A Proteomic Study Suggests Stress Granules as New Potential Actors in Radiation-Induced Bystander Effects
Besides the direct effects of radiations, indirect effects are observed within the surrounding non-irradiated area; irradiated cells relay stress signals in this close proximity, inducing the so-called radiation-induced bystander effect. These signals received by neighboring unirradiated cells induc...
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doaj-66cd70e1b71c4c33995a4b05dcf631c42021-08-06T15:24:52ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-07-01227957795710.3390/ijms22157957A Proteomic Study Suggests Stress Granules as New Potential Actors in Radiation-Induced Bystander EffectsMihaela Tudor0Antoine Gilbert1Charlotte Lepleux2Mihaela Temelie3Sonia Hem4Jean Armengaud5Emilie Brotin6Siamak Haghdoost7Diana Savu8François Chevalier9Department of Life and Environmental Physics, HoriaHulubei National Institute of Physics and Nuclear Engineering, 077125 Magurele, RomaniaUMR6252 CIMAP, Team Applications in Radiobiology with Accelerated Ions, CEA-CNRS-ENSICAEN-Université de Caen Normandie, 14000 Caen, FranceUMR6252 CIMAP, Team Applications in Radiobiology with Accelerated Ions, CEA-CNRS-ENSICAEN-Université de Caen Normandie, 14000 Caen, FranceDepartment of Life and Environmental Physics, HoriaHulubei National Institute of Physics and Nuclear Engineering, 077125 Magurele, RomaniaBPMP, Montpellier University, CNRS, INRAE, Institut Agro, 34000 Montpellier, FranceUniversité Paris-Saclay, CEA, INRAE, Département Médicaments et Technologies pour la Santé (DMTS), SPI, 30200 Bagnols-sur-Cèze, FranceImpedanCELL Platform, Federative Structure 4206 ICORE, NormandieUniv, UNICAEN, Inserm U1086 ANTICIPE, Biology and Innovative Therapeutics for Ovarian Cancers Group (BioTICLA), Comprehensive Cancer Center F. Baclesse, 14000 Caen, FranceUMR6252 CIMAP, Team Applications in Radiobiology with Accelerated Ions, CEA-CNRS-ENSICAEN-Université de Caen Normandie, 14000 Caen, FranceDepartment of Life and Environmental Physics, HoriaHulubei National Institute of Physics and Nuclear Engineering, 077125 Magurele, RomaniaUMR6252 CIMAP, Team Applications in Radiobiology with Accelerated Ions, CEA-CNRS-ENSICAEN-Université de Caen Normandie, 14000 Caen, FranceBesides the direct effects of radiations, indirect effects are observed within the surrounding non-irradiated area; irradiated cells relay stress signals in this close proximity, inducing the so-called radiation-induced bystander effect. These signals received by neighboring unirradiated cells induce specific responses similar with those of direct irradiated cells. To understand the cellular response of bystander cells, we performed a 2D gel-based proteomic study of the chondrocytes receiving the conditioned medium of low-dose irradiated chondrosarcoma cells. The conditioned medium was directly analyzed by mass spectrometry in order to identify candidate bystander factors involved in the signal transmission. The proteomic analysis of the bystander chondrocytes highlighted 20 proteins spots that were significantly modified at low dose, implicating several cellular mechanisms, such as oxidative stress responses, cellular motility, and exosomes pathways. In addition, the secretomic analysis revealed that the abundance of 40 proteins in the conditioned medium of 0.1 Gy irradiated chondrosarcoma cells was significantly modified, as compared with the conditioned medium of non-irradiated cells. A large cluster of proteins involved in stress granules and several proteins involved in the cellular response to DNA damage stimuli were increased in the 0.1 Gy condition. Several of these candidates and cellular mechanisms were confirmed by functional analysis, such as 8-oxodG quantification, western blot, and wound-healing migration tests. Taken together, these results shed new lights on the complexity of the radiation-induced bystander effects and the large variety of the cellular and molecular mechanisms involved, including the identification of a new potential actor, namely the stress granules.https://www.mdpi.com/1422-0067/22/15/7957chondrosarcomabystander signalingproteomic analysissecretomestress granules |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Mihaela Tudor Antoine Gilbert Charlotte Lepleux Mihaela Temelie Sonia Hem Jean Armengaud Emilie Brotin Siamak Haghdoost Diana Savu François Chevalier |
spellingShingle |
Mihaela Tudor Antoine Gilbert Charlotte Lepleux Mihaela Temelie Sonia Hem Jean Armengaud Emilie Brotin Siamak Haghdoost Diana Savu François Chevalier A Proteomic Study Suggests Stress Granules as New Potential Actors in Radiation-Induced Bystander Effects International Journal of Molecular Sciences chondrosarcoma bystander signaling proteomic analysis secretome stress granules |
author_facet |
Mihaela Tudor Antoine Gilbert Charlotte Lepleux Mihaela Temelie Sonia Hem Jean Armengaud Emilie Brotin Siamak Haghdoost Diana Savu François Chevalier |
author_sort |
Mihaela Tudor |
title |
A Proteomic Study Suggests Stress Granules as New Potential Actors in Radiation-Induced Bystander Effects |
title_short |
A Proteomic Study Suggests Stress Granules as New Potential Actors in Radiation-Induced Bystander Effects |
title_full |
A Proteomic Study Suggests Stress Granules as New Potential Actors in Radiation-Induced Bystander Effects |
title_fullStr |
A Proteomic Study Suggests Stress Granules as New Potential Actors in Radiation-Induced Bystander Effects |
title_full_unstemmed |
A Proteomic Study Suggests Stress Granules as New Potential Actors in Radiation-Induced Bystander Effects |
title_sort |
proteomic study suggests stress granules as new potential actors in radiation-induced bystander effects |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2021-07-01 |
description |
Besides the direct effects of radiations, indirect effects are observed within the surrounding non-irradiated area; irradiated cells relay stress signals in this close proximity, inducing the so-called radiation-induced bystander effect. These signals received by neighboring unirradiated cells induce specific responses similar with those of direct irradiated cells. To understand the cellular response of bystander cells, we performed a 2D gel-based proteomic study of the chondrocytes receiving the conditioned medium of low-dose irradiated chondrosarcoma cells. The conditioned medium was directly analyzed by mass spectrometry in order to identify candidate bystander factors involved in the signal transmission. The proteomic analysis of the bystander chondrocytes highlighted 20 proteins spots that were significantly modified at low dose, implicating several cellular mechanisms, such as oxidative stress responses, cellular motility, and exosomes pathways. In addition, the secretomic analysis revealed that the abundance of 40 proteins in the conditioned medium of 0.1 Gy irradiated chondrosarcoma cells was significantly modified, as compared with the conditioned medium of non-irradiated cells. A large cluster of proteins involved in stress granules and several proteins involved in the cellular response to DNA damage stimuli were increased in the 0.1 Gy condition. Several of these candidates and cellular mechanisms were confirmed by functional analysis, such as 8-oxodG quantification, western blot, and wound-healing migration tests. Taken together, these results shed new lights on the complexity of the radiation-induced bystander effects and the large variety of the cellular and molecular mechanisms involved, including the identification of a new potential actor, namely the stress granules. |
topic |
chondrosarcoma bystander signaling proteomic analysis secretome stress granules |
url |
https://www.mdpi.com/1422-0067/22/15/7957 |
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