactive oxygen metabolite (ROM) levels increased 24 h after irradiation with 2 Gy. The expression of antioxidant enzyme genes and inducible nitric oxide synthase 2 (iNOS2) decreased, while cell cycle arrest-, senescence- and apoptosis-related genes were upregulated after irradiation with 2 Gy. In bystander mice, no significant alterations were observed in lipid peroxidation or in the expression of genes connected to cell cycle arrest, senescence and apoptosis. However, there was a systemic increase in the circulating ROM level after an intravenous EV injection, and EVs originating from 2-Gy-irradiated mice caused a reduced expression of antioxidant enzyme genes and iNOS2 in bystander mice. In conclusion, we showed that ionising radiation-induced alterations in the cellular antioxidant system can be transmitted in vivo in a bystander manner through EVs originating from directly irradiated animals.https://www.mdpi.com/2076-3921/10/2/156antioxidant enzymesapoptosisDNA damage repairextracellular vesiclesgene expressionionising radiation
collection DOAJ
language English
format Article
sources DOAJ
author Rita Hargitai
Dávid Kis
Eszter Persa
Tünde Szatmári
Géza Sáfrány
Katalin Lumniczky
spellingShingle Rita Hargitai
Dávid Kis
Eszter Persa
Tünde Szatmári
Géza Sáfrány
Katalin Lumniczky
Oxidative Stress and Gene Expression Modifications Mediated by Extracellular Vesicles: An In Vivo Study of the Radiation-Induced Bystander Effect
Antioxidants
antioxidant enzymes
apoptosis
DNA damage repair
extracellular vesicles
gene expression
ionising radiation
author_facet Rita Hargitai
Dávid Kis
Eszter Persa
Tünde Szatmári
Géza Sáfrány
Katalin Lumniczky
author_sort Rita Hargitai
title Oxidative Stress and Gene Expression Modifications Mediated by Extracellular Vesicles: An In Vivo Study of the Radiation-Induced Bystander Effect
title_short Oxidative Stress and Gene Expression Modifications Mediated by Extracellular Vesicles: An In Vivo Study of the Radiation-Induced Bystander Effect
title_full Oxidative Stress and Gene Expression Modifications Mediated by Extracellular Vesicles: An In Vivo Study of the Radiation-Induced Bystander Effect
title_fullStr Oxidative Stress and Gene Expression Modifications Mediated by Extracellular Vesicles: An In Vivo Study of the Radiation-Induced Bystander Effect
title_full_unstemmed Oxidative Stress and Gene Expression Modifications Mediated by Extracellular Vesicles: An In Vivo Study of the Radiation-Induced Bystander Effect
title_sort oxidative stress and gene expression modifications mediated by extracellular vesicles: an in vivo study of the radiation-induced bystander effect
publisher MDPI AG
series Antioxidants
issn 2076-3921
publishDate 2021-01-01
description Radiation-induced bystander effect is a biological response in nonirradiated cells receiving signals from cells exposed to ionising radiation. The aim of this in vivo study was to analyse whether extracellular vesicles (EVs) originating from irradiated mice could induce modifications in the redox status and expression of radiation-response genes in bystander mice. C57BL/6 mice were whole-body irradiated with 0.1-Gy and 2-Gy X-rays, and EVs originating from mice irradiated with the same doses were injected into naïve, bystander mice. Lipid peroxidation in the spleen and plasma reactive oxygen metabolite (ROM) levels increased 24 h after irradiation with 2 Gy. The expression of antioxidant enzyme genes and inducible nitric oxide synthase 2 (iNOS2) decreased, while cell cycle arrest-, senescence- and apoptosis-related genes were upregulated after irradiation with 2 Gy. In bystander mice, no significant alterations were observed in lipid peroxidation or in the expression of genes connected to cell cycle arrest, senescence and apoptosis. However, there was a systemic increase in the circulating ROM level after an intravenous EV injection, and EVs originating from 2-Gy-irradiated mice caused a reduced expression of antioxidant enzyme genes and iNOS2 in bystander mice. In conclusion, we showed that ionising radiation-induced alterations in the cellular antioxidant system can be transmitted in vivo in a bystander manner through EVs originating from directly irradiated animals.
topic antioxidant enzymes
apoptosis
DNA damage repair
extracellular vesicles
gene expression
ionising radiation
url https://www.mdpi.com/2076-3921/10/2/156
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