Stimulation of Na,K-ATPase by low potassium is dependent on transferrin.
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 al-subunit promoter activity, al- and el-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 microM) 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.
Yin
W
W
Department of Medicine, Uniformed Services University of the Health Sciences, 4301, Jones Bridge Rd, Bethesda, MD 20814, USA.
Jiang
G
G
Takeyasu
K
K
Zhou
X
X
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects / Q000502:physiology; D032701:Biomimetics / Q000379:methods; D002374:Catalase / Q000494:pharmacology; D002478:Cells, Cultured; D003470:Culture Media / Q000378:metabolism*; D003676:Deferoxamine / Q000494:pharmacology; D004285:Dogs; D004789:Enzyme Activation / Q000187:drug effects; D007501:Iron / Q000493:pharmacokinetics*; D007668:Kidney / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism*; D044967:Serum / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects / Q000378:metabolism*; D014168:Transferrin / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D003470:Culture Media; D014168:Transferrin; D007501:Iron; D002374:Catalase; D000254:Sodium-Potassium-Exchanging ATPase; D003676:Deferoxamine; D011188:Potassium