medgenМедицинская генетикаMedical Genetics2073-7998Publishing House «Genius Media» LLC10.25557/2073-7998.2024.01.3-18medgen-2406Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL RESEARCHАдаптивные реакции фибробластов легких эмбриона человека на производное фуллерена, модифицированного остатками 3-бензотиенилаланинаAdaptive reactions of human embryo lung fibroblasts (HELF) to a fullerene derivative modified with 3-benzothienylalanine residuesКостюкС. В.KostyukS. V.

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ул. Москворечье, д. 1

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МалиновскаяЕ. М.MalinovskayaE. M.

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ЕршоваЕ. С.ErshovaE. S.

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КаменеваЛ. В.KamenevaL. V.

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СавиноваЕ. А.SavinovaE. A.

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КостюкС. Э.KostyukS. E.

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Москва

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Moscow

СалимоваТ. А.SalimovaT. A.

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ЖиленковА. В.ZhilenkovA. V.

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пр. акад. Семенова, д. 1

Черноголовка

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1, Semenov Prospect

Chernogolovka

КраеваяО. А.KraevayaO. A.

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пр. акад. Семенова, д. 1

Черноголовка

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Chernogolovka

ТрошинП. А.TroshinP. A.

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пр. акад. Семенова, д. 1

Черноголовка

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Chernogolovka

ИжевскаяВ. Л.IzhevskayaV. L.

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КуцевС. И.KutsevS. I.

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ВейкоН. Н.VeikoN. N.

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ФГБНУ «Медико-генетический научный центр имени академика Н.П. Бочкова»РоссияResearch Centre for Medical GeneticsRussian FederationФедеральный исследовательский центр проблем химической физики и медицинской химии Российской академии наукРоссияFederal Research Center for Problems of Chemical Physics and Medicinal Chemistry of RASRussian Federation202405032024231318Copyright © Костюк С.В., Малиновская Е.М., Ершова Е.С., Каменева Л.В., Савинова Е.А., Костюк С.Э., Салимова Т.А., Жиленков А.В., Краевая О.А., Трошин П.А., Ижевская В.Л., Куцев С.И., Вейко Н.Н., 20242024Костюк С.В., Малиновская Е.М., Ершова Е.С., Каменева Л.В., Савинова Е.А., Костюк С.Э., Салимова Т.А., Жиленков А.В., Краевая О.А., Трошин П.А., Ижевская В.Л., Куцев С.И., Вейко Н.Н.Kostyuk S.V., Malinovskaya E.M., Ershova E.S., Kameneva L.V., Savinova E.A., Kostyuk S.E., Salimova T.A., Zhilenkov A.V., Kraevaya O.A., Troshin P.A., Izhevskaya V.L., Kutsev S.I., Veiko N.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.medgen-journal.ru/jour/article/view/2406

   Исследовано влияние производного фуллерена с пятью присоединенными остатками 3-бензотиенилаланина и одним атомом водорода (Ф1) на функционирование фибробластов легких эмбриона человека (ФЛЭЧ). Показали, что Ф1 в течение 24 часов проникает в цитоплазму большинства клеток в популяции. Для исследования воздействия Ф1 на ФЛЭЧ выбраны две концентрации: 18,3 нг/мл, входящая в диапазон нетоксичных концентраций, и концентрация, близкая к повреждающей – 28 µг/мл, и три времени инкубации клеток с соединениями – 1, 3 и 24 часа. Обнаружили, что через 24 часа в присутствии низких концентраций Ф1 снижается уровень активных форм кислорода (АФК) в клетках, что обусловлено повышением экспрессии гена NRF2 и увеличением его функциональной активности. Соединение Ф1 в концентрации, близкой к токсичной, вызывает в культивируемых ФЛЭЧ повышение уровня экспрессии гена и белка NOX4, что приводит к синтезу АФК в клетках, к окислительным модификациям и двунитевым разрывам ДНК ядер клеток через 24 часа инкубации. Не обнаружено влияния Ф1 на уровень экспрессии гена и белка BRCA1 что, вероятно, способствует образованию в клетках и поддержанию на высоком уровне двунитевых разрывов ДНК через 24 часа инкубации. Повышение экспрессии антиапоптотических генов в ФЛЭЧ через 24 часа культивирования с Ф1 может способствовать выживанию клеток с поврежденной ДНК.

   We investigated the effort of fullerene derivative with five attached residues of 3-benzothienylalanine and one hydrogen atom (F1) on the functioning of the human embryonic lung fibroblasts (HELF). It was shown that F1 penetrates the cytoplasm of most cells in the population within 24 hours. To study the effect of F1 on HELF, two concentrations were selected: 18.3 ng/ml, which is in the range of non–toxic concentrations and a concentration close to damaging – 28 µg/ml and three incubation times of cells with compounds – 1, 3 and 24 hours. It was found that after 24 hours in the presence of low concentrations of F1, the level of ROS in cells decreases, which is due to an increase in the expression of the NRF2 gene and an increase in its functional activity. The F1 compound in a concentration close to toxic causes an increase in the expression level of the NOX4 gene and protein in cultured HELF, which leads to the synthesis of ROS in cells and oxidative modifications, and double-stranded DNA breaks of cell nuclei after 24 hours of incubations. There was no effect of F1 on the expression level of the BRCA1 gene and protein, which probably contributes to the formation of double-stranded DNA breaks in cells and maintenance at a high level after 24 hours of incubation. An increase in the expression of anti-apoptotic genes in HELF after 24 hours of cultivation with F1 may contribute to the survival of cells with damaged DNA.

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The authors declare that there are no conflicts of interest present.