Тип публикации: статья из журнала

Год издания: 2001

Идентификатор DOI: 10.1046/j.1523-1755.2001.060002694.x

Ключевые слова: Na/Pi cotransport proteins, Lipid fluidity, membrane lipid dynamics, hypokalemia, glucosylceramide, ganglioside GM<sub>3</sub>, Brush-border membrane, proximal tubule

Аннотация: 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 V_max 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, <i>P</i> < 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.

Журнал: Kidney International

Выпуск журнала: Т. 60, № 2

Номера страниц: 694-704

ISSN журнала: 00852538

Издатель: John Wiley &amp; Sons

• Zajicek Hubert K. (Department of Internal Medicine, The University of Texas Southwestern Medical Center and VA Medical Center, Dallas, Texas, USA; Department of Physiology and Pharmacology, The University of Queensland, Brisbane, Queensland, Australia; Department of Internal Medicine, The University of Michigan Medical Center, Ann Arbor, Michigan, USA;&lt;br&gt;and Laboratoire d'Oncologie Moleculaire, Universite du Quebec a Montreal, Quebec, Canada)
• Wang Huamin (Department of Internal Medicine, The University of Texas Southwestern Medical Center and VA Medical Center, Dallas, Texas, USA; Department of Physiology and Pharmacology, The University of Queensland, Brisbane, Queensland, Australia; Department of Internal Medicine, The University of Michigan Medical Center, Ann Arbor, Michigan, USA;&lt;br&gt;and Laboratoire d'Oncologie Moleculaire, Universite du Quebec a Montreal, Quebec, Canada)
• Puttaparthi Krishna (Department of Internal Medicine, The University of Texas Southwestern Medical Center and VA Medical Center, Dallas, Texas, USA; Department of Physiology and Pharmacology, The University of Queensland, Brisbane, Queensland, Australia; Department of Internal Medicine, The University of Michigan Medical Center, Ann Arbor, Michigan, USA;&lt;br&gt;and Laboratoire d'Oncologie Moleculaire, Universite du Quebec a Montreal, Quebec, Canada)
• Halaihel Nabil (Department of Internal Medicine, The University of Texas Southwestern Medical Center and VA Medical Center, Dallas, Texas, USA; Department of Physiology and Pharmacology, The University of Queensland, Brisbane, Queensland, Australia; Department of Internal Medicine, The University of Michigan Medical Center, Ann Arbor, Michigan, USA;&lt;br&gt;and Laboratoire d'Oncologie Moleculaire, Universite du Quebec a Montreal, Quebec, Canada)
• Markovich Daniel (Department of Internal Medicine, The University of Texas Southwestern Medical Center and VA Medical Center, Dallas, Texas, USA; Department of Physiology and Pharmacology, The University of Queensland, Brisbane, Queensland, Australia; Department of Internal Medicine, The University of Michigan Medical Center, Ann Arbor, Michigan, USA;&lt;br&gt;and Laboratoire d'Oncologie Moleculaire, Universite du Quebec a Montreal, Quebec, Canada)
• Shayman James (Department of Internal Medicine, The University of Texas Southwestern Medical Center and VA Medical Center, Dallas, Texas, USA; Department of Physiology and Pharmacology, The University of Queensland, Brisbane, Queensland, Australia; Department of Internal Medicine, The University of Michigan Medical Center, Ann Arbor, Michigan, USA;&lt;br&gt;and Laboratoire d'Oncologie Moleculaire, Universite du Quebec a Montreal, Quebec, Canada)
• Beliveau Richard (Department of Internal Medicine, The University of Texas Southwestern Medical Center and VA Medical Center, Dallas, Texas, USA; Department of Physiology and Pharmacology, The University of Queensland, Brisbane, Queensland, Australia; Department of Internal Medicine, The University of Michigan Medical Center, Ann Arbor, Michigan, USA;&lt;br&gt;and Laboratoire d'Oncologie Moleculaire, Universite du Quebec a Montreal, Quebec, Canada)
• Wilson Paul (Department of Internal Medicine, The University of Texas Southwestern Medical Center and VA Medical Center, Dallas, Texas, USA; Department of Physiology and Pharmacology, The University of Queensland, Brisbane, Queensland, Australia; Department of Internal Medicine, The University of Michigan Medical Center, Ann Arbor, Michigan, USA;&lt;br&gt;and Laboratoire d'Oncologie Moleculaire, Universite du Quebec a Montreal, Quebec, Canada)
• Rogers Thomas (Department of Internal Medicine, The University of Texas Southwestern Medical Center and VA Medical Center, Dallas, Texas, USA; Department of Physiology and Pharmacology, The University of Queensland, Brisbane, Queensland, Australia; Department of Internal Medicine, The University of Michigan Medical Center, Ann Arbor, Michigan, USA;&lt;br&gt;and Laboratoire d'Oncologie Moleculaire, Universite du Quebec a Montreal, Quebec, Canada)
• Levi Moshe (Department of Internal Medicine, The University of Texas Southwestern Medical Center and VA Medical Center, Dallas, Texas, USA; Department of Physiology and Pharmacology, The University of Queensland, Brisbane, Queensland, Australia; Department of Internal Medicine, The University of Michigan Medical Center, Ann Arbor, Michigan, USA;&lt;br&gt;and Laboratoire d'Oncologie Moleculaire, Universite du Quebec a Montreal, Quebec, Canada)

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