Единственный нормальный ген рецепторов ЛНП

Н. Миант с сотрудниками из Хаммерсмитской больницы в Лондоне показали, что то же самое происходит у людей при гомозиготной форме семейной гиперхолестеролемии.

Выяснение роли рецепторов ЛНП в развитии семейной гиперхолестеролемии позволило наметить пути лечения этого заболевания у части больных с гетерозиготной его формой. Если бы можно было заставить единственный нормальный ген рецепторов ЛНП у гетерозиготных больных синтезировать вдвое больше продукта, то у них восстановилось бы нормальное количество рецепторов ЛНП. На возможность такой компенсации указывали результаты исследований культивируемых фибробластов кожи, в которых была обнаружена регуляция синтеза рецепторов ЛНП на уровне транскрипции. Осуществляется она по принципу обратной связи: избыток холе- стерола тормозит синтез на генах рецепторов ЛНП матричной РНК, которая транслируется белоксинтезирующим аппаратом клетки с образованием белка-рецептора. Недостаток холсстерола стимулирует транскрипцию, что приводит к усилению синтеза рецепторов ЛНП. Мы обнаружили, что культивируемые клетки от гетерозиготных больных семейной гиперхолестеролемией продуцируют нормальное количество рецепторов ЛНП (путем усиления синтеза матричных РНК на единственном нормальном гене рецепторов ЛНП), если просто снизить концентрацию холестерола в культуральной среде. Как же создать аналогичный дефицит холестерола в организме больного?

Печень захватывает и утилизует наибольшее по сравнению с другими органами количество холестерола. Это обусловлено как ее большими размерами, так и высокой концентрацией в ней рецепторов ЛНП.



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