Ouabain, a steroid hormone that signals with slow calcium oscillations
2001 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 98, no 23, 13420-13424 p.Article in journal (Refereed) Published
The plant-derived steroid, digoxin, a specific inhibitor of Na,K-ATPase, has been used for centuries in the treatment of heart disease. Recent studies demonstrate the presence of a digoxin analog, ouabain, in mammalian tissue, but its biological role has not been elucidated. Here, we show in renal epithelial cells that ouabain, in doses causing only partial Na,K-ATPase inhibition, acts as a biological inducer of regular, low-frequency intracellular calcium ([Ca2+](i)) oscillations that elicit activation of the transcription factor, NF-KB. Partial inhibition of Na,K-ATPase using low extracellular K+ and depolarization of cells did not have these effects. Incubation of cells in Ca2+-free media, inhibition of voltage-gated calcium channels, inositol triphosphate receptor antagonism, and redistribution of actin to a thick layer adjacent to the plasma membrane abolished [Ca2+](i) oscillations, indicating that they were caused by a concerted action of inositol triphosphate receptors and capacitative calcium entry via plasma membrane channels. Blockade of ouabain-induced [C-a2+](i) oscillations prevented activation of NF-kappaB. The results demonstrate a new mechanism for steroid signaling via plasma membrane receptors and underline a novel role for the steroid hormone, ouabain, as a physiological inducer of [Ca2+](i) oscillations involved in transcriptional regulation in mammalian cells.
Place, publisher, year, edition, pages
2001. Vol. 98, no 23, 13420-13424 p.
nf-kappa-b, cardiac myocytes, na+/k+-atpase, endogenous ouabain, gene-expression, inositol trisphosphate, transcription factor, ca2+ oscillations, response genes, plasma
IdentifiersURN: urn:nbn:se:kth:diva-21083ISI: 000172076800105OAI: oai:DiVA.org:kth-21083DiVA: diva2:339780
QC 201005252010-08-102010-08-10Bibliographically approved