Dexamethasone modulates rat renal brush border membrane phosphate transporter mRNA and protein abundance and glycosphingolipid composition

M. Levi, J. A. Shayman, A. Abe, S. K. Gross, R. H. McCluer, J. Biber, H. Murer, M. Lotscher, R. E. Cronin

Research output: Contribution to journalArticle

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Abstract

Glucocorticoids are important regulators of renal phosphate transport. This study investigates the role of alterations in renal brush border membrane (BBM) sodium gradient-dependent phosphate transport (Na-Pi cotransporter) mRNA and protein abundance in the dexamethasone induced inhibition of Na-Pi cotransport in the rat. Dexamethasone administration for 4 d caused a 1.5-fold increase in the V(max) of Na-Pi cotransport (1785±119 vs. 2759±375 pmol/5 s per mg BBM protein in control, P < 0.01), which was paralleled by a 2.5-fold decrease in the abundance of Na-Pi mRNA and Na-Pi protein. There was also a 1.7-fold increase in BBM glucosylceramide content (528±63 vs. 312±41 ng/mg BBM protein in control, P < 0.02). To determine whether the alteration in glucosylceramide content per se played a functional role in the decrease in Na-Pi cotransport, control rats were treated with the glucosylceramide synthase inhibitor, D-threo-1-phenyl-2-decanoyl-amino-3- morpholino-1-propanol (PDMP). The resultant 1.5-fold decrease in BBM glucosylceramide content (199±19 vs. 312±41 ng/mg BBM protein in control, P < 0.02) was associated with a 1.4-fold increase in Na-Pi cotransport activity (1422±73 vs. 1048±85 pmol/5 s per mg BBM protein in control, P < 0.01), and a 1.5-fold increase in BBM Na-Pi protein abundance. Thus, dexamethasone- induced inhibition of Na-Pi cotransport is associated with a decrease in BBM Na-Pi cotransporter abundance, and an increase in glucosylceramide. Since primary alteration in BBM glucosylceramide content per se directly and selectively modulates BBM Na-Pi cotransport activity and Na-Pi protein abundance, we propose that the increase in BBM glucosylceramide content plays an important role in mediating the inhibitory effect of dexamethasone on Na- Pi cotransport activity.

Original languageEnglish (US)
Pages (from-to)207-216
Number of pages10
JournalJournal of Clinical Investigation
Volume96
Issue number1
StatePublished - 1995

Fingerprint

Phosphate Transport Proteins
Glycosphingolipids
Membrane Transport Proteins
Microvilli
Dexamethasone
Glucosylceramides
Kidney
Messenger RNA
Proteins
Membranes
Membrane Proteins
ceramide glucosyltransferase
Phosphates
Morpholinos
Glycogen Synthase
Glucocorticoids

Keywords

  • glucocorticoids
  • glucosylceramide
  • membrane fluidity
  • NaPi-2 protein
  • sphingomyelin

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Levi, M., Shayman, J. A., Abe, A., Gross, S. K., McCluer, R. H., Biber, J., ... Cronin, R. E. (1995). Dexamethasone modulates rat renal brush border membrane phosphate transporter mRNA and protein abundance and glycosphingolipid composition. Journal of Clinical Investigation, 96(1), 207-216.

Dexamethasone modulates rat renal brush border membrane phosphate transporter mRNA and protein abundance and glycosphingolipid composition. / Levi, M.; Shayman, J. A.; Abe, A.; Gross, S. K.; McCluer, R. H.; Biber, J.; Murer, H.; Lotscher, M.; Cronin, R. E.

In: Journal of Clinical Investigation, Vol. 96, No. 1, 1995, p. 207-216.

