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PXD032143

PXD032143 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleRadiation-induced bystander effect mediated by exosomes involves the replication stress in recipient cells.
DescriptionExosomes released by irradiated cells mediate radiation-induced bystander effect, which is manifested by DNA breaks detected in recipient cells, yet the specific mechanism responsible for generation of chromosome lesions remains unclear. In this study, naïve FaDu head and neck cancer cells were stimulated with exosomes released by irradiated (a single 2Gy dose) or mock-irradiated cells. Maximum accumulation of gamma H2A.X foci, a marker of DNA breaks, was detected after one hour of stimulation with exosomes from irradiated donors, the level of which was comparable to the one observed in directly irradiated cells (a weaker wave of the gamma H2A.X foci accumulation was also noted after 23 hours of stimulation). Exosomes from irradiated cells, but not from control ones, activated two stress-induced protein kinases: ATM and ATR. Noteworthy, while direct irradiation activated only ATM, both ATM and ATR were activated by two factors known to induce the replication stress: hydroxyurea and camptothecin (with subsequent phosphorylation of gamma H2A.X). One hour of stimulation with exosomes from irradiated cells suppressed DNA synthesis in recipient cells and resulted in the subsequent nuclear accumulation of RNA:DNA hybrids, which is an indicator of impaired replication. Interestingly, the abovementioned effects were observed before a substantial internalization of exosomes, which may suggest a receptor-mediated mechanism. After one hour of stimulation with exosomes from irradiated donors increased phosphorylation of several nuclear proteins was observed, including replication factors and regulators of heterochromatin remodeling, as well as components of multiple intracellular signaling pathways. Hence, we concluded that the bystander effect mediated by exosomes released from irradiated cells involves the replication stress in recipient cells.
HostingRepositoryPRIDE
AnnounceDate2022-05-20
AnnouncementXMLSubmission_2022-05-20_08:10:18.099.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterMonika Pietrowska
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListphosphorylated residue
InstrumentQ Exactive Plus
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-03-09 02:05:36ID requested
12022-05-20 08:10:19announced
Publication List
Smolarz M, Skoczylas Ł, Gawin M, Krzy, ż, owska M, Pietrowska M, Wid, ł, ak P, Radiation-Induced Bystander Effect Mediated by Exosomes Involves the Replication Stress in Recipient Cells. Int J Mol Sci, 23(8):(2022) [pubmed]
Keyword List
submitter keyword: bystander effect
exosomes
ionizing radiation
non-targeted effects of radiation
replication stress
Contact List
Piotr Widlak
contact affiliationMaria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch
contact emailpiotr.widlak@io.gliwice.pl
lab head
Monika Pietrowska
contact affiliationMaria Sklodowska-Curie National Research Institute of Oncology
contact emailmonika.pietrowska@io.gliwice.pl
dataset submitter
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