Влияние внутриклеточной регуляции метаболизма на популяционный состав лимфоцитов периферической крови человека
DOI:
https://doi.org/10.37482/2687-1491-Z155Ключевые слова:
индуцируемый гипоксией фактор 1-альфа, сиртуин 3, аденозинтрифосфат (АТФ), клеточный иммунитет, популяции лимфоцитов, иммунометаболизмАннотация
Метаболическая активность оказывает существенное влияние на дифференцировку, пролиферацию и функционирование Т-клеток. Различные субпопуляции лимфоцитов в разной степени используют гликолиз и митохондриальный метаболизм, основными регуляторами которых являются индуцируемый гипоксией фактор 1-альфа (HIF-1α) и сиртуин 3 (SIRT3) соответственно. Цель исследования – выявить характер изменений популяционного состава лимфоцитов периферической крови человека в зависимости от уровней внутриклеточных регуляторов метаболизма SIRT3 и HIF-1α. Материалы и методы. Обследовано 227 жителей г. Архангельска и Архангельской области, средний возраст которых составил 42±11 лет. Абсолютное содержание лимфоцитов в венозной крови определялось на гематологическом анализаторе Sysmex XS 500i, содержание фенотипов CD3+, CD4+, CD8+, CD10+, CD25+ , CD95+ – методом непрямой иммунопероксидазной реакции. Внутриклеточное содержание аденозинтрифосфата (АТФ) было измерено биолюминесцентным методом с использованием люциферазы. Концентрации HIF-1α и SIRT3 измерялись в лизате лимфоцитов при помощи иммуноферментного анализа. Для разделения общей выборки на группы по содержанию SIRT3 и HIF-1α применялся кластерный анализ (метод k-средних). Результаты. Внутриклеточная концентрация SIRT3 и HIF-1α изменялась согласованно с внутриклеточной концентрацией АТФ. Установлено, что в группе с высокой концентрацией HIF-1α удельный вес CD4+, CD8+, CD10+, CD25+-лимфоцитов был выше, чем в группе с высокой концентрацией SIRT3, в которой выше был удельный вес CD95+-лимфоцитов. Таким образом, содержание внутриклеточных регуляторов метаболизма, координирующих работу путей наработки АТФ в клетке – окислительное фосфорилирование (SIRT3) и гликолиз (HIF-1α), влияет на популяционный состав лимфоцитов и поэтому важно для оценки иммунного реагирования.
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Библиографические ссылки
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Shyer J.A., Flavell R.A., Bailis W. Metabolic Signaling in T Cells. Cell Res., 2020, vol. 30, no. 8, pp. 649–659. DOI: 10.1038/s41422-020-0379-5
Kierans S.J., Taylor C.T. Regulation of Glycolysis by the Hypoxia-Inducible Factor (HIF): Implications for Cellular Physiology. J. Physiol., 2021, vol. 599, no. 1, pp. 23–37. DOI: 10.1113/JP280572
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Fu X., Li K., Niu Y., Lin Q., Liang H., Luo X., Liu L., Li N. The mTOR/PGC-1α/SIRT3 Pathway Drives Reductive Glutamine Metabolism to Reduce Oxidative Stress Caused by ISKNV in CPB Cells. Microbiol. Spectr., 2022, vol. 10, no. 1. Art. no. e0231021. DOI: 10.1128/spectrum.02310-21
Steinert E.M., Vasan K., Chandel N.S. Mitochondrial Metabolism Regulation of T Cell-Mediated Immunity. Annu. Rev. Immunol., 2021, vol. 39, pp. 395–416. DOI: 10.1146/annurev-immunol-101819-082015
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Dang E.V., Barbi J., Yang H.-Y., Jinasena D., Yu H., Zheng Y., Bordman Z., Fu J., Kim Y., Yen H.-R., Luo W., Zeller K., Shimoda L., Topalian S.L., Semenza G.L., Dang C.V., Pardoll D.M., Pan F. Control of TH17/Treg Balance by Hypoxia-Inducible Factor 1. Cell, 2011, vol. 146, no. 5, pp. 772–784. DOI: 10.1016/j.cell.2011.07.033
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Biswas S., Troy H., Leek R., Chung Y.-L., Li J.-L., Raval R.R., Turley H., Gatter K., Pezzella F., Griffiths J.R., Stubbs M., Harris A.L. Effects of HIF-1α and HIF2α on Growth and Metabolism of Clear-Cell Renal Cell Carcinoma 786-0 Xenografts. J. Oncol., 2010, vol. 2010. Art. no. 757908. DOI: 10.1155/2010/757908
Yu W., Denu R.A., Krautkramer K.A., Grindle K.M., Yang D.T., Asimakopoulos F., Hematti P., Denu J.M. Loss of SIRT3 Provides Growth Advantage for B Cell Malignancies. J. Biol. Chem., 2016, vol. 291, no. 7, pp. 3268–3279. DOI: 10.1074/jbc.M115.702076
Zamaraeva M.V., Sabirov R.Z., Maeno E., Ando-Akatsuka Y., Bessonova S.V., Okada Y. Cells Die with Increased Cytosolic ATP During Apoptosis: A Bioluminescence Study with Intracellular Luciferase. Cell Death Differ., 2005, vol. 12, no. 11, pp. 1390–1397. DOI: 10.1038/sj.cdd.4401661
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Neeli P.K., Gollavilli P.N., Mallappa S., Hari S.G., Kotamraju S. A Novel Metadherinδ7 Splice Variant Enhances Triple Negative Breast Cancer Aggressiveness by Modulating Mitochondrial Function via NFĸB-SIRT3 Axis. Oncogene, 2020, vol. 39, no. 10, pp. 2088–2102. DOI: 10.1038/s41388-019-1126-6
