Mitochondrial and Nuclear DNA in Patients with Severe Polytrauma

Хубутия, М. Ш.; Шабанов, А. К.; Скулачев, М. В.; Bulava, G. V.; Савченко, І.М.; Гребенников, О. А.; Сергеев, А А; Zorov, Dmitry B.; Zinovkin, Roman A.

doi:10.15360/1813-9779-2013-6-24

Cited by 13 publications

(12 citation statements)

References 18 publications

(12 reference statements)

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“…1b), consis tent with other studies [4,8]. However, it remains unclear whether mtDNA participates in the life threatening excessive activation of innate immunity, or just represents a marker of cell injury.…”

Section: Discussionsupporting

confidence: 69%

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Pure mitochondrial DNA does not activate human neutrophils in vitro

Prikhodko

Шабанов

Zinovkina

et al. 2015

Biochemistry Moscow

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Excessive activation of the innate immune system often leads to fatal consequences and can be considered as one of the phenoptotic events. After traumatic injury, various components of mitochondria are released into the circulation and stimulate myeloid cells of the innate immunity. Presumably, mitochondrial DNA (mtDNA) might activate immune cells (Zhang, Q., et al. (2010) Nature, 464, 104-107). In the present study, we investigated the role of mtDNA as a direct activator of human neutrophils, as well as a prognostic marker in patients with severe trauma. Quantitative determination of mtDNA in the plasma of these patients revealed its significant increase (p < 0.02) in the group of survivors compared to non-survivors. Highly purified mtDNA was not able to induce activation of human neutrophils, thus possibly indicating the existence of additional factor(s) ensuring the recognition of mtDNA as a damage-associated molecular pattern.

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Section: Discussionsupporting

confidence: 69%

“…PCR efficiency was calculated using serial dilutions of total DNA from HeLa cells (NEB, England) or control plasmid DNA from 10 μg/ml to 1 pg/ml. The results were normalized accord ing to the amplification of control plasmid DNA [8].…”

Section: Methodsmentioning

confidence: 99%

Pure mitochondrial DNA does not activate human neutrophils in vitro

Prikhodko

Шабанов

Zinovkina

et al. 2015

Biochemistry Moscow

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“…An increase in cfDNA concentration occurs under both physiological and pathological conditions [5][6][7][8][9]. We assume that cfDNA has a beneficial or damaging effect depending on the duration of its increased concentration.…”

Section: Discussionmentioning

confidence: 99%

“…An imbalance between death, birth, and differentiation may contribute to various neuropathologies [3,4]. It has been found that in chronic stress, neurodegenerative diseases, traumatic brain injury, sepsis, and stroke, the increased cell-free DNA (cfDNA) concentration in plasma is associated with the course and/or outcome [5][6][7][8][9]. Oxidative stress after cerebral ischemia is shown to induce DNA damage in the brain [10].…”

Section: Introductionmentioning

confidence: 99%

Oxidized Cell-Free DNA Rapidly Skews the Transcriptional Profile of Brain Cells toward Boosting Neurogenesis and Neuroplasticity

Filev

Kostyuk

Umriukhin

et al. 2021

CIMB

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Cell-free DNA (cfDNA) is liberated and accumulated in neural tissue due to cell damage. The oxidative and nitrosative stress in the brain that accompanies various pathological conditions has been shown to increase the oxidation of cellular and cell-free DNA. Whether the high concentration of non-oxidized and oxidized cfDNA may affect the transcriptome response of brain cells has not been studied. In the current work, we studied whether cfDNA fragments affect several key pathways, including neurogenesis, at the level of gene expression in brain cells. In the study, primary rat cerebellum cell cultures were used to assess the effects of oxidized and non-oxidized cfDNA on the expression of 91 genes in brain cells. We found that only oxidized cfDNA, not non-oxidized cfDNA, significantly altered the transcription in brain cells in 3 h. The pattern of change included all 10 upregulated genes (S100A8, S100A9, S100b, TrkB, Ngf, Pink1, Aqp4, Nmdar, Kcnk2, Mapk1) belonging to genes associated with neurogenesis and neuroplasticity. The expression of inflammatory and apoptosis genes, which oppose neurogenesis, decreased. The results show that the oxidized form of cfDNA positively regulates early gene expression of neurogenesis and neuroplasticity. At the same time, the question of whether chronic elevation of cfDNA concentration alters brain cells remains unexplored.

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“…Также было установлено повышенное содержание яДНК в крови в результате повреждения обширных массивов тканей при тяжелой сочетанной травме (ТСТ) [1]. На сегодняшний день именно эта модель (ТСТ) представляется наиболее изученной, опубликован систематический обзор 14 обсервационных исследований, посвященных изучению уровня внеклеточной ДНК и исходов у больных с ТСТ.…”

Section: заключениеunclassified

Evaluation of nuclear DNA level in plasma of cardiac-surgery patients as a predictor of multiorgan dysfunction

Гребенчиков

Скрипкин

Забелина

et al. 2018

Regional blood circulation and microcirculation

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The purpose of the study: to assess the significance of the nDNA plasma level in patients after cardiac surgery to predict the development of acute heart failure (AHF), acute kidney injury (AKI) and SIRS. Material and methods. The present prospective observational pilot cohort study of nDNA plasma level and the development of complications. Results. The nDNA plasma level was maximal 12 h after surgery. The level of nDNA > 20.5 ng/ml 12 h after surgery can predict risk of SIRS (sensitivity/specificity - 56/75 %); > 17.9 ng/ml - risk of AKI (79/69 %) and the AHF (62/58 %). Conclusion. The nDNA plasma level may be a predictor of early complications after cardiac surgery.

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Mitochondrial and Nuclear DNA in Patients with Severe Polytrauma

Cited by 13 publications

References 18 publications

Pure mitochondrial DNA does not activate human neutrophils in vitro

Pure mitochondrial DNA does not activate human neutrophils in vitro

Oxidized Cell-Free DNA Rapidly Skews the Transcriptional Profile of Brain Cells toward Boosting Neurogenesis and Neuroplasticity

Evaluation of nuclear DNA level in plasma of cardiac-surgery patients as a predictor of multiorgan dysfunction

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