Glutathione is a low-affinity substrate of the human sodium-dependent dicarboxylate transporter

Nephron Physiol. 2013;124(1-2):1-5. doi: 10.1159/000356419. Epub 2013 Nov 14.

Abstract

Background/aims: During a single pass through the kidneys, more than 80% of glutathione (GSH) is excreted, indicating not only glomerular filtration, but also tubular secretion. The first step in tubular secretion is the uptake of a substance across the basolateral membrane of proximal tubule cells by sodium-dependent and -independent transporters. Due to the dicarboxylate-like structure, we postulated that GSH uptake across the basolateral membrane is mediated by the sodium-dependent dicarboxylate transporter 3 (NaDC3).

Methods: Tracer uptake and electrophysiologic measurements using a two-electrode voltage clamp device were performed in Xenopus laevis oocytes expressing the human (h)NaDC3.

Results: Uptake of succinate, the reference substrate of hNaDC3, was inhibited by GSH in a dose-dependent manner with an IC50 of 1.88 mM. GSH evoked potential-dependent inward currents, which were abolished under sodium-free conditions. At -60 mV, GSH currents showed saturation kinetics with a KM of 1.65 mM.

Conclusion: hNaDC3 present at the basolateral membrane of proximal tubule cells mediates sodium-dependent GSH uptake. The kinetic data show that NaDC3 is a low-affinity GSH transporter.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Glutathione / metabolism*
  • Humans
  • Kidney Tubules, Proximal / metabolism
  • Liver / metabolism
  • Oocytes / metabolism
  • Organic Anion Transporters, Sodium-Dependent / genetics
  • Organic Anion Transporters, Sodium-Dependent / metabolism*
  • RNA, Complementary / genetics
  • Succinic Acid / metabolism*
  • Symporters / genetics
  • Symporters / metabolism*
  • Xenopus laevis / genetics

Substances

  • Organic Anion Transporters, Sodium-Dependent
  • RNA, Complementary
  • SLC13A3 protein, human
  • Symporters
  • Succinic Acid
  • Glutathione