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PubMed2005

Cardiac glycosides inhibit TNF-alpha/NF-kappaB signaling by blocking recruitment of TNF receptor-associated death domain to the TNF receptor.

Digitoxin and structurally related cardiac glycoside drugs potently block activation of the TNF-alpha/NF-kappaB signaling pathway. We have hypothesized that the mechanism might be discovered by searching systematically for selective inhibitory action through the entire pathway. We report that the common action of these drugs is to block the TNF-alpha-dependent binding of TNF receptor 1 to TNF receptor-associated death domain. This drug action can be observed with native cells, such as HeLa, and reconstituted systems prepared in HEK293 cells. All other antiinflammatory effects of digitoxin on NF-kappaB and c-Jun N-terminal kinase pathways appear to follow from the blockade of this initial upstream signaling event.

Blotting, Western↗
PubMed1956

Cardiac glycosides.

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Cardiac Glycosides↗
PubMed1990

The toxic effects on cardiac myocytes of tyledoside F, a cumulative neurotoxic cardiac glycoside isolated from Tylecodon grandiflorus.

To investigate the cardiac cellular effects of tyledoside F, a cumulative neurotoxic bufadienolide and ouabain, a non-cumulative cardenolide, the whole-cell clamp method was used to measure the Na-K pump current after the Na-K pump had been activated by high intracellular Na2+. The toxic effects of tyledoside F and ouabain on cardiac myocytes were also investigated by observing the effect of the Ca2+ overload on the variability of myocytes during a period of 75 min. From the results it is clear that there are similarities in the direct effects of tyledoside F and ouabain on the Na-K pump. It was found that ouabain inhibited the Na-K pump current more than that of tyledoside F. With regard to Ca2+ overload, there are differences in their mode of production of Ca2+ overload because cinnarizine protects the myocytes against ouabain-induced Ca2+ overload but not against tyledoside-induced Ca2+ overload. This study shows that with the whole-cell clamp technique tyledoside F inhibited the Na-K pump in a manner similar to inhibition of the pump by ouabain. Viability studies with myocytes indicated that tyledoside F also has other effects which are different from these of ouabain.

Animals↗
PubMed1983

Krimpsiekte and acute cardiac glycoside poisoning in sheep caused by bufadienolides from the plant Kalanchoe lanceolata Forsk.

Three toxic bufadienolides , one characterized as hellibrigenin 3-acetate, have been isolated from Kalanchoe lanceolata Forsk. Typical signs of cardiac glycoside poisoning, involving the gastro-intestinal, neuromuscular and cardiovascular systems, could be induced by drenching the milled plant to sheep. Such signs could also be induced by dosing the bufadienolides to sheep or by injecting them into both guinea-pigs (subcutaneously) and sheep (intravenously). The specific paretic syndrome, krimpsiekte , on the other hand, was reproduced only by the repeated intravenous administration of smaller doses of the 2 unknown bufadienolides to sheep. Histopathological examination revealed a mild to severe multifocal cardiomyopathy in sheep receiving plant material or bufadienolides .

Acute Disease↗