Effect of NBCe1 deletion on renal citrate and 2-oxoglutarate handling

Gunars Osis, Mary E. Handlogten, Hyun Wook Lee, Kathleen S. Hering-Smith, Weitao Huang, Michael F. Romero, Jill W. Verlander, I. David Weiner

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

The bicarbonate transporter, NBCe1 (SLC4A4), is necessary for at least two components of the proximal tubule contribution to acid-base homeostasis, filtered bicarbonate reabsorption, and ammonia metabolism. This study's purpose was to determine NBCe1's role in a third component of acid-base homeostasis, organic anion metabolism, by studying mice with NBCe1 deletion. Because NBCe1 deletion causes metabolic acidosis, we also examined acid-loaded wild-type adult mice to determine if the effects of NBCe1 deletion were specific to NBCe1 deletion or were a non-specific effect of the associated metabolic acidosis. Both NBCe1 KO and acid-loading decreased citrate excretion, but in contrast to metabolic acidosis alone, NBCe1 KO decreased expression of the apical citrate transporter, NaDC-1. Thus, NBCe1 expression is necessary for normal NaDC-1 expression, and NBCe1 deletion induces a novel citrate reabsorptive pathway. Second, NBCe1 KO increased 2-oxoglutarate excretion. This could not be attributed to the metabolic acidosis as experimental acidosis decreased excretion. Increased 2-oxoglutarate excretion could not be explained by changes in plasma 2-oxoglutarate levels, the glutaminase I or the glutaminase II generation pathways, 2-oxoglutarate metabolism, its putative apical 2-oxoglutarate transporter, OAT10, or its basolateral transporter, NaDC-3. In summary: (1) NBCe1 is necessary for normal proximal tubule NaDC-1 expression; (2) NBCe1 deletion results in stimulation of a novel citrate reabsorptive pathway; and (3) NBCe1 is necessary for normal 2-oxoglutarate metabolism through mechanisms independent of expression of known transport and metabolic pathways.

Original languageEnglish (US)
Article numbere12778
JournalPhysiological reports
Volume4
Issue number8
DOIs
StatePublished - Apr 1 2016

Keywords

  • 2-oxoglutarate
  • Acidosis
  • Citrate
  • NBCe1
  • NaDC-1
  • Proximal tubule

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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