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• W2134927237 endingPage "1857" @default.
• W2134927237 startingPage "1848" @default.
• W2134927237 abstract "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-κB. 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 <i>via</i> the IP₃R was prevented. It was shown that the NH₂ terminal tail of the Na,K-ATPase α 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 α subunit with deletion of the NH₂ terminal tail. Ouabain exposure (10 nM for 24 h) significantly increased translocation of NF-κB from cytoplasm to nucleus. Helenalin, an inhibitor of NF-κB, 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 <i>via</i> the IP₃R was prevented." @default.
• W2134927237 created "2016-06-24" @default.
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• W2134927237 date "2006-07-01" @default.
• W2134927237 modified "2023-10-08" @default.
• W2134927237 title "Low Doses of Ouabain Protect from Serum Deprivation–Triggered Apoptosis and Stimulate Kidney Cell Proliferation via Activation of NF-κB" @default.
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• W2134927237 doi "https://doi.org/10.1681/asn.2005080894" @default.
• W2134927237 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/16707566" @default.
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