Ribosomal repeat in cell free DNA as a marker for cell death

Вейко, Н. Н.; Bulycheva, N. A.; Roginko, O.; Veiko, Roman V.; Ershova, Elizaveta S.; Kozdoba, O. A.; Kuzmin, V.; Vinogradov, A.; Yudin, A. A.; Speranskyi, A. I.

doi:10.1134/s1990750808020121

Cited by 24 publications

(34 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These concentrations increase with age or in presence of various stressful conditions, for example, pregnancy, intensive exercise, or strong emotions as well as when malignancy or other chronic pathology is diagnosed. In plasma samples of patients with cancer or critical cardiovascular conditions, the concentrations of cfDNA increase up to 1000 ng/mL [84–92]. …”

Section: Extracellular Dna Is Enriched With the Oxidized Genomic Dnamentioning

confidence: 99%

“…In addition to preferential enrichment of cfDNA pools with oxidized DNA of dying cells, the contents of 8-oxodG in cfDNA may depend on well-known phenomenon of somewhat slowed down degradation of GC-rich DNA fragments in human serum as compared to AT-rich fragments [21, 92, 104–106]. Moreover, under the condition of oxidative stress, an increase in proportions of mitochondrial DNA within cfDNA was documented [80–82].…”

Section: Extracellular Dna Is Enriched With the Oxidized Genomic Dnamentioning

confidence: 99%

See 1 more Smart Citation

Oxidized Extracellular DNA as a Stress Signal in Human Cells

Ermakov

Konkova

Kostyuk

et al. 2013

Oxidative Medicine and Cellular Longevity

114

122

View full text Add to dashboard Cite

The 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.

show abstract

Section: Extracellular Dna Is Enriched With the Oxidized Genomic Dnamentioning

confidence: 99%

Section: Extracellular Dna Is Enriched With the Oxidized Genomic Dnamentioning

confidence: 99%

Oxidized Extracellular DNA as a Stress Signal in Human Cells

Ermakov

Konkova

Kostyuk

et al. 2013

Oxidative Medicine and Cellular Longevity

114

122

View full text Add to dashboard Cite

show abstract

“…Our previous studies showed that the concentration of ecDNA in the blood increases during cardiovascular diseases. These changes are accompanied by an increase in the amount of CG-rich repeats in ecDNA (CG-DNA) [1]. Since vascular endothelial cells produce protein receptors (TLR9) for CG-DNA, it can be hypothesized that endogenous DNA fragments activate the intracellular signal pathway associated with activation of the expression of TLR9 gene and adapter protein MyD88 [9].…”

mentioning

confidence: 99%

Enhanced Expression of iNOS in Human Endothelial Cells during Long-Term Culturing with Extracellular DNA Fragments

et al. 2010

Self Cite

View full text Add to dashboard Cite

NO synthesis by endothelial cells plays an important role in normal function of the cardiovascular system. This work was designed to evaluate the role of variations in properties of extracellular DNA in the regulation of NO synthesis. We studied the effect of four DNA samples with various base sequences (50 ng/ml) on functional activity of endothelial cells HUVEC during 24-h culturing. Human DNA fragments with high content of CG repeats increased intracellular content of NO and its metabolites (nitrites and nitrates) and accelerated oxidation of nitrites to nitrates. Changes in the content of NO metabolites after 24-h culturing was shown to depend on the expression of gene for inducible, but not for endothelial NO synthase. Increased expression of inducible NO synthase positively correlated with an increase in the content of mRNA for the adapter protein MyD88, but did not depend on TLR9 gene expression that encodes protein receptor for CG-DNA recognition. The intracellular concentration of MyD88 mRNA did not depend on the content of TLR9 mRNA. The existence of a variety of DNA-binding receptors apart from TLR9 receptor on the surface of endothelial cells was hypothesized. Activation of these receptors by extracellular DNA fragments stimulates expression of the adapter protein MyD88.Extracellular DNA (ecDNA) has attracted much interest over the past decade. ecDNA circulates in the blood and other biological fl uids of the organism. The properties of ecDNA are modifi ed under pathological conditions [11]. Our previous studies showed that the concentration of ecDNA in the blood increases during cardiovascular diseases. These changes are accompanied by an increase in the amount of CG-rich repeats in ecDNA (CG-DNA) [1]. Since vascular endothelial cells produce protein receptors (TLR9) for CG-DNA, it can be hypothesized that endogenous DNA fragments activate the intracellular signal pathway associated with activation of the expression of TLR9 gene and adapter protein MyD88 [9]. Binding of CG-DNA to TLR9 results in the synthesis of cellular cytokines, reactive oxygen species, and nitrogen [10]. TLR9 activation in some cells is accompanied by stimulation of NO synthesis due to an increase in the expression of inducible NO synthase (iNOS) [7]. It was hypothesized that functional activity of TLR receptors plays a role in the development of atherosclerosis [5].This work was designed to evaluate whether the properties of ecDNA (e.g., variations in CG-DNA content) may affect the endothelial function via activation of TLR9 expression. We studied the long-term effect

show abstract

“…30.2). These two characteristics are interrelated (Veiko et al 2008). The value of lg(MCG) decreases with an increase in C tot for cfDNA in PAMI (k = -0.83, p = 0.003, n = 10).…”

Section: Resultsmentioning

confidence: 89%

Cell Free DNA (cfDNA) Influences Nitric Oxide and ros Levels in Human Endothelial Cells

Alekseeva

Bulycheva

Kostyuk

et al. 2010

Circulating Nucleic Acids in Plasma and Serum

View full text Add to dashboard Cite

Various samples of cfDNA added to endothelial cell cultures resulted in a number of effects. cfDNA in concentrations similar to those in human blood plasma caused an increase in NO synthesis in endothelial cells. In addition, cfDNA isolated from blood from patients with cardiovascular diseases influenced ROS synthesis more efficiently than cfDNA from healthy donors. Also, the ability of cfDNA to influence the elaboration of NO and ROS depends on the sample concentration and the content of CG-DNA marker.

show abstract

Ribosomal repeat in cell free DNA as a marker for cell death

Cited by 24 publications

References 11 publications

Oxidized Extracellular DNA as a Stress Signal in Human Cells

Oxidized Extracellular DNA as a Stress Signal in Human Cells

Enhanced Expression of iNOS in Human Endothelial Cells during Long-Term Culturing with Extracellular DNA Fragments

Cell Free DNA (cfDNA) Influences Nitric Oxide and ros Levels in Human Endothelial Cells

Contact Info

Product

Resources

About