Reduction of proteinuria through podocyte alkalinization

Mehmet M. Altintas, Kumiko Moriwaki, Changli Wei, Clemens C. Möller, Jan Flesche, Jing Li, Suma Yaddanapudi, Mohd Hafeez Faridi, Markus Gödel, Tobias B. Huber, Richard A Preston, Jean X. Jiang, Dontscho Kerjaschki, Sanja Sever, Jochen Reiser

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Podocytes are highly differentiated cells and critical elements for the filtration barrier of the kidney. Loss of their foot process (FP) architecture (FP effacement) results in urinary protein loss. Here we show a novel role for the neutral amino acid glutamine in structural and functional regulation of the kidney filtration barrier. Metabolic flux analysis of cultured podocytes using genetic, toxic, and immunologic injury models identified increased glutamine utilization pathways. We show that glutamine uptake is increased in diseased podocytes to couple nutrient support to increased demand during the disease state of FP effacement. This feature can be utilized to transport increased amounts of glutamine into damaged podocytes. The availability of glutamine determines the regulation of podocyte intracellular pH (pHi). Podocyte alkalinization reduces cytosolic cathepsin L protease activity and protects the podocyte cytoskeleton. Podocyte glutamine supplementation reduces proteinuria in LPS-treated mice, whereas acidification increases glomerular injury. In summary, our data provide a metabolic opportunity to combat urinary protein loss through modulation of podocyte amino acid utilization and pHi.

Original languageEnglish
Pages (from-to)17454-17467
Number of pages14
JournalJournal of Biological Chemistry
Volume289
Issue number25
DOIs
StatePublished - Jun 20 2014

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Podocytes
Glutamine
Proteinuria
Neutral Amino Acids
Cathepsin L
Acidification
Foot
Poisons
Immunological Models
Metabolic Flux Analysis
Foot Diseases
Nutrients
Kidney
Proteins
Peptide Hydrolases
Wounds and Injuries
Modulation
Availability
Fluxes
Cytoskeleton

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Altintas, M. M., Moriwaki, K., Wei, C., Möller, C. C., Flesche, J., Li, J., ... Reiser, J. (2014). Reduction of proteinuria through podocyte alkalinization. Journal of Biological Chemistry, 289(25), 17454-17467. https://doi.org/10.1074/jbc.M114.568998

Reduction of proteinuria through podocyte alkalinization. / Altintas, Mehmet M.; Moriwaki, Kumiko; Wei, Changli; Möller, Clemens C.; Flesche, Jan; Li, Jing; Yaddanapudi, Suma; Faridi, Mohd Hafeez; Gödel, Markus; Huber, Tobias B.; Preston, Richard A; Jiang, Jean X.; Kerjaschki, Dontscho; Sever, Sanja; Reiser, Jochen.

In: Journal of Biological Chemistry, Vol. 289, No. 25, 20.06.2014, p. 17454-17467.

Research output: Contribution to journalArticle

Altintas, MM, Moriwaki, K, Wei, C, Möller, CC, Flesche, J, Li, J, Yaddanapudi, S, Faridi, MH, Gödel, M, Huber, TB, Preston, RA, Jiang, JX, Kerjaschki, D, Sever, S & Reiser, J 2014, 'Reduction of proteinuria through podocyte alkalinization', Journal of Biological Chemistry, vol. 289, no. 25, pp. 17454-17467. https://doi.org/10.1074/jbc.M114.568998
Altintas MM, Moriwaki K, Wei C, Möller CC, Flesche J, Li J et al. Reduction of proteinuria through podocyte alkalinization. Journal of Biological Chemistry. 2014 Jun 20;289(25):17454-17467. https://doi.org/10.1074/jbc.M114.568998
Altintas, Mehmet M. ; Moriwaki, Kumiko ; Wei, Changli ; Möller, Clemens C. ; Flesche, Jan ; Li, Jing ; Yaddanapudi, Suma ; Faridi, Mohd Hafeez ; Gödel, Markus ; Huber, Tobias B. ; Preston, Richard A ; Jiang, Jean X. ; Kerjaschki, Dontscho ; Sever, Sanja ; Reiser, Jochen. / Reduction of proteinuria through podocyte alkalinization. In: Journal of Biological Chemistry. 2014 ; Vol. 289, No. 25. pp. 17454-17467.
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