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- Title
Glycosphingolipids modulate renal phosphate transport in potassium deficiency.
- Authors
Zajicek, Hubert K.; Wang, Huamin; Puttaparthi, Krishna; Halaihel, Nabil; Markovich, Daniel; Shayman, James; Béliveau, Richard; Wilson, Paul; Rogers, Thomas; Levi, Moshe
- Abstract
Glycosphingolipids modulate renal phosphate transport in potassium deficiency. Background. Potassium (K) deficiency (KD) and/or hypokalemia have been associated with disturbances of phosphate metabolism. The purpose of the present study was to determine the cellular mechanisms that mediate the impairment of renal proximal tubular Na/Pi cotransport in a model of K deficiency in the rat. Methods. K deficiency in the rat was achieved by feeding rats a K-deficient diet for seven days, which resulted in a marked decrease in serum and tissue K content. Results. K deficiency resulted in a marked increase in urinary Pi excretion and a decrease in the Vmax of brush-border membrane (BBM) Na/Pi cotransport activity (1943 ± 95 in control vs. 1184 ± 99 pmol/5 sec/mg BBM protein in K deficiency, P < 0.02). Surprisingly, the decrease in Na/Pi cotransport activity was associated with increases in the abundance of type I (NaPi-1), and type II (NaPi-2) and type III (Glvr-1) Na/Pi protein. The decrease in Na/Pi transport was associated with significant alterations in BBM lipid composition, including increases in sphingomyelin, glucosylceramide, and ganglioside GM3 content and a decrease in BBM lipid fluidity. Inhibition of glucosylceramide synthesis resulted in increases in BBM Na/Pi cotransport activity in control and K-deficient rats. The resultant Na/Pi cotransport activity in K-deficient rats was the same as in control rats (1148 ± 52 in control + PDMP vs. 1152 ± 61 pmol/5 sec/mg BBM protein in K deficiency + PDMP). These changes in transport activity occurred independent of further changes in BBM NaPi-2 protein or renal cortical NaPi-2 mRNA abundance. Conclusion. K deficiency in the rat causes inhibition of renal Na/Pi cotransport activity by post-translational mechanisms that are mediated in part through alterations in glucosylceramide content and membrane lipid dynamics.
- Subjects
GLYCOSPHINGOLIPIDS; PHOSPHATES; POTASSIUM deficiency diseases
- Publication
Kidney International, 2001, Vol 60, Issue 2, p694
- ISSN
0085-2538
- Publication type
Article
- DOI
10.1046/j.1523-1755.2001.060002694.x