Oxidized DNA induces an adaptive response in human fibroblasts

Kostyuk, Svetlana V.; Tabakov, V. J.; Chestkov, Valerij V.; Konkova, Marina S.; Glebova, K. V.; Baydakova, Galina; Ershova, Elizaveta S.; Ижевская, В. Л.; Baranova, Ancha; Veiko, Natalia N.

doi:10.1016/j.mrfmmm.2013.04.007

Cited by 26 publications

(35 citation statements)

References 58 publications

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“…Compound F-828 is well soluble in water and culture medium in the presence as well as in the absence of serum. We used F-828 in concentrations ranging from 0.1 to 2.0 µ M for the analysis of its effects on proliferation of HELFs under the conditions of chronic oxidative stress induced by serum deprivation (the model elaborated and reported previously [17]). The fullerene derivative was added to the medium at the initial stage of HELF cultivation, which was as long as 48 hours.…”

Section: Resultsmentioning

confidence: 99%

“…Cultivation of HELFs in a serum-starving medium is known to result in a notable increase in the ROS level (Figure 6(a) and [17]). To study the possible influence of the fullerene on the intracellular ROS levels, the ROS were measured using dichlorodihydrofluorescein diacetate (H2DCFH-DA) dye.…”

Section: Resultsmentioning

confidence: 99%

“…NRF2 factor is expressed in serum-starving HELFs at the same level as in the cells growing in the presence of 2% of serum. However, this factor is not active and it is localized only in cytoplasm of the serum-starving HELFs [17]. In the cells cultivated in presence of serum NRF2 is located in the nucleus.…”

Section: Resultsmentioning

confidence: 99%

“…It was previously shown that serum-free cultivation elicits chronic stress due to increased production of ROS as compared to the serum-supplemented cultures [17]. The increase in the production of free radicals is accompanied by an increase in the population of cells with numerous DSBs.…”

Section: Introductionmentioning

confidence: 99%

“…We also observed an increase in the number of cells with condensed and fragmented chromatin due to cultivation in the absence of serum, which is an indicator of ongoing apoptosis. In the stressed, serum-starving fibroblasts, the level and activity of the transcriptional factor NF- κ B increase along with elevation of secreted concentrations of TNF α cytokine, while the NRF2 activity decreases [17]. Thus, serum-starving HELFs represent a good model to study water-soluble fullerene-mediated NRF2 induction and NF- κ B activity repression under the conditions of chronic oxidative stress, which provokes double-strand break formation in the cells.…”

Section: Introductionmentioning

confidence: 99%

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Functionalized Fullerene Increases NF‐κB Activity and Blocks Genotoxic Effect of Oxidative Stress in Serum‐Starving Human Embryo Lung Diploid Fibroblasts

Ershova

Sergeeva

Tabakov

et al. 2016

Oxidative Medicine and Cellular Longevity

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The influence of a water-soluble [60] fullerene derivative containing five residues of 3-phenylpropionic acid and a chlorine addend appended to the carbon cage (F-828) on serum-starving human embryo lung diploid fibroblasts (HELFs) was studied. Serum deprivation evokes oxidative stress in HELFs. Cultivation of serum-starving HELFs in the presence of 0.1–1 µM F-828 significantly decreases the level of free radicals, inhibits autophagy, and represses expression of NOX4 and NRF2 proteins. The activity of NF-κB substantially grows up in contrast to the suppressed NRF2 activity. In the presence of 0.2–0.25 µM F-828, the DSB rate and apoptosis level dramatically decrease. The maximum increase of proliferative activity of the HELFs and maximum activity of NF-κB are observed at these concentration values. Conclusion. Under the conditions of oxidative stress evoked by serum deprivation the water-soluble fullerene derivative F-828 used in concentrations of 0.1 to 1 µM strongly stimulates the NF-κB activity and represses the NRF2 activity in HELFs.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Functionalized Fullerene Increases NF‐κB Activity and Blocks Genotoxic Effect of Oxidative Stress in Serum‐Starving Human Embryo Lung Diploid Fibroblasts

Ershova

Sergeeva

Tabakov

et al. 2016

Oxidative Medicine and Cellular Longevity

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

Sergeeva¹,

Kostyuk²,

Ershova³

et al. 2016

Advances in Experimental Medicine and Biology

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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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Sessile Innate Immune Cells

Land

2018

Damage-Associated Molecular Patterns in Human Diseases

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Oxidized DNA induces an adaptive response in human fibroblasts

Cited by 26 publications

References 58 publications

Functionalized Fullerene Increases NF‐κB Activity and Blocks Genotoxic Effect of Oxidative Stress in Serum‐Starving Human Embryo Lung Diploid Fibroblasts

Functionalized Fullerene Increases NF‐κB Activity and Blocks Genotoxic Effect of Oxidative Stress in Serum‐Starving Human Embryo Lung Diploid Fibroblasts

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

Sessile Innate Immune Cells

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