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GC-Rich DNA Fragments and Oxidized Cell-Free DNA Have Different Effects on NF-kB and NRF2 Signaling in MSC

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Circulating Nucleic Acids in Serum and Plasma – CNAPS IX

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.

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References

  • Dominici M, Le Blanc K, Mueller I et al (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The international society for cellular therapy position statement. Cytotherapy 8(4):315–317

    Article  CAS  PubMed  Google Scholar 

  • Ermakov A, Konkova M, Kostyuk S et al (2013) Oxidized extracellular DNA as a stress signal in human cells. Oxid Med Cell Longev 2013:649747

    Article  PubMed  PubMed Central  Google Scholar 

  • Kostyuk S, Loseva P, Chvartatskaya O et al (2012) Extracellular GC-rich DNA activates TLR9- and NF-kB-dependent signaling pathways in human adipose-derived mesenchymal stem cells (haMSCs). Expert Opin Biol Ther 12(Suppl 1):99–111

    Article  Google Scholar 

  • Kostyuk S, Tabakov V, Chestkov V et al (2013) Oxidized DNA induces an adaptive response in human fibroblasts. Mutat Res 747–748:6–18

    Article  PubMed  Google Scholar 

  • Lau A, Villeneuve NF, Sun Z et al (2008) Dual roles of Nrf2 in cancer. Pharmacol Res 58(5–6):262–270

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu GH, Qu J, Shen X (2008) NF-kappaB/p65 antagonizes Nrf2-ARE pathway by depriving CBP from Nrf2 and facilitating recruitment of HDAC3 to MafK. Biochim Biophys Acta 1783(5):713–727

    Article  CAS  PubMed  Google Scholar 

  • Loseva P, Kostyuk S, Malinovskaya E et al (2012) Extracellular DNA oxidation stimulates activation of NRF2 and reduces the production of ROS in human mesenchymal stem cells. Expert Opin Biol Ther 12(Suppl 1):85–97

    Article  Google Scholar 

  • Nair S, Doh ST, Chan JY et al (2008) Regulatory potential for concerted modulation of Nrf2- and Nfkb1-mediated gene expression in inflammation and carcinogenesis. Br J Cancer 99(12):2070–2082

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nguyen T, Huang HC, Pickett CB (2000) Transcriptional regulation of the antioxidant response element. Activation by Nrf2 and repression by MafK. J Biol Chem 275(20):15466–15473

    Article  CAS  PubMed  Google Scholar 

  • Pedruzzi LM, Stockler-Pinto MB, Leite M Jr et al (2012) Nrf2-keap1 system versus NF-kB: the good and the evil in chronic kidney disease? Biochimie 94(12):2461–2466

    Article  CAS  PubMed  Google Scholar 

  • Wakabayashi N, Slocum SL, Skoko JJ et al (2010) When NRF2 talks, who’s listening? Antioxid Redox Signal 13(11):1649–1663

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Conflict of Interest

Sergeeva V.A., Kostyuk S.V., Ershova E.S., Smirnova T.D., Kameneva L.V., Veiko N.N. state that there are no conflicts of interest.

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Correspondence to Vasilina A. Sergeeva .

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Sergeeva, V.A. et al. (2016). GC-Rich DNA Fragments and Oxidized Cell-Free DNA Have Different Effects on NF-kB and NRF2 Signaling in MSC. In: Gahan, P., Fleischhacker, M., Schmidt, B. (eds) Circulating Nucleic Acids in Serum and Plasma – CNAPS IX. Advances in Experimental Medicine and Biology, vol 924. Springer, Cham. https://doi.org/10.1007/978-3-319-42044-8_21

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