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Взаимосвязи компонентов JAK/STAT- и MAPK/SAPK-сигнальных путей, а также NF-kB и содержания в мононуклеарных клетках цельной крови тиоредоксинредуктазы в постклиническую стадию внебольничной пневмонии
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Bondar S.S., Terekhov I.V., Nikiforov V.S. et al. The relationship of JAK/STAT and MAPK/SAPK signaling pathways, NF-kB and content in the mononuclear cells of whole blood thioredoxins in the post-clinical stage of community-acquired pneumonia. Consilium Medicum. 2018; 20 (11): 61–65. DOI: 10.26442/20751753.2018.11.180091
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Ключевые слова: тиоредоксинредуктаза, STAT5A, p38, пневмония, антиоксиданты.
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The study discusses the relationship between the content of mononuclear cells in peripheral blood (MNC) of the MAPK/SAPK and JAK/STAT-signaling pathways, nuclear transcription factor NF-kB, and thioredoxin reductase. The content and level of phosphorylation of signal transducers and transcription activators STAT3, STAT5A, STAT6, nuclear transcription factor NF-kB (IkBa), stress-activated protein kinases JNK, ERK, mitogen-activated protein kinase p38, the level of nuclear transcription factor NF-kB subunit p65 were determined by enzyme immunoassay in MNCs. The results of the study indicate that the stage of reconvalescence of VP is characterized by a deficiency of antioxidant protection, manifested by a decrease in the concentration of antioxidants by 6.7% (p=0.051), despite the existing increase in the level of MNC thioredoxin reductase by 16.3% (p=0.028). This fact indicates the need for correction of the state of AOSIS in patients who have undergone EAP. The analysis revealed a significant relationship between the level of TR and STAT5A, as well as the content of P65 and STAT6, characterized by a positive correlation with these factors.
Key words: thioredoxins, STAT5A, p38, pneumonia, antioxidants.
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4. Dagnell M, Pace PE, Cheng Q et al. Thioredoxin reductase 1 and NADPH directly protect protein tyrosine phosphatase 1B from inactivation during H2O2 exposure. J Biol Chem 2017; 292 (35): 14371–80. DOI: 10.1074/jbc.M117.793745
5. Bassi R, Burgoyne JR, DeNicola GF et al. Redox-dependent dimerization of p38a mitogen-activated protein kinase with mitogen-activated protein kinase kinase 3. J Biol Chem 2017; 292 (39): 16161–73. DOI: 10.1074/jbc.M117.785410
6. Kesarwani P, Murali AK, Al-Khami AA, Mehrotra S. Redox Regulation of T-Cell Function: From Molecular Mechanisms to Significance in Human Health and Disease. Antioxidants Redox Signal 2013; 18 (12): 1497–534. DOI: 10.1089/ars.2011.4073
7. Kim S-H, Oh J, Choi J-Y et al. Identification of human thioredoxin as a novel IFN-gamma-induced factor: Mechanism of induction and its role in cytokine production. BMC Immunol 2008; 9: 64. DOI: 10.1186/1471-2172-9-64
8. Matthews JR, Wakasugi N, Virelizier JL et al. Thioredoxin regulates the DNA binding activity of NF-kappa B by reduction of a disulphide bond involving cysteine 62. Nucleic Acids Res 1992; 20 (15): 3821–30.
9. Gromov M.S., Terekhov I.V. Kharakteristika sistemnogo vospalitel'nogo otveta u bol'nykh vnebol'nichnoi pnevmoniei v dinamike pri pomoshchi aktivnoi SVCh-radiometrii. Kazanskii med. zhurn. 2010; 91 (5): 611–4. [in Russian]
10. Terekhov I.V., Bondar' S.S., Khadartsev A.A. Laboratornoe opredelenie vnutrikletochnykh faktorov protivovirusnoi zashchity pri vnebol'nichnoi pnevmonii v otsenke effektov nizkointensivnogo SVCh-izlucheniia. Klin. laboratornaia diagnostika. 2016; 61 (6): 380–4. [in Russian]
11. Lee S, Kim SM, Lee RT. Thioredoxin and Thioredoxin Target Proteins: From Molecular Mechanisms to Functional Significance. Antioxidants Redox Signal 2013; 18 (10): 1165–207. DOI: 10.1089/ars.2011.4322
12. Solodukhin K.A., Nikiforov V.S., Gromov M.S. i dr. Vliianie nizkointensivnogo SVCh-oblucheniia na vnutrikletochnye protsessy v mononuklearakh pri pnevmonii. Med. immunologiia. 2012; 14 (6): 541–4. [in Russian]
13. Linher-Melville K, Singh G. The complex roles of STAT3 and STAT5 in maintaining redox balance: Lessons from STAT-mediated xCT expression in cancer cells. Mol Cel Endocrinol 2017; 451: 40–52. DOI: 10.1016/j.mce.2017.02.014
14. Dwivedi G, Gran MA, Bagchi P, Kemp ML. Dynamic Redox Regulation of IL-4 Signaling. Saucerman JJ, ed. PLoS Computational Biol 2015; 11 (11): e1004582. DOI: 10.1371/journal.pcbi.1004582
15. Muri J, Heer S, Matsushita M et al. The thioredoxin-1 system is essential for fueling DNA synthesis during T-cell metabolic reprogramming and proliferation. Nat Commun 2018; 9 (1): 1851. DOI: 10.1038/s41467-018-04274-w
1 ФГБОУ ВО «Тульский государственный университет». 300012, Россия, Тула, пр. Ленина, д. 92;
4 ФГБОУ ВО «Орловский государственный университет им. И.С.Тургенева». 302026, Россия, Орел, ул. Комсомольская, д. 95
*trft@mail.ru
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S.S.Bondar1, I.V.Terekhov*1, V.S.Nikiforov2, V.K.Parfenyuk3, N.V.Bondar4
1Tula State University. 300012, Russian Federation, Tula, pr. Lenina, d. 92;
2 I.I.Mechnikov North-West State Medical University of the Ministry of Health of the Russian Federation. 191015, Russian Federation, Saint Petersburg, ul. Kirochnaia, d. 41;
3 V.I.Razumovsky Saratov State Medical University of the Ministry of Health of the Russian Federation. 410012, Russian Federation, Saratov, ul. Bol'shaia Kazach'ia, d. 112;
4 I.S.Turgenev Orel State University. 302026, Russian Federation, Orel, ul. Komsomolskaya, d. 95
*trft@mail.ru