Background: Breast tumors are number one cause of cancer morbidity and mortality among women around the world, and Russia is not an exception. Many proteins that control proliferation of immortalized cells are redox-regulated, which is essential for modulating cellular proliferative activity, especially during tumor growth. Studying the role of glutaredoxin and glutathione in cell cycle phase distribution will allow not only to identify the molecular targets regulating cell proliferation, but also to develop methods of diagnosis and targeted therapy of socially sensitive diseases, including breast cancer, in the future.Aims: To evaluate the role of glutathione and glutaredoxin in the molecular mechanisms regulating MCF-7 breast cancer cell proliferation under the effects of roscovitine, a cyclin-dependent protein kinase inhibitor.Materials and methods: The MCF-7 cell line (human breast adenocarcinoma) was used in the study. The cell culture was incubated in the presence and absence of roscovitine in the final concentration of 20 µmol for 18 h. The production of reactive oxygen species, the distribution of cells between cell cycle phases and the amount of Annexin V positive cells were determined using flow cytometry. The concentrations of total, reduced and oxidized glutathione, protein SH groups and protein-bound glutathione were measured by spectrophotometry. The levels of glutaredoxin, cyclin E and cyclin-dependent protein kinases were estimated by Western blotting with monoclonal antibodies.Results: The effects of roscovitine in the MCF-7 cells resulted in cell cycle arrest in G2/М phases with the decreased levels of cyclin E and cyclin-dependent protein kinase 2. It was accompanied by activation of programmed cell death. In tumor cells incubated in the presence of roscovitine, oxidative stress was triggered, which was accompanied by the elevated generation of reactive oxygen species, the decrease in the concentration of reduced glutathione, and the rise in the level of glutaredoxin. It contributed to the increase in protein glutathionylation against the backdrop of the decreased SH group concentration.Conclusions: Breast cancer cell proliferation under the effects of roscovitine is reduced following not only the decrease in the cyclin level and cyclin-dependent protein kinase activity, but also the shift in the intracellular oxidant/antioxidant ratio. Roscovitine-induced oxidative stress in the MCF-7 cells contributed to protein glutathionylation with the changes in the protein structure and functions. It results in impaired cell cycle progression, indicating a possibility to regulate cellular proliferation through modulating functional properties of redox-dependent proteins using the glutathione/glutaredoxin system.
Aim. To evaluate the ratio of the fractions of classical, intermediate, non-classical and transitional monocytes in correlation with the concentration of interleukins 4 and 6 in the blood of patients with ischemic cardiomyopathy. Methods. 18 patients with ischemic cardiomyopathy (17 men and 1 woman) aged 47-66 years with circulatory insufficiency of functional class II-III according to the classification of heart failure of the New York Heart Association, were examined. The control group included 14 healthy donors matched by gender and age to patients with ischemic cardiomyopathy without any diseases of cardiovascular system and other systems in an exacerbation stage. In blood of the patients with ischemic cardiomyopathy, the relative content of classical (CD14++CD16-), intermediate (CD14++CD16+), non-classical (CD14+CD16+) and transitional (CD14+CD16-) monocytes was assessed by flow cytometry and the concentration of interleukins 4 and 6 by enzyme-linked immunosorbent assay (ELISA). Results. It was shown that the number of non-classical monocytes in the blood of patients with ischemic cardiomyopathy was 2 times lower than normal (5.05 % [4.08; 6.58] and 10.07 % [9.34; 13.84], respectively, p < 0.01), as well as the concentration of interleukin-4 (0.02 pg/ml [0; 0.04] and 0.15 pg/ml [0.05; 0.65], respectively, p < 0.05). The number of classical monocytes in the blood of patients had a tendency to decrease, and the proportion of intermediate monocytes and the concentration of interleukin-6, on the contrary, were slightly higher than in healthy individuals, and were interdependent (r = 0.61; p < 0.05). The relative content of transitional monocytes in the blood was comparable with that of healthy donors. Conclusions. The subpopulation composition of blood monocytes in patients with ischemic cardiomyopathy is characterized by a deficiency of the fraction of non-classical monocytes with protective properties against endothelium, and interleukin-4 in the blood with a certain increase in the content of interleukin-6 and the number of intermediate cells with ability to cooperate with T-lymphocytes, which predisposes to diffuse atheromatosis of small coronary arteries and diffuse hypoxic myocardial damage in ischemic cardiomyopathy.
