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Search for intermediates of Na+,K+-ATPase-mediated [Na+]i/[K+]i-independent death signaling triggered by cardiotonic steroidsстатья
Информация о цитировании статьи получена из
Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 28 мая 2015 г.
- Авторы: Akimova O.A., Lopina O.D., Hamet P., Orlov S.N.
- Журнал: Pathophysiology
- Том: 12
- Номер: 2
- Год издания: 2005
- Издательство: MDPI Publishing
- Местоположение издательства: Basel, Switzerland, Switzerland
- Первая страница: 125
- Последняя страница: 135
- Аннотация: Previously, we reported that ouabain and other cardiotonic steroids (CTS) kill renal epithelial and vascular endothelial cells via their interaction with the Na+,K+-ATPase alpha-subunit, but independently of elevation of the [Na+]i/[K+]i ratio. In distinct cell types, side-by-side with inhibition of Na+,K+-ATPase-mediated ion fluxes, CTS trigger [Ca2+]i oscillation, activation of Ras, mitogen-activated protein kinases (MAPK), phosphoinositide-3 kinase (PI3K), and protein kinase C as well as the production of reactive oxygen species and cytoskeleton reorganization. This study examined the potential involvement of the above-listed intermediates in death signaling triggered by ouabain in C7-Madin-Darby canine kidney cells. In these cells, twofold decreased staining with dimethylthiazol diphenyltetrazolium (MTT) and detachment of up to 80% of dead cells were detected in 6 and 24 h of ouabain addition, respectively. We did not observe any effect of extra- (EGTA) and intracellular (BAPTA) Ca2+-chelators, [Ca2+]i-raising compounds (thapsigargin, ATP), inhibitors of Ras signaling (alpha-hydroxyfarnesyl-sulphosphoric acid), PI3K (wortmannin), MAPK ERK1/2 kinase (PD98059), tyrosine kinases (genistein) as well as activators (4beta-PMA, 8-Br-cAMP, 8-Br-cGMP, forskolin) and inhibitors (calphostin) of serine-threonine kinases on MTT staining and death of ouabain-treated cells. Ouabain did not affect cellular redox state and the production of superoxide anion and hydroperoxide. Neither N-acetylcysteine nor reduced gluthatione suppressed the death of ouabain-treated cells. Thus, our results show that none of the above-listed signaling systems plays a major role in the development of Nai+,Ki+-independent death machinery triggered by CTS interaction with the Na+,K+-ATPase alpha-subunit.
- Добавил в систему: Лопина Ольга Дмитриевна