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

Autor:	Philippe Marbet, Bettina Keller, Isabel Rubio-Aliaga, Carsten A. Wagner, Olivier Devuyst, Alex Odermatt, Hannelore Daniel, Christopher E. Goldring, Pieter Giesbertz, Joanne Walsh, Luke M. Shelton, Ian M. Copple, François Verrey, Pedro Henrique Imenez Silva, Adam Lister, Soline Bourgeois
Přispěvatelé:	University of Zurich, Wagner, Carsten A
Jazyk:	angličtina
Rok vydání:	2018
Předmět:	Male 0301 basic medicine medicine.medical_specialty NF-E2-Related Factor 2 chemistry.chemical_element lcsh:Medicine 610 Medicine & health Calcium medicine.disease_cause environment and public health Article 10052 Institute of Physiology Mice 03 medical and health sciences Internal medicine medicine Animals Amino Acids lcsh:Science Acidosis Mice Knockout chemistry.chemical_classification Kidney 1000 Multidisciplinary Multidisciplinary lcsh:R Metabolic acidosis Transporter respiratory system medicine.disease Glutathione Mice Inbred C57BL Glutamine Amino Acid Transport Systems Neutral Kidney Tubules 030104 developmental biology Endocrinology medicine.anatomical_structure Enzyme chemistry 10076 Center for Integrative Human Physiology 570 Life sciences biology lcsh:Q medicine.symptom Oxidative stress
Zdroj:	Scientific Reports, Vol 8, Iss 1, Pp 1-13 (2018) Scientific Reports
ISSN:	2045-2322
DOI:	10.1038/s41598-018-24000-2
Popis:	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.
Databáze:	OpenAIRE
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