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Stimulation of Na,K-ATPase by Low Potassium Is Dependent on Transferrin

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Abstract

We took advantage of the fact that confluent MDCK cells can survive in a serum-free medium for several days to examine whether the upregulation of Na,K-ATPase by low K+ required serum. We found that serum was essential for low K+ to induce an increase in the cell surface Na,K-ATPase molecular number as quantified by ouabain binding assays. Further analyses identified that transferrin, not EGF or IGF-1, could simulate the effect of serum. Moreover, transferrin was also required for low-K+-induced increases in α1-subunit promoter activity, α1- and β1-subunit protein abundance of the Na,K-ATPase. In the presence of transferrin, low K+ enhanced cellular uptake of iron. Inhibition of intracellular iron activity by deferoxamine (40 µM) abrogated the effect of low K+ on the Na,K-ATPase. Like deferoxamine, catalase (100 U/ml) also ablated the effect of low K+. We conclude that stimulation of the Na,K-ATPase by low K+ is dependent on transferrin. The effect of transferrin is mediated by increased iron transport and reactive oxygen species activity.

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Acknowledgements

The authors thank Dr. Doug Fambrough (The Johns Hopkins University) and Dr. Maurice Burg (NIH) for their stimulating discussions during the course of this study. This study was supported by Uniformed Services University Grant RO83KA.

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Yin, W., Jiang, G., Takeyasu, K. et al. Stimulation of Na,K-ATPase by Low Potassium Is Dependent on Transferrin . J. Membrane Biol. 193, 177–184 (2003). https://doi.org/10.1007/s00232-003-2016-x

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