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This Article Full Text Full Text (PDF) Data Supplement Ouabain rescues from renal apoptosis via activation of NF-kappaB All Versions of this Article: ASN.2005080894v1 17/7/1848    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Li, J. Articles by Aizman, O. Search for Related Content PubMed PubMed Citation Articles by Li, J. Articles by Aizman, O. Related Collections Related Article

Low Doses of Ouabain Protect from Serum Deprivation–Triggered Apoptosis and Stimulate Kidney Cell Proliferation via Activation of NF-B

Karolinska Institutet, Department of Woman and Child Health, Astrid Lindgren Children’s Hospital, Stockholm, Sweden

Address correspondence to: Dr. Oleg Aizman, Karolinska Institutet, Astrid Lindgren Children’s Hospital, Q2:09, SE-171 76 Stockholm, Sweden. Phone: +46-08-51777375; Fax: +46-08-51777328; E-mail: oleg.aizman{at}kbh.ki.se.

Received for publication August 31, 2005. Accepted for publication April 10, 2006.

It now generally is agreed that Na,K-ATPase, in addition to its role in the maintenance of Na⁺ and K⁺ gradients across the cell membrane, plays a role in communicating information from the extracellular environment to intracellular signaling pathways. It was reported recently that interaction between ouabain-bound Na,K-ATPase and the 1,4,5-trisphosphate receptor (IP₃R) triggers slow calcium oscillations and activation of NF-B. Here it is demonstrated that this signaling pathway can serve to prevent cell death and promote cell growth. Rat renal proximal tubular cells in primary culture first were grown in the presence of 10% serum and then exposed to 0.2% serum for 24 h to induce apoptosis. Serum starvation increased the apoptotic index from 1.21 ± 0.26 to 14.01 ± 1.17%. Ouabain in concentrations that did not inhibit Na,K-ATPase activity (1 to 10 nM) completely abolished the apoptotic effect of serum starvation. Ouabain protection from apoptosis was not observed when release of calcium from intracellular stores via the IP₃R was prevented. It was shown that the NH₂ terminal tail of the Na,K-ATPase subunit plays a key role in ouabain-triggered calcium oscillations. It was found that ouabain did not protect from apoptosis in serum-deprived cells that expressed a mutant Na,K-ATPase subunit with deletion of the NH₂ terminal tail. Ouabain exposure (10 nM for 24 h) significantly increased translocation of NF-B from cytoplasm to nucleus. Helenalin, an inhibitor of NF-B, abolished the antiapoptotic effect of ouabain. Ouabain (0.1 to 10 nM) also was found to stimulate proliferation and increase the viability of kidney cells. These effects were abolished when release of calcium via the IP₃R was prevented.

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