NRF2 regulates the glutamine transporter Slc38a3 (SNAT3) in kidney in response to metabolic acidosis.
- Lister A Department of Pharmaceutical Sciences, Division of Molecular and Systems Toxicology, University of Basel, Klingelbergstrasse 50, 4056, Basel, Switzerland.
- Bourgeois S Institute of Physiology, Zürich Centre for Integrative Human Physiology, University of Zürich, Winterthurerstrasse 190, 8057, Zürich, Switzerland.
- Imenez Silva PH Institute of Physiology, Zürich Centre for Integrative Human Physiology, University of Zürich, Winterthurerstrasse 190, 8057, Zürich, Switzerland.
- Rubio-Aliaga I Institute of Physiology, Zürich Centre for Integrative Human Physiology, University of Zürich, Winterthurerstrasse 190, 8057, Zürich, Switzerland.
- Marbet P Department of Pharmaceutical Sciences, Division of Molecular and Systems Toxicology, University of Basel, Klingelbergstrasse 50, 4056, Basel, Switzerland.
- Walsh J Department of Molecular and Clinical Pharmacology, MRC Centre for Drug Safety Science, University of Liverpool, Liverpool, L69 3GE, UK.
- Shelton LM Department of Molecular and Clinical Pharmacology, MRC Centre for Drug Safety Science, University of Liverpool, Liverpool, L69 3GE, UK.
- Keller B Institute of Physiology, Zürich Centre for Integrative Human Physiology, University of Zürich, Winterthurerstrasse 190, 8057, Zürich, Switzerland.
- Verrey F Institute of Physiology, Zürich Centre for Integrative Human Physiology, University of Zürich, Winterthurerstrasse 190, 8057, Zürich, Switzerland.
- Devuyst O Institute of Physiology, Zürich Centre for Integrative Human Physiology, University of Zürich, Winterthurerstrasse 190, 8057, Zürich, Switzerland.
- Giesbertz P Department of Biochemistry, ZIEL Research Center of Nutrition and Food Sciences, Technische Universität München, Freising, Germany.
- Daniel H Department of Biochemistry, ZIEL Research Center of Nutrition and Food Sciences, Technische Universität München, Freising, Germany.
- Goldring CE Department of Molecular and Clinical Pharmacology, MRC Centre for Drug Safety Science, University of Liverpool, Liverpool, L69 3GE, UK.
- Copple IM Department of Molecular and Clinical Pharmacology, MRC Centre for Drug Safety Science, University of Liverpool, Liverpool, L69 3GE, UK.
- Wagner CA Institute of Physiology, Zürich Centre for Integrative Human Physiology, University of Zürich, Winterthurerstrasse 190, 8057, Zürich, Switzerland. Wagnerca@access.uzh.ch.
- Odermatt A Department of Pharmaceutical Sciences, Division of Molecular and Systems Toxicology, University of Basel, Klingelbergstrasse 50, 4056, Basel, Switzerland. alex.odermatt@unibas.ch.
- 2018-04-06
Published in:
- Scientific reports. - 2018
Acidosis
Amino Acid Transport Systems, Neutral
Amino Acids
Animals
Glutathione
Kidney Tubules
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
NF-E2-Related Factor 2
English
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.
- Language
-
- English
- Open access status
- gold
- Identifiers
-
- DOI 10.1038/s41598-018-24000-2
- PMID 29618784
- Persistent URL
- https://sonar.ch/global/documents/191441
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