Research ExplorerPublicationsReduction of proteinuria through podocyte alkalinization

Reduction of proteinuria through podocyte alkalinization

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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: J BIOL CHEM, Vol. 289, No. 25, 20.06.2014, p. 17454-67.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

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', J BIOL CHEM, vol. 289, no. 25, pp. 17454-67. https://doi.org/10.1074/jbc.M114.568998

APA

Altintas, M. M., Moriwaki, K., Wei, C., Möller, C. C., Flesche, J., Li, J., Yaddanapudi, S., Faridi, M. H., Gödel, M., Huber, T. B., Preston, R. A., Jiang, J. X., Kerjaschki, D., Sever, S., & Reiser, J. (2014). Reduction of proteinuria through podocyte alkalinization. J BIOL CHEM, 289(25), 17454-67. https://doi.org/10.1074/jbc.M114.568998

Vancouver

Altintas MM, Moriwaki K, Wei C, Möller CC, Flesche J, Li J et al. Reduction of proteinuria through podocyte alkalinization. J BIOL CHEM. 2014 Jun 20;289(25):17454-67. https://doi.org/10.1074/jbc.M114.568998

Bibtex

@article{a6b404e5ed8c47559d93fb5c0336ec0f,
title = "Reduction of proteinuria through podocyte alkalinization",
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.",
keywords = "Animals, Biological Transport, Active, Cells, Cultured, Cytoskeleton, Hydrogen-Ion Concentration, Mice, Mice, Knockout, Podocytes, Proteinuria, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't",
author = "Altintas, {Mehmet M} and Kumiko Moriwaki and Changli Wei and M{\"o}ller, {Clemens C} and Jan Flesche and Jing Li and Suma Yaddanapudi and Faridi, {Mohd Hafeez} and Markus G{\"o}del and Huber, {Tobias B} and Preston, {Richard A} and Jiang, {Jean X} and Dontscho Kerjaschki and Sanja Sever and Jochen Reiser",
note = "{\textcopyright} 2014 by The American Society for Biochemistry and Molecular Biology, Inc.",
year = "2014",
month = jun,
day = "20",
doi = "10.1074/jbc.M114.568998",
language = "English",
volume = "289",
pages = "17454--67",
journal = "J BIOL CHEM",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "25",

}

RIS

TY - JOUR

T1 - Reduction of proteinuria through podocyte alkalinization

AU - Altintas, Mehmet M

AU - Moriwaki, Kumiko

AU - Wei, Changli

AU - Möller, Clemens C

AU - Flesche, Jan

AU - Li, Jing

AU - Yaddanapudi, Suma

AU - Faridi, Mohd Hafeez

AU - Gödel, Markus

AU - Huber, Tobias B

AU - Preston, Richard A

AU - Jiang, Jean X

AU - Kerjaschki, Dontscho

AU - Sever, Sanja

AU - Reiser, Jochen

N1 - © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

PY - 2014/6/20

Y1 - 2014/6/20

N2 - 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.

AB - 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.

KW - Animals

KW - Biological Transport, Active

KW - Cells, Cultured

KW - Cytoskeleton

KW - Hydrogen-Ion Concentration

KW - Mice

KW - Mice, Knockout

KW - Podocytes

KW - Proteinuria

KW - Journal Article

KW - Research Support, N.I.H., Extramural

KW - Research Support, Non-U.S. Gov't

U2 - 10.1074/jbc.M114.568998

DO - 10.1074/jbc.M114.568998

M3 - SCORING: Journal article

C2 - 24817115

VL - 289

SP - 17454

EP - 17467

JO - J BIOL CHEM

JF - J BIOL CHEM

SN - 0021-9258

IS - 25

ER -