title: GC-Rich DNA Fragments and Oxidized Cell-Free DNA Have Different Effects on NF-kB and NRF2 Signaling in MSC.
abstract: It has been established that cell-free DNA circulating in the bloodstream affects cells. The characteristics of cfDNA depend on the physiological state of the organism. As we showed previously, diseases can cause either GC-enrichment of the cell-free DNA pool or its oxidation. Thus, in cases of cerebral atherosclerosis, heart attack and rheumatic arthritis the cell-free DNA pool is GC-enriched and, in the case of cancer, both GC-enriched and oxidized. Herein we investigated the time-dependent effect of oxidized and GC-rich cell-free DNA on NF-kB and NRF2 signaling pathways in human mesenchymal stem cells and showed that they affect cells in different ways. Oxidized DNA drastically increases expression of NRF2 in a short period of time, but the effect does not last long. GC-rich DNA causes a prolonged increase in mRNA levels of NF-kB and NRF2 which lasts 48 and 24 h, respectively.
authors.affiliation: "Research Centre for Medical Genetics", Federal State Budgetary Institution, Moskvorechie str., 1, Moscow, 115478, Russia. tracytheplane@gmail.com.
authors.forename: Vasilina A
authors.initials: VA
authors.lastname: Sergeeva
authors.affiliation: "Research Centre for Medical Genetics", Federal State Budgetary Institution, Moskvorechie str., 1, Moscow, 115478, Russia.
authors.forename: Svetlana V
authors.initials: SV
authors.lastname: Kostyuk
authors.affiliation: "Research Centre for Medical Genetics", Federal State Budgetary Institution, Moskvorechie str., 1, Moscow, 115478, Russia.
authors.forename: Elizaveta S
authors.initials: ES
authors.lastname: Ershova
authors.affiliation: "Research Centre for Medical Genetics", Federal State Budgetary Institution, Moskvorechie str., 1, Moscow, 115478, Russia.
authors.forename: Elena M
authors.initials: EM
authors.lastname: Malinovskaya
authors.affiliation: "Research Centre for Medical Genetics", Federal State Budgetary Institution, Moskvorechie str., 1, Moscow, 115478, Russia.
authors.forename: Tatiana D
authors.initials: TD
authors.lastname: Smirnova
authors.affiliation: "Research Centre for Medical Genetics", Federal State Budgetary Institution, Moskvorechie str., 1, Moscow, 115478, Russia.
authors.forename: Larisa V
authors.initials: LV
authors.lastname: Kameneva
authors.affiliation: "Research Centre for Medical Genetics", Federal State Budgetary Institution, Moskvorechie str., 1, Moscow, 115478, Russia.
authors.forename: Natalia N
authors.initials: NN
authors.lastname: Veiko
mesh_terms: D002478:Cells, Cultured; D004247:DNA / Q000235:genetics* / Q000378:metabolism; D020862:GC Rich Sequence; D015870:Gene Expression; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051267:NF-E2-Related Factor 2 / Q000235:genetics* / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism; D010084:Oxidation-Reduction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics*; D013997:Time Factors
chemical_list: D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; C495635:NFE2L2 protein, human; D004247:DNA
keywords: Cell-free DNA; GC-rich cell-free DNA; MSCs; Oxidized cell-free DNA