Cardiac glycosides with target at direct and indirect interactions with nuclear receptors - 30/05/20
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Graphical abstract |
Highlights |
• | Natural-origin cardiac glycosides were historically used in heart failure treatment. |
• | Their direct and indirect targets can be nuclear receptors (transcription factors). |
• | Cardiac glycosides act directly through binding to nuclear receptors as ligands. |
• | Indirect effects include changes in cellular signaling. |
• | Cardiac glycosides affect hormonal management, immune processes, and carcinogenesis. |
Abstract |
Cardiac glycosides are compounds isolated from plants and animals and have been known since ancient times. These compounds inhibit the activity of the sodium potassium pump in eukaryotic cells. Cardiac glycosides were used as drugs in heart ailments to increase myocardial contraction force and, at the same time, to lower frequency of this contraction. An increasing number of studies have indicated that the biological effects of these compounds are not limited to inhibition of sodium-potassium pump activity. Furthermore, an increasing number of data have shown that they are synthesized in tissues of mammals, where they may act as a new class of steroid hormones or other hormones by mimicry to modulate various signaling pathways and influence whole organisms. Thus, we discuss the interactions of cardiac glycosides with the nuclear receptor superfamily of transcription factors activated by low-weight molecular ligands (including hormones) that regulate many functions of cells and organisms. Cardiac glycosides of endogenous and exogenous origin by interacting with nuclear receptors can affect the processes regulated by these transcription factors, including hormonal management, immune system, body defense, and carcinogenesis. They can also be treated as initial structures for combinatorial chemistry to produce new compounds (including drugs) with the desired properties.
Le texte complet de cet article est disponible en PDF.Abbreviations : ABCA1, AF, AHR, AR, CAR, CCR4, CCR6, CD, CGBG, Cyp8b1, DBD, EAE, Elovl3, EMSA, ER, ERK1/2, G6PC, GM-CSF, GR, HNF4, IL17A, IL17 F, IL21, IL22, IL23R, INFγ, Insig2a, IRF4, LBD, LXR, MR, MS, NCOA1, NGFIB, NPAS2, NR, P450scc, PMA, PPAR, PR, PXR, RA, RAR, RE, RORγ, RORγT, SF1, StAR, TR, VDR
Keywords : Cardiac glycoside, Nuclear receptor, Digoxin, Ouabain
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Vol 127
Article 110106- juillet 2020 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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