Extracellular DNA oxidation stimulates activation of NRF2 and reduces the production of ROS in human mesenchymal stem cells

Loseva, Polina; Kostyuk, Svetlana V.; Malinovskaya, Elena M.; Clément, Noémie; Dechesne, CA; Dani, Christian; Смирнова, Т. Д.; Glebova, K. V.; Байдакова, Г. В.; Baranova, Ancha; Ижевская, В. Л.; Гинтер, Е. К.; Вейко, Н. Н.

doi:10.1517/14712598.2012.688948

Cited by 37 publications

(47 citation statements)

References 28 publications

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“…Biochemical experiments indicated that knockdown of NRF2 could increase MDA concentration and decrease concentration of SOD, GSH and CAT, enhancing the effects of laminarin in MRC-5 cells. Numerous studies have proved the protective role of NRF2 against oxidation in various cell types, keratinocytes ( Madduma Hewage et al, 2016 ; Zheng et al, 2014 ), pancreatic β-cells ( Dinić et al, 2016 ), mesenchymal stem cells ( Loseva et al, 2012 ), amongst others, elevating SOD, GSH and CAT cellular concentration. Besides, up-regulation of NRF2 was accompanied with suppressed MDA level during the amelioration of oxidative damage ( Xie et al, 2014 ).…”

Section: Discussionmentioning

confidence: 99%

Laminarin protects against hydrogen peroxide-induced oxidative damage in MRC-5 cells possibly via regulating NRF2

Lü

Liu

Zhai

et al. 2017

PeerJ

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Oxidative damage is a major cause of lung diseases, including pulmonary fibrosis. Laminarin is a kind of polysaccharide extracted from brown algae and plays vital roles in various biological processes. However, the functions and mechanisms of laminarin in pulmonary oxidative damage are poorly understood. This study aimed at investigating the protective effect of laminarin against pulmonary oxidative damage and underlying mechanisms. Human lung fibroblasts MRC-5 cells were treated with hydrogen peroxide to induce oxidative damage. Laminarin treatment was performed before or after hydrogen peroxide treatment, and then major indexes of oxidative damage, including superoxide dismutase (SOD), malondialdehyde (MDA), reduced glutathione (GSH) and catalase (CAT), were quantified by biochemical assays. The expression of oxidation-related factor, nuclear factor erythroid 2 like 2 (NRF2) was analyzed by qPCR, Western blot and immunofluorescence assay. NRF2 knockdown and overexpression were performed by cell transfection to reveal possible mechanisms. Results showed that laminarin treatment of 0.020 mg/mL for 24 h, especially the pre-treatment, could significantly relieve changes in SOD, MDA, GSH and CAT that were altered by hydrogen peroxide, and promote NRF2 mRNA (P < 0.001). NRF2 protein was also elevated by laminarin, and nuclear translocation was observed. Factors in NRF2 signaling pathways, including KEAP1, NQO1, GCLC and HO1, were all regulated by laminarin. Roles of NRF2 were tested, suggesting that NRF2 regulated the concentration of SOD, MDA, GSH and CAT, suppressed KEAP1, and promoted NQO1, GCLC and HO1. These findings suggested the protective role of laminarin against pulmonary oxidative damage, which might involve the regulation of NRF2 signaling pathways. This study provided information for the clinical application of laminarin to pulmonary diseases like pulmonary fibrosis.

