Oxidized Extracellular DNA as a Stress Signal in Human Cells

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dc.contributor.authorErmakov, Aleksei V.
dc.contributor.authorKonkova, Marina S.
dc.contributor.authorKostyuk, Svetlana V.
dc.contributor.authorIzevskaya, Vera L.
dc.contributor.authorBaranova, Ancha
dc.contributor.authorVeiko, Natalya N.
dc.date.accessioned2014-09-12T23:46:28Z
dc.date.available2014-09-12T23:46:28Z
dc.date.issued2013-01
dc.description.abstractThe term “cell-free DNA” (cfDNA) was recently coined for DNA fragments from plasma/serum, while DNA present in in vitro cell culture media is known as extracellular DNA (ecDNA). Under oxidative stress conditions, the levels of oxidative modification of cellular DNA and the rate of cell death increase. Dying cells release their damaged DNA, thus, contributing oxidized DNA fragments to the pool of cfDNA/ecDNA. Oxidized cell-free DNA could serve as a stress signal that promotes irradiation-induced bystander effect. Evidence points to TLR9 as a possible candidate for oxidized DNA sensor. An exposure to oxidized ecDNA stimulates a synthesis of reactive oxygen species (ROS) that evokes an adaptive response that includes transposition of the homologous loci within the nucleus, polymerization and the formation of the stress fibers of the actin, as well as activation of the ribosomal gene expression, and nuclear translocation of NF-E2 related factor-2 (NRF2) that, in turn, mediates induction of phase II detoxifying and antioxidant enzymes. In conclusion, the oxidized DNA is a stress signal released in response to oxidative stress in the cultured cells and, possibly, in the human body; in particular, it might contribute to systemic abscopal effects of localized irradiation treatments.
dc.description.sponsorshipThis work was supported by the RFBR (12-04-32081), by the Contract no. 8273 (August 27, 2012) under the call no. 2012-1.1-12-000-2008-067 of the Ministry of Education and Science of Russia, and by Thomas F. Jeffress and Kate Miller Jeffress Foundation Grant J-1023.
dc.identifier.citationAleksei V. Ermakov, Marina S. Konkova, Svetlana V. Kostyuk, Vera L. Izevskaya, Ancha Baranova, and Natalya N. Veiko, “Oxidized Extracellular DNA as a Stress Signal in Human Cells,” Oxidative Medicine and Cellular Longevity, vol. 2013, Article ID 649747, 12 pages, 2013. doi:10.1155/2013/649747
dc.identifier.otherdoi:10.1155/2013/649747
dc.identifier.urihttps://hdl.handle.net/1920/8814
dc.language.isoen_US
dc.publisherHindawi Publishing Corporation
dc.rightsAttribution 3.0 United States
dc.rights.urihttps://creativecommons.org/licenses/by/3.0/us/
dc.subjectAdaptive responses
dc.subjectBystander effect
dc.subjectDNA double-strand breaks
dc.subjectExtracellular DNA
dc.subjectOxidative stress
dc.subjectReactive oxygen species
dc.subjectHuman umbilical vein endothelial cells
dc.subjectMesenchymal stem cells.
dc.titleOxidized Extracellular DNA as a Stress Signal in Human Cells
dc.typeArticle

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