Research output: Contribution to journalArticle

Levi, M, Shayman, JA, Abe, A, Gross, SK, McCluer, RH, Biber, J, Murer, H, Lotscher, M & Cronin, RE 1995, 'Dexamethasone modulates rat renal brush border membrane phosphate transporter mRNA and protein abundance and glycosphingolipid composition', Journal of Clinical Investigation, vol. 96, no. 1, pp. 207-216.
Levi, M. ; Shayman, J. A. ; Abe, A. ; Gross, S. K. ; McCluer, R. H. ; Biber, J. ; Murer, H. ; Lotscher, M. ; Cronin, R. E. / Dexamethasone modulates rat renal brush border membrane phosphate transporter mRNA and protein abundance and glycosphingolipid composition. In: Journal of Clinical Investigation. 1995 ; Vol. 96, No. 1. pp. 207-216.
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abstract = "Glucocorticoids are important regulators of renal phosphate transport. This study investigates the role of alterations in renal brush border membrane (BBM) sodium gradient-dependent phosphate transport (Na-Pi cotransporter) mRNA and protein abundance in the dexamethasone induced inhibition of Na-Pi cotransport in the rat. Dexamethasone administration for 4 d caused a 1.5-fold increase in the V(max) of Na-Pi cotransport (1785±119 vs. 2759±375 pmol/5 s per mg BBM protein in control, P < 0.01), which was paralleled by a 2.5-fold decrease in the abundance of Na-Pi mRNA and Na-Pi protein. There was also a 1.7-fold increase in BBM glucosylceramide content (528±63 vs. 312±41 ng/mg BBM protein in control, P < 0.02). To determine whether the alteration in glucosylceramide content per se played a functional role in the decrease in Na-Pi cotransport, control rats were treated with the glucosylceramide synthase inhibitor, D-threo-1-phenyl-2-decanoyl-amino-3- morpholino-1-propanol (PDMP). The resultant 1.5-fold decrease in BBM glucosylceramide content (199±19 vs. 312±41 ng/mg BBM protein in control, P < 0.02) was associated with a 1.4-fold increase in Na-Pi cotransport activity (1422±73 vs. 1048±85 pmol/5 s per mg BBM protein in control, P < 0.01), and a 1.5-fold increase in BBM Na-Pi protein abundance. Thus, dexamethasone- induced inhibition of Na-Pi cotransport is associated with a decrease in BBM Na-Pi cotransporter abundance, and an increase in glucosylceramide. Since primary alteration in BBM glucosylceramide content per se directly and selectively modulates BBM Na-Pi cotransport activity and Na-Pi protein abundance, we propose that the increase in BBM glucosylceramide content plays an important role in mediating the inhibitory effect of dexamethasone on Na- Pi cotransport activity.",
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AU - Biber, J.

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N2 - Glucocorticoids are important regulators of renal phosphate transport. This study investigates the role of alterations in renal brush border membrane (BBM) sodium gradient-dependent phosphate transport (Na-Pi cotransporter) mRNA and protein abundance in the dexamethasone induced inhibition of Na-Pi cotransport in the rat. Dexamethasone administration for 4 d caused a 1.5-fold increase in the V(max) of Na-Pi cotransport (1785±119 vs. 2759±375 pmol/5 s per mg BBM protein in control, P < 0.01), which was paralleled by a 2.5-fold decrease in the abundance of Na-Pi mRNA and Na-Pi protein. There was also a 1.7-fold increase in BBM glucosylceramide content (528±63 vs. 312±41 ng/mg BBM protein in control, P < 0.02). To determine whether the alteration in glucosylceramide content per se played a functional role in the decrease in Na-Pi cotransport, control rats were treated with the glucosylceramide synthase inhibitor, D-threo-1-phenyl-2-decanoyl-amino-3- morpholino-1-propanol (PDMP). The resultant 1.5-fold decrease in BBM glucosylceramide content (199±19 vs. 312±41 ng/mg BBM protein in control, P < 0.02) was associated with a 1.4-fold increase in Na-Pi cotransport activity (1422±73 vs. 1048±85 pmol/5 s per mg BBM protein in control, P < 0.01), and a 1.5-fold increase in BBM Na-Pi protein abundance. Thus, dexamethasone- induced inhibition of Na-Pi cotransport is associated with a decrease in BBM Na-Pi cotransporter abundance, and an increase in glucosylceramide. Since primary alteration in BBM glucosylceramide content per se directly and selectively modulates BBM Na-Pi cotransport activity and Na-Pi protein abundance, we propose that the increase in BBM glucosylceramide content plays an important role in mediating the inhibitory effect of dexamethasone on Na- Pi cotransport activity.

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