Regulation of cytosolic pH and lactic acid release in mesangial cells overexpressing GLUT1

Karl S. Lang, Matthias M. Mueller, Valerie Tanneur, Sabine Wallisch, Olga Fedorenko, Monica Palmada, Florian Lang, Stefan Bröer, Charles W. Heilig, Erwin Schleicher, Cora Weigert

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4 Citations (Scopus)

Abstract

Background. Anaerobic glycolysis leads to the formation of lactate and H+ and thus imposes a significant challenge on cytosolic acid/base regulation. Cytosolic acidification, on the other hand, is known to inhibit flux through glycolysis and lactate formation. To explore the interplay of cytosolic pH and glycolysis, rat mesangial cells transfected with the glucose transporter GLUT1 (GLUT1 cells) were compared with those transfected with β-galactosidase (LacZ cells). Methods. In the presence of extracellular glucose, the glycolytic rate was one order of magnitude higher in GLUT1 cells than in LacZ cells. Cytosolic pH (pHi) was significantly higher in GLUT1 than LacZ cells, an effect abolished in the presence of Na +/H+ exchange inhibitor ethylisopropylamiloride (1 μmol/L). Results. Addition of 40 mmol/L lactate led to marked cytosolic acidification, which was in both cell types blunted by O-methyl-glucose (20 mmol/L) and completely abolished by 100 μmol/L phloretin and 1 mmol/L p-chloromercuribenzene-sulphonic acid (p-CMBS) and in LacZ cells only by glucose (20 mmol/L). The functional characterization points to the involvement of a lactic acid transporter from the monocarboxylate transporter (MCT) family, particularly MCT1. Reverse transcription-polymerase chain reaction (RT-PCR) indeed disclosed the expression of MCT1 and MCT2 in both GLUT1 and LacZ cells. Conclusion. Overexpression of GLUT1 leads to cytosolic alkalinization of mesangial cells depending on functional Na+/H+ exchanger but not on Na+ independent H+ transport.

Original languageEnglish
Pages (from-to)1338-1347
Number of pages10
JournalKidney International
Volume64
Issue number4
DOIs
Publication statusPublished - 1 Oct 2003

Keywords

  • Acidosis
  • Glycolysis
  • H ATPase
  • LacZ
  • MCT
  • NHE

ASJC Scopus subject areas

  • Nephrology

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    Lang, K. S., Mueller, M. M., Tanneur, V., Wallisch, S., Fedorenko, O., Palmada, M., Lang, F., Bröer, S., Heilig, C. W., Schleicher, E., & Weigert, C. (2003). Regulation of cytosolic pH and lactic acid release in mesangial cells overexpressing GLUT1. Kidney International, 64(4), 1338-1347. https://doi.org/10.1046/j.1523-1755.2003.00213.x