Russian Journal of Biological Physics and Chemisrty Russian Journal of Biological Physics and Chemisrty АКТУАЛЬНЫЕ ВОПРОСЫ БИОЛОГИЧЕСКОЙ ФИЗИКИ И ХИМИИ 2499-9962 83068 10.29039/rusjbpc.2023.0588 МЕДИЦИНСКАЯ БИОФИЗИКА И БИОФИЗИЧЕСКАЯ ХИМИЯ MEDICAL BIOPHYSICS AND BIOPHYSICAL CHEMISTRY МЕДИЦИНСКАЯ БИОФИЗИКА И БИОФИЗИЧЕСКАЯ ХИМИЯ SIGMA-1 RECEPTOR ANTAGONIST, COMPOUND BD-1063, ATTENUATES Ca2+ RESPONSES INDUCED BY MOLIXAN IN MACROPHAGES АНТАГОНИСТ РЕЦЕПТОРОВ СИГМА-1, СОЕДИНЕНИЕ BD-1063, ПОДАВЛЯЕТ Са2+-ОТВЕТЫ, ВЫЗЫВАЕМЫЕ МОЛИКСАНОМ В МАКРОФАГАХ Миленина Л. С. Milenina L. S. l.milenina@spbu.ru Крутецкая З. И. Krutetskaya Z. I. z.krutetskya@spbu.ru Антонов В. Г. Antonov V. G. Крутецкая Н. И. Krutetskaya N. I. Бадюлина В. И. Badulina V. I. Симонян А. О. Simonyan A. O. Санкт-Петербургский государственный университет Санкт-Петербург Россия Saint-Petersburg State University Saint Petersburg Russian Federation Санкт-Петербургский государственный университет Санкт-Петербург Россия Saint-Petersburg State University Saint Petersburg Russian Federation Санкт-Петербургский государственный педиатрический медицинский университет Санкт-Петербург Россия Saint-Petersburg State Pediatric Medical University Saint Petersburg Russian Federation Военно-Медицинская академия им. C.М. Кирова Санкт-Петербург Россия Kirov Military Medical Academy Saint Petersburg Russian Federation Санкт-Петербургский государственный университет Санкт-Петербург Россия Saint-Petersburg State University Saint Petersburg Russian Federation Санкт-Петербургский государственный университет Санкт-Петербург Россия Saint-Petersburg State University Saint Petersburg Russian Federation Санкт-Петербургский государственный университет Санкт-Петербург Россия Saint-Petersburg State University Saint Petersburg Russian Federation 16 05 2024 16 05 2024 8 1 52 58 30 06 2023 https://rusjbpc.ru/en/nauka/article/83068/view

Рецепторы сигма-1 – повсеместные многофункциональные лигандрегулируемые молекулярные шапероны в мембране эндоплазматического ретикулума, имеющие уникальную историю, структуру и фармакологический профиль. Выполняя функции шаперонов, рецепторы сигма-1 модулируют широкий спектр клеточных процессов в норме и патологии, включая процессы Ca2+-сигнализации. Фармакологический аналог окисленного глутатиона препарат моликсан® используется как иммуномодулятор и цитопротектор в комплексной терапии бактериальных, вирусных и онкологических заболеваний; эффективен в профилактике и лечении коронавирусной инфекции COVID-19. Для выявления участия рецепторов сигма-1 во влиянии моликсана на внутриклеточную концентрацию Са2+ в макрофагах и в регуляции процессов Са2+-сигнализации в макрофагах в целом, исследовали влияние избирательного антагониста рецепторов сигма-1, соединения BD-1063, на Са2+-ответы, вызываемые моликсаном в перитонеальных макрофагах крысы. С использованием флуоресцентного Са2+-зонда Fura-2АМ впервые показано, что соединение BD-1063 значительно подавляет мобилизацию Са2+ из внутриклеточных Са2+-депо и последующий депозависимый вход Са2+ в клетки, индуцируемые моликсаном в перитонеальных макрофагах. Полученные данные свидетельствуют об участии рецепторов сигма-1 в комплексном сигнальном каскаде, вызываемом моликсаном и приводящем к увеличению внутриклеточной концентрации Са2+ в макрофагах, а также об участии рецепторов сигма-1 в регуляции депозависимого входа Са2+ в макрофагах.

Sigma-1 receptors are ubiquitous multifunctional ligand-operated molecular chaperones in the endoplasmic reticulum membrane with a unique history, structure, and pharmacological profile. Acting as chaperones, sigma-1 receptors modulate a wide range of cellular processes in health and disease, including Ca2+ signaling processes. The pharmacological analogue of oxidized glutathione, drug molixan®, is used as an immunomodulator and cytoprotector in the complex therapy of bacterial, viral and oncological diseases; effective in the prevention and treatment of coronavirus infection COVID-19. To elucidate the involvement of sigma-1 receptors in the effect of molixan on the intracellular Ca2+ concentration in macrophages and in the regulation of Ca2+ signaling processes in macrophages in general, the effect of the sigma-1 receptor selective antagonist, compound BD-1063, on Ca2+ responses induced by molixan in rat peritoneal macrophages was investigated. Using Fura-2AM microfluorimetry we have shown for the first time that compound BD-1063 significantly suppresses both Ca2+ mobilization from intracellular Ca2+ stores and subsequent store-dependent Ca2+ entry, induced by molixan in peritoneal macrophages. The data obtained indicate the involvement of sigma-1 receptors in the complex signaling cascade triggered by molixan and leading to intracellular Ca2+ concentration increase in macrophages. The results also suggest the involvement of sigma-1 receptors in the regulation of store-dependent Ca2+ entry in macrophages.

 соединение BD-1063 рецепторы сигма-1 внутриклеточная концентрация Са2+ макрофаги compound BD-1063 sigma-1 receptors intracellular Ca2+ concentration macrophages Работа выполнена в рамках Договора СПбГУ на выполнение научно-исследовательских работ № 05/03-20 от 12.03.2020.

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