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

Adv Exp Med Biol. 2016:924:109-112. doi: 10.1007/978-3-319-42044-8_21.

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.

Keywords: Cell-free DNA; GC-rich cell-free DNA; MSCs; Oxidized cell-free DNA.

MeSH terms

  • Cells, Cultured
  • DNA / genetics*
  • DNA / metabolism
  • GC Rich Sequence*
  • Gene Expression
  • Humans
  • Mesenchymal Stem Cells / metabolism*
  • NF-E2-Related Factor 2 / genetics*
  • NF-E2-Related Factor 2 / metabolism
  • NF-kappa B / genetics*
  • NF-kappa B / metabolism
  • Oxidation-Reduction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / genetics*
  • Time Factors

Substances

  • NF-E2-Related Factor 2
  • NF-kappa B
  • NFE2L2 protein, human
  • DNA