scbmtБИОМЕДИЦИНАJournal Biomed2074-59822713-0428Scientific center of biomedical technologies of Federal Medical and Biological Agencyscbmt-721Research ArticleСтатьиРоль ядерных рецепторов в регуляции биотрансформации ксенобиотиковЛаринаС. Н.noemail@neicon.ruИгнатьевИ. В.noemail@neicon.ruЧебышевН. В.noemail@neicon.ruКукесВ. Г.elmed@yandex.ruМосковская медицинская академия им. И.М.СеченоваRussian FederationИнститут клинической фармакологии ФГУ НЦЭСМП, МоскваRussian Federation20101302202011516Copyright © Ларина С.Н., Игнатьев И.В., Чебышев Н.В., Кукес В.Г., 20202020Ларина С.Н., Игнатьев И.В., Чебышев Н.В., Кукес В.Г.Ларина С.Н., Игнатьев И.В., Чебышев Н.В., Кукес В.Г.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.scbmt.ru/jour/article/view/721

Изучение генетической регуляции ферментов участвующих в метаболизме и выведении лекарств и ксенобиотиков, представляет большой интерес для понимания молекулярных механизмов ответа на лекарства. Гидрофобные лиганды и ряд ядерных рецепторов участвуют в индукции различных ферментов и транспортеров I, II и III фазы метаболизма ксенобиотиков. Ядерные рецепторы являются лиганд-активируемыми транскрипционными факторами. Эти белки модулируют регуляцию целевых генов, взаимодействуя с их промоторными или энхансерными последовательностями в специфических участках. Целевыми генами являются ферменты метаболизма, такие как цитохромы Р450 (CYP), транспортеры и ядерные рецепторы. Лиганд активируемые ядерные рецепторы играют важную роль в процессе восприятия токсических веществ, включая лекарства, вещества, загрязняющие окружающую среду и компоненты питания. Ключевым регулятором экспрессии CYP3A, метаболизирующего более 50 процентов лекарств у млекопитающих, является PXR ядерный рецептор. Сравнение аминокислотных последовательностей лиганд-связывающих доменов PXR различных видов животных выявило необычно широкую дивергенцию у ортологичных рецепторов. Эти различия объясняют видовую специфичность в индукции Р450 под действием различных лекарств.

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