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Section: Discussionmentioning

confidence: 99%

Laminarin protects against hydrogen peroxide-induced oxidative damage in MRC-5 cells possibly via regulating NRF2

Lü

Liu

Zhai

et al. 2017

PeerJ

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“…The degrees of enrichment were significant when cfDNA/ecDNA and cellular DNA samples were evaluated for cancer or myocardial infarction patients, for primary tumor cells, as well as for endotheliocytes cultures that were irradiated or treated with peroxide [30, 33]. …”

Section: Extracellular Dna Is Enriched With the Oxidized Genomic Dnamentioning

confidence: 99%

“…The cfDNA from ischemic rats decreased the levels of ROS production in neuronal cultures [32]. Both ecDNA collected from the media of primary tumor cells cultures and cfDNA extracted from plasma of cancer patients have influenced ROS production in mesenchymal stem cells (MSCs) [33]. Importantly, cfDNAs extracted from blood of myocardial infarction and rheumatoid arthritis patients stimulate the expression of DNA sensor toll-like receptor 9 (TLR9) in MSCs, while an exposure to gDNA did not influence TLR9 levels [35].…”

Section: Oxidized Cfdna/ecdna Is a Stress Signalmentioning

confidence: 99%

“…In endothelial cells, exposure to gDNA OX stimulated an expression of NOX4 and suppresses eNOS , therefore, augmenting net production of ROS and decreasing the levels of NO [34]. In mesenchymal stem cells, increased concentrations of gDNA OX and oxidized cfDNA/ecDNA stimulated a rapid increase in ROS synthesis and upregulated expression levels of the NF-E2-related factor-2 (NRF2), that plays a central role in antioxidant-response-element- (ARE-) mediated induction of phase II detoxifying and antioxidant enzymes along with a number of antioxidant response genes [33]. …”

Section: Oxidized Cfdna/ecdna Is a Stress Signalmentioning

confidence: 99%

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Oxidized Extracellular DNA as a Stress Signal in Human Cells

Ermakov

Konkova

Kostyuk

et al. 2013

Oxidative Medicine and Cellular Longevity

106

113

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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.

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“…Великий інтерес представляє фізіологічна методика визначення рівня стресу, яка виходить із того, що молекулярну основу стресу становлять активні форми кисню. Це високореактівні сполуки, які ушкоджують клітинні макромолекули -білки і ДНК [8]. Стрес пропорційний рівню активних форм кисню, який може збільшуватися або знижуватися в залежності від загального стану клітини.…”

unclassified

Effects of Stress on the Results of Economic Activity of Business Entities

Kryshtal¹,

Obelets²

2019

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Національний технічний університет України «Київський політехнічний інститут імені Ігоря Сікорського» ВПЛИВ СТРЕСУ НА РЕЗУЛЬТАТИ ЕКОНОМІЧНОЇ ДІЯЛЬНОСТІ СУБ'ЄКТІВ ГОСПОДАРЮВАННЯ Анотація. Розглянуто питання розповсюдженості стресу, його значний негативний вплив на економічні показники в різних країнах, і, внаслідок цього, необхідність його врахування для оцінки продуктивності і витрат. Запропоновано психологічні і фізіологічні методи, які можна застосовувати для визначення рівня стресу. Досліджена можливість використання штучних нейронних мереж для аналізу продуктивності праці з урахуванням рівня стресу. Проблема аналізу впливу стресу на різні економічні показники повинна вирішуватися на всіх рівнях управління: від підприємства до державного. Вона є наукомісткою і потребує значних вкладень, але результати досліджень дозволять знайти шляхи для зменшення негативного ефекту стресу на економіку. Ключові слова: стрес, продуктивність праці, нейронні мережі.

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Extracellular DNA oxidation stimulates activation of NRF2 and reduces the production of ROS in human mesenchymal stem cells

Abstract: Oxidized cfDNA up-regulates NRF2 and PPARG2 and reduces ROS production in MSCs. These effects should be taken into account when considering therapeutic applications of stem cells.

Cited by 37 publications

References 28 publications

Laminarin protects against hydrogen peroxide-induced oxidative damage in MRC-5 cells possibly via regulating NRF2

Laminarin protects against hydrogen peroxide-induced oxidative damage in MRC-5 cells possibly via regulating NRF2

Oxidized Extracellular DNA as a Stress Signal in Human Cells

Effects of Stress on the Results of Economic Activity of Business Entities

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