Comparative Action of Cardiotonic Steroids on Intracellular Processes in Rat Cortical Neurons
- Авторлар: Lopachev A.1, Lopacheva O.1,2, Nikiforova K.3, Filimonov I.2, Fedorova T.1, Akkuratov E.4,5
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Мекемелер:
- Research Center of Neurology
- International Biotechnological Center
- Institute of General Pathology and Pathophysiology
- Science for Life Laboratory, Department of Applied Physics
- Institute of Translational Biomedicine
- Шығарылым: Том 83, № 2 (2018)
- Беттер: 140-151
- Бөлім: Article
- URL: https://journals.rcsi.science/0006-2979/article/view/151599
- DOI: https://doi.org/10.1134/S0006297918020062
- ID: 151599
Дәйексөз келтіру
Аннотация
Binding to Na+,K+-ATPase, cardiotonic steroids (CTS) activate intracellular signaling cascades that affect gene expression and regulation of proliferation and apoptosis in cells. Ouabain is the main CTS used for studying these processes. The effects of other CTS on nervous tissue are practically uncharacterized. Previously, we have shown that ouabain affects the activation of mitogen-activated protein kinases (MAP kinases) ERK1/2, p38, and JNK. In this study, we compared the effects of digoxin and bufalin, which belong to different subclasses of CTS, on primary culture of rat cortical cells. We found that CTS toxicity is not directly related to the degree of Na+,K+-ATPase inhibition, and that bufalin and digoxin, like ouabain, are capable of activating ERK1/2 and p38, but with different concentration and time profiles. Unlike bufalin and ouabain, digoxin did not decrease JNK activation after long-term incubation. We concluded that the toxic effect of CTS in concentrations that inhibit less than 80% of Na+,K+-ATPase activity is related to ERK1/2 activation as well as the complex profile of MAP kinase activation. A direct correlation between Na+,K+-ATPase inhibition and the degree of MAP kinase activation is only observed for ERK1/2. The different action of the three CTS on JNK and p38 activation may indicate that it is associated with intracellular signaling cascades triggered by protein–protein interactions between Na+,K+-ATPase and various partner proteins. Activation of MAP kinase pathways by these CTS occurs at concentrations that inhibit Na+,K+-ATPase containing the α1 subunit, suggesting that these signaling cascades are realized via α1. The results show that the signaling processes in neurons caused by CTS can differ not only because of different inhibitory constants for Na+,K+-ATPase.
Негізгі сөздер
Авторлар туралы
A. Lopachev
Research Center of Neurology
Email: akkuratov.evgeny@gmail.com
Ресей, Moscow, 125367
O. Lopacheva
Research Center of Neurology; International Biotechnological Center
Email: akkuratov.evgeny@gmail.com
Ресей, Moscow, 125367; Moscow, 119991
K. Nikiforova
Institute of General Pathology and Pathophysiology
Email: akkuratov.evgeny@gmail.com
Ресей, Moscow, 125315
I. Filimonov
International Biotechnological Center
Email: akkuratov.evgeny@gmail.com
Ресей, Moscow, 119991
T. Fedorova
Research Center of Neurology
Email: akkuratov.evgeny@gmail.com
Ресей, Moscow, 125367
E. Akkuratov
Science for Life Laboratory, Department of Applied Physics; Institute of Translational Biomedicine
Хат алмасуға жауапты Автор.
Email: akkuratov.evgeny@gmail.com
Швеция, Stockholm; St. Petersburg, 199034
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