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Российский физиологический журнал им. И.М. Сеченова, 2023, T. 109, № 9, стр. 1185-1198

Механизмы антипролиферативного действия стрептококковой аргининдеиминазы в отношении клеток лимфобластной лейкемии линии Jurkat

Э. А. Старикова 1, 2, 3, *, Дж. Т. Маммедова 1, А. Ожиганова 1, Л. А. Бурова 1, И. В. Кудрявцев 1, 2

1 Институт экспериментальной медицины
Санкт-Петербург, Россия

2 Первый Санкт-Петербургский государственный медицинский университет им. акад. И.П. Павлова Министерства здравоохранения Российской Федерации
Санкт-Петербург, Россия

3 Институт медицинского образования Национального медицинского исследовательского це-нтра им. В.А. Алмазова Министерства здравоохранения Российской Федерации
Санкт-Петербург, Россия

* E-mail: Starickova@yandex.ru

Поступила в редакцию 23.05.2023
После доработки 12.07.2023
Принята к публикации 21.07.2023

Аннотация

Стратегия депривации аргинина рассматривается как перспективное направление терапии раковых заболеваний. Целью исследования было изучение влияния аргининдеиминазы пиогенного стрептококка на клетки лимфобластной лейкемии Jurkat. Для этого сравнивали эффекты супернатантов разрушенных стрептококков исходного штамма, экспрессирующего аргининдеиминазу, и его изогенного мутанта с инактивированным геном аргининдеиминазы – arcA. Пролиферацию клеток оценивали в МТТ-тесте. Остальные параметры исследовали с помощью проточной цитометрии. Распределение клеток по фазам клеточного цикла изучали с использованием ДНК-связывающего красителя DAPI и антител против циклина А2. Интенсивность аутофагии оценивали с помощью реагента LysoTracker™ Green DND-26. Для оценки жизнеспособности клетки докрашивали DAPI. Исследования показали, что стрептококковый фермент подавлял пролиферативную активность клеток Jurkat, повышал долю клеток в фазах покоя G0/G1, снижал долю клеток в фазах синтеза S/G2 и усиливал аутофагию без снижения жизнеспособности. Добавка аргинина нивелировала эффекты аргининдеиминазы. Полученные результаты открывают возможность использования аргинин-гидролизующей активности стрептококкового фермента для сочетанной терапии онкологических заболеваний.

Ключевые слова: стрептококковая аргининдеиминаза, аргинин, клетки линии Jurkat, пролиферация, клеточный цикл, аутофагия

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