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A Proteomic Study Suggests Stress Granules as New Potential Actors in Radiation-Induced Bystander Effects

Abstract : 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.
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https://hal.archives-ouvertes.fr/hal-03301338
Contributor : Francois Chevalier Connect in order to contact the contributor
Submitted on : Tuesday, July 27, 2021 - 4:39:10 PM
Last modification on : Saturday, June 25, 2022 - 9:56:47 AM
Long-term archiving on: : Thursday, October 28, 2021 - 6:35:44 PM

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Mihaela Tudor, Antoine Gilbert, Charlotte Lepleux, Mihaela Temelie, Sonia Hem, et al.. A Proteomic Study Suggests Stress Granules as New Potential Actors in Radiation-Induced Bystander Effects. International Journal of Molecular Sciences, MDPI, 2021, 22 (15), pp.7957. ⟨10.3390/ijms22157957⟩. ⟨hal-03301338⟩

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