Glutathione-related substances maintain cardiomyocyte contractile function in hypoxic conditions

Poluektov, Y.M.; Petrushanko, I.Y.; Undrovinas, N.A.; Lakunina, V.A.; Khapchaev, A.Y.; Kapelko, V.I.; Abramov, A.A.; Lakomkin, V.L.; Novikov, M.S.; Shirinsky, V.P.; Mitkevich, V.A.; Makarov, A.A.

Статья опубликована в высокорейтинговом журнале

Информация о цитировании статьи получена из Web of Science, Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 15 апреля 2020 г.

Авторы: Poluektov Y.M., Petrushanko I.Yu, Undrovinas N.A., Lakunina V.A., Khapchaev A.Y., Kapelko V.I., Abramov A.A., Lakomkin V.L., Novikov M.S., Shirinsky V.P., Mitkevich V.A., Makarov A.A.
Журнал: Scientific reports
Том: 9
Год издания: 2019
Издательство: Nature Publishing Group
Местоположение издательства: United Kingdom
Первая страница: e4872
DOI: 10.1038/s41598-019-41266-2
Аннотация: Severe hypoxia leads to decline in cardiac contractility and induces arrhythmic events in part due to oxidative damage to cardiomyocyte proteins including ion transporters. this results in compromised handling of Ca2+ ions that trigger heart contractile machinery. Here, we demonstrate that thiolcontaining compounds such as N-acetylcysteine (NAC), glutathione ethyl ester (et-GSH), oxidized tetraethylglutathione (tet-GSSG), oxidized glutathione (GSSG) and S-nitrosoglutathione (GSNO) are capable of reducing negative effects of hypoxia on isolated rat cardiomyocytes. Preincubation of cardiomyocytes with 0.1 mM GSNO, 0.5 mM et-GSH, GSSG, tet-GSSG or with 10 mM NAC allows cells 5-times longer tolerate the hypoxic conditions and elicit regular Ca2+ transients in response to electric pacing. the shape of Ca2+ transients generated in the presence of GSNO, et-GSH and NAC was similar to that observed in normoxic control cardiomyocytes. The leader compound, GSNO, accelerated by 34% the recovery of normal contractile function of isolated rat heart subjected to ischemia-reperfusion. GSNO increased glutathionylation of Na,K-ATPase alpha-2 subunit, the principal ion-transporter of cardiac myocyte sarcolemma, which prevents irreversible oxidation of Na,K-ATPase and regulates its function to support normal Ca2+ ion handling in hypoxic cardiomyocytes. Altogether, GSNO appears effective cardioprotector in hypoxic conditions worth further studies toward its cardiovascular application.
Добавил в систему: Хапчаев Аскер Юсуфович

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Glutathione-related substances maintain cardiomyocyte contractile function in hypoxic conditionsстатья Электронная публикация

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