Cellular mechanisms involved in the acute adaptation of OK cell Na/P(i)-cotransport to high- or low-P(i) medium

Markus F. Pfister, Helene Hilfiker, Judith Forgo, Eleanor Lederer, Jürg Biber, Heini Murer

Research output: Contribution to journalArticlepeer-review

64 Scopus citations

Abstract

Variations in dietary phosphate (P(i)) intake in rats lend to alterations of renal P(i) reabsorption. These effects are associated with corresponding changes in the abundance of the type II Na/P(i)-cotransporter protein in proximal tubular brush-border membranes. In the present study we investigated the regulation of the type II Na/P(i)-cotransporter in response to high- and low-P(i) medium in opossum kidney (OK) cells, an epithelial cell-line of proximal tubular origin. We show that 'acute' (4 h) and 'chronic' (24 h) exposures of OK cells to high- or low-P(i) medium lead to decreases or increases, respectively, in Na/P(i)-cotransport activity which are paralleled by alterations in the total cellular amount of the corresponding type II Na/P(i)-cotransporter protein (NaPi-4), but not by changes in the amount of the NaPi-4 mRNA. Also in OK cells transfected with the corresponding rat renal type II Na/P(i)-cotransporter (NaPi-2) alterations in the P(i) concentration in the medium lend to changes in the amount of NaPi-2 protein but not in the amount of NaPi-2 mRNA. Furthermore we show that lysosomal inhibitors prevent the degradation of the transporter, but do not interfere with its inhibition, in response to 'acute' exposure of OK cells to high-P(i) medium. Inhibition of lysosomal degradation also leads, in control conditions, to an accumulation of the transporter detectable on Western blot. It is concluded that the lysosomal proteolytic pathway is not only involved in the P(i)-induced downregulation of the type II Na/P(i)-cotransporter but also in its basic turnover.

Original languageEnglish (US)
Pages (from-to)713-719
Number of pages7
JournalPflugers Archiv European Journal of Physiology
Volume435
Issue number5
DOIs
StatePublished - Mar 18 1998
Externally publishedYes

Keywords

  • Lysosomal degradation
  • Na/P(i)-cotransporter P(i)-adaptation
  • Opossum kidney (OK) cells
  • Renal type II

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Physiology (medical)

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