Патологическое течение противоинфекцион-ного иммунного ответа и клиническая манифе-стация инфекционного заболевания возникают при нарушениях иммунологической реактивности организма. В случае адекватного взаимодополня-ющего функционирования систем врожденного и адаптивного иммунитета, напротив, происхо-дит своевременное уничтожение любого инфек-ционного антигена (вне зависимости от пути его проникновения в макроорганизм) на уровне «первой линии защиты», как правило, в системе мукозального иммунитета, то есть иммунитета слизистых оболочек. При инфицировании чело-УДК 616.23/.24-002.2+616.248]-036. 65:615.357:616.2-008.87 DOI 10.20538/168265:615.357:616.2-008.87 DOI 10.20538/ -0363-2016 Для цитирования: Чурина Е.Г., Уразова О.И., Новицкий В.В., Есимова И.Е., Кононова Т.Е., Филинюк О.В., Колобов-никова Ю.В., Дмитриева А.И. Факторы дисрегуляции иммунного ответа (на различных ýтапах его реализации) при туберкулезе легких. Бюллетень сибирской медицины. 2016; 15 (5): 166-177 Факторы дисрегуляции иммунного ответа (на различных этапах его реализации) при туберкулезе легких Чурина Е.Г. Россия, 634050, г. Томск, пр. Ленина, 36 РЕЗЮМЕ В статье представлен обзор научных исследований, раскрывающих механизмы неэффективной реализа-ции антигенспецифического иммунного ответа при туберкулезе легких в зависимости от клинической формы (инфильтративный и диссеминированный туберкулез легких) и варианта течения (лекарствен-но-чувствительный и лекарственно-устойчивый туберкулез легких) заболевания. Установлено, что ме-ханизмы иммунного дисбаланса при туберкулезе легких связаны с нарушением костимуляции сигналов, необходимых для активации Т-лимфоцитов, и иммуносупрессорным действием регуляторных Т-клеток как при их взаимодействии с дендритными клетками на индуктивной стадии иммунного ответа, так и в процессе дифференцировки и пролиферации эффекторных клеток с формированием супрессорного режима иммунорегуляции.Ключевые слова: туберкулез легких, иммунный ответ, регуляторные Т-клетки, иммунорегуляция.* Чурина Елена Георгиевна, e-mail: Lena1236@yandex.ru века Mycobacterium tuberculosis (МВТ) развитие и прогрессирующее течение туберкулеза легких (ТЛ) практически всегда связано с наличием у пациента вторичной иммунологической недо-статочности [1][2][3]. С другой стороны, в основе любого иммунопатологического процесса лежит первичная активация иммунных реакций, однако в случае туберкулезного воспаления она носит кратковременный и неýффективный характер и не приводит к полноценной реализации много-стадийного иммунного ответа с образованием специфичных к антигену клеток памяти. Установ-лено, что механизм иммунного дисбаланса при туберкулезной инфекции связан, прежде всего, с поляризацией иммунного ответа в направле-нии Treg-и Th2-зависимых путей [4][5][6]. В свою очередь, избыточное количество регуляторных Толерогенные дендритные клетки: особенности цитокинового профиля и роль в нарушении инициации Т-клеточного иммунного ответа при туберкулезе легкихПрезентация антигена является ключевым ýта-пом иммунного ответа. Нарушение представления...
Background: Redox status imbalance against the backdrop of oxidative stress development underlies the pathogenesis of a whole range of diseases. Many intracellular proteins contain free thiol groups and undergo redox regulation which is one of the key processes in controlling cell proliferation. Thioredoxin and glutaredoxin are involved in maintaining intracellular redox homeostasis and act as candidates in regulating proliferation. This provides prospects for future development of methods for diagnosis and targeted therapy of socially sensitive diseases accompanied by oxidative stress. The aim of the study is to reveal the role of redox proteins in molecular mechanisms of regulating HBL-100 breast epithelial cell proliferation under the effect of roscovitine, a cell cycle inhibitor. Materials and methods: Two research groups were formed. They included HBL-100 human breast epithelial cells incubated in the presence and absence of 20 mcM roscovitine for 18 hours. The intracellular thioredoxin levels were determined using Western blot analysis with specific monoclonal antibodies. Distribution of the cells among cell cycle phases were evaluated by flow cytometry. The activity of glutathione reductase, glutathione peroxidase, and thioredoxin reductase were measured by spectrophotometry. Results: Under the effect of roscovitine in the HBL-100 cells, cell cycle arrest in the G2/М phases occurred and oxidative stress developed. In the meantime, the decrease in the thioredoxin and glutaredoxin concentrations was registered along with the change in the functional activity of glutathione-dependent enzymes. Conclusions: Application of roscovitine, a cell cycle inhibitor, allowed creating a model of oxidative stress in the breast epithelial cells against the backdrop of inhibited cell proliferation. We identified that thioredoxin and glutaredoxin contributed to impairment of cell cycle progression. It points at a possibility to regulate cell proliferation by modulating the functional features of cellular redox-dependent proteins in different pathologies accompanied by oxidative stress.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.