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NRF2 regulates the glutamine transporter Slc38a3 (SNAT3) in kidney in response to metabolic acidosis.

ABSTRACT: Expression of the glutamine transporter SNAT3 increases in kidney during metabolic acidosis, suggesting a role during ammoniagenesis. Microarray analysis of Nrf2 knock-out (KO) mouse kidney identified Snat3 as the most significantly down-regulated transcript compared to wild-type (WT). We hypothesized that in the absence of NRF2 the kidney would be unable to induce SNAT3 under conditions of metabolic acidosis and therefore reduce the availability of glutamine for ammoniagenesis. Metabolic acidosis was induced for 7 days in WT and Nrf2 KO mice. Nrf2 KO mice failed to induce Snat3 mRNA and protein expression during metabolic acidosis. However, there were no differences in blood pH, bicarbonate, pCO2, chloride and calcium or urinary pH, ammonium and phosphate levels. Normal induction of ammoniagenic enzymes was observed whereas several amino acid transporters showed differential regulation. Moreover, Nrf2 KO mice during acidosis showed increased expression of renal markers of oxidative stress and injury and NRF2 activity was increased during metabolic acidosis in WT kidney. We conclude that NRF2 is required to adapt the levels of SNAT3 in response to metabolic acidosis. In the absence of NRF2 and SNAT3, the kidney does not have any major acid handling defect; however, increased oxidative stress and renal injury may occur.

SUBMITTER: Lister A

PROVIDER: S-EPMC5884861 | biostudies-other | 2018 Apr

REPOSITORIES: biostudies-other

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NRF2 regulates the glutamine transporter Slc38a3 (SNAT3) in kidney in response to metabolic acidosis.

Lister Adam A Bourgeois Soline S Imenez Silva Pedro H PH Rubio-Aliaga Isabel I Marbet Philippe P Walsh Joanne J Shelton Luke M LM Keller Bettina B Verrey Francois F Devuyst Olivier O Giesbertz Pieter P Daniel Hannelore H Goldring Christopher E CE Copple Ian M IM Wagner Carsten A CA Odermatt Alex A

Scientific reports 20180404 1

Expression of the glutamine transporter SNAT3 increases in kidney during metabolic acidosis, suggesting a role during ammoniagenesis. Microarray analysis of Nrf2 knock-out (KO) mouse kidney identified Snat3 as the most significantly down-regulated transcript compared to wild-type (WT). We hypothesized that in the absence of NRF2 the kidney would be unable to induce SNAT3 under conditions of metabolic acidosis and therefore reduce the availability of glutamine for ammoniagenesis. Metabolic acidos ...[more]

PMID: 29618784

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Dataset Information

NRF2 regulates the glutamine transporter Slc38a3 (SNAT3) in kidney in response to metabolic acidosis.

Publications

NRF2 regulates the glutamine transporter Slc38a3 (SNAT3) in kidney in response to metabolic acidosis.

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