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

Authors: Tudor, Mihaela; Gilbert, Antoine; Lepleux, Charlotte; Temelie, Mihaela; Hem, Sonia; Armengaud, Jean; Brotin, Emilie; +3 Authors

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.

Country
France
Keywords

Proteomics, stress granules, Chondrosarcoma, 610, [SDV.CAN]Life Sciences [q-bio]/Cancer, Bone Neoplasms, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Cytoplasmic Granules, Article, Chondrocytes, [SDV.CAN] Life Sciences [q-bio]/Cancer, bystander signaling, Cell Line, Tumor, Humans, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Molecular Biology/Genomics [q-bio.GN], chondrosarcoma, [PHYS.PHYS.PHYS-MED-PH] Physics [physics]/Physics [physics]/Medical Physics [physics.med-ph], X-Rays, Bystander Effect, proteomic analysis, secretome, [PHYS.PHYS.PHYS-MED-PH]Physics [physics]/Physics [physics]/Medical Physics [physics.med-ph], [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN]

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    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
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    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
9
Top 10%
Average
Top 10%
Green
gold