Redox-sensitive system of the antioxidant-responsive element as a new target for tuberculosis treatment

The emergence of drug-resistant TB caused by resistance to antibiotic strains of bacteria, prompted to search for new "organism-oriented" ("host-targeted") adjuvant treatment strategies. Free radical oxidation plays an important role in the development and exacerbation of the pat...

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Autores principales: P. M. Kozhin, N. K. Zenkov, A. V. Chechushkov, N. S. Zaytseva, N. V. Kandalintseva, E. B. Menshchikova
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Publicado: Scientific Сentre for Family Health and Human Reproduction Problems 2016
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spelling oai:doaj.org-article:ece0e2e1174a4d0ab8f692336b6806452021-11-23T06:14:34ZRedox-sensitive system of the antioxidant-responsive element as a new target for tuberculosis treatment2541-94202587-959610.12737/article_590823a49422a0.54537639https://doaj.org/article/ece0e2e1174a4d0ab8f692336b6806452016-05-01T00:00:00Zhttps://www.actabiomedica.ru/jour/article/view/195https://doaj.org/toc/2541-9420https://doaj.org/toc/2587-9596The emergence of drug-resistant TB caused by resistance to antibiotic strains of bacteria, prompted to search for new "organism-oriented" ("host-targeted") adjuvant treatment strategies. Free radical oxidation plays an important role in the development and exacerbation of the pathological process. The main system of cell protection from oxidative stress is the redox-sensitive signaling system of the antioxidant-responsive element of the Keap1/Nrf2/ARE, which includes the transcription factor Nrf2, which is under constant control of a repressor protein Keapl. Nrf2 regulates the expression of genes containing the antioxidant-responsive element ARE in their promoters, Keapl is a kind of molecular "sensor" of modifications in the intracellular homeostasis. The inextricable link between these molecular structures allows combining them into a single redox-sensitive signaling system Keap1/Nrf2/ARE. Nrf2 modulates resistance of the organism to various infections: activation of Nrf2 prevents the penetration and replication of influenza A virus, contributes to resistance to various bacterial agents (Salmonella typhimurium, Pseudomonas aeruginosa). The aim of this work was to study the influence of induction system Keap1/Nrf2/ARE on the formation of mycobacterial granulomas in vitro. In vitro model was used to study effect of induction of the redox-sensitive signaling system Keap1/Nrf2/ARE in time course of granuloma formation. It was found that the activation of Keap1/Nrf2/ARE system led to acceleration of granuloma formation, which was then replaced by the dissociation process. These data allowed us to consider Keapl/Nrß/ARE system as a new therapeutic target in the tuberculosis treatment.P. M. KozhinN. K. ZenkovA. V. ChechushkovN. S. ZaytsevaN. V. KandalintsevaE. B. MenshchikovaScientific Сentre for Family Health and Human Reproduction Problemsarticlegranulomatous inflammationtuberculosismacrophageskeap1/nrf2/are systemts-13ScienceQRUActa Biomedica Scientifica, Vol 1, Iss 3(2), Pp 92-95 (2016)
institution DOAJ
collection DOAJ
language RU
topic granulomatous inflammation
tuberculosis
macrophages
keap1/nrf2/are system
ts-13
Science
Q
spellingShingle granulomatous inflammation
tuberculosis
macrophages
keap1/nrf2/are system
ts-13
Science
Q
P. M. Kozhin
N. K. Zenkov
A. V. Chechushkov
N. S. Zaytseva
N. V. Kandalintseva
E. B. Menshchikova
Redox-sensitive system of the antioxidant-responsive element as a new target for tuberculosis treatment
description The emergence of drug-resistant TB caused by resistance to antibiotic strains of bacteria, prompted to search for new "organism-oriented" ("host-targeted") adjuvant treatment strategies. Free radical oxidation plays an important role in the development and exacerbation of the pathological process. The main system of cell protection from oxidative stress is the redox-sensitive signaling system of the antioxidant-responsive element of the Keap1/Nrf2/ARE, which includes the transcription factor Nrf2, which is under constant control of a repressor protein Keapl. Nrf2 regulates the expression of genes containing the antioxidant-responsive element ARE in their promoters, Keapl is a kind of molecular "sensor" of modifications in the intracellular homeostasis. The inextricable link between these molecular structures allows combining them into a single redox-sensitive signaling system Keap1/Nrf2/ARE. Nrf2 modulates resistance of the organism to various infections: activation of Nrf2 prevents the penetration and replication of influenza A virus, contributes to resistance to various bacterial agents (Salmonella typhimurium, Pseudomonas aeruginosa). The aim of this work was to study the influence of induction system Keap1/Nrf2/ARE on the formation of mycobacterial granulomas in vitro. In vitro model was used to study effect of induction of the redox-sensitive signaling system Keap1/Nrf2/ARE in time course of granuloma formation. It was found that the activation of Keap1/Nrf2/ARE system led to acceleration of granuloma formation, which was then replaced by the dissociation process. These data allowed us to consider Keapl/Nrß/ARE system as a new therapeutic target in the tuberculosis treatment.
format article
author P. M. Kozhin
N. K. Zenkov
A. V. Chechushkov
N. S. Zaytseva
N. V. Kandalintseva
E. B. Menshchikova
author_facet P. M. Kozhin
N. K. Zenkov
A. V. Chechushkov
N. S. Zaytseva
N. V. Kandalintseva
E. B. Menshchikova
author_sort P. M. Kozhin
title Redox-sensitive system of the antioxidant-responsive element as a new target for tuberculosis treatment
title_short Redox-sensitive system of the antioxidant-responsive element as a new target for tuberculosis treatment
title_full Redox-sensitive system of the antioxidant-responsive element as a new target for tuberculosis treatment
title_fullStr Redox-sensitive system of the antioxidant-responsive element as a new target for tuberculosis treatment
title_full_unstemmed Redox-sensitive system of the antioxidant-responsive element as a new target for tuberculosis treatment
title_sort redox-sensitive system of the antioxidant-responsive element as a new target for tuberculosis treatment
publisher Scientific Сentre for Family Health and Human Reproduction Problems
publishDate 2016
url https://doaj.org/article/ece0e2e1174a4d0ab8f692336b680645
work_keys_str_mv AT pmkozhin redoxsensitivesystemoftheantioxidantresponsiveelementasanewtargetfortuberculosistreatment
AT nkzenkov redoxsensitivesystemoftheantioxidantresponsiveelementasanewtargetfortuberculosistreatment
AT avchechushkov redoxsensitivesystemoftheantioxidantresponsiveelementasanewtargetfortuberculosistreatment
AT nszaytseva redoxsensitivesystemoftheantioxidantresponsiveelementasanewtargetfortuberculosistreatment
AT nvkandalintseva redoxsensitivesystemoftheantioxidantresponsiveelementasanewtargetfortuberculosistreatment
AT ebmenshchikova redoxsensitivesystemoftheantioxidantresponsiveelementasanewtargetfortuberculosistreatment
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