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Increased plasma phenylacetic acid in patients with end-stage renal failure inhibits iNOS expression

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Increased plasma phenylacetic acid in patients with end-stage renal failure inhibits iNOS expression. / Jankowski, J; van der Giet, M; Jankowski, V; Schmidt, S; Hemeier, M; Mahn, B; Giebing, G; Tolle, M; Luftmann, H; Schluter, H; Zidek, W; Tepel, M.

In: J CLIN INVEST, Vol. 112, No. 2, 07.2003, p. 256-64.

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

Harvard

Jankowski, J, van der Giet, M, Jankowski, V, Schmidt, S, Hemeier, M, Mahn, B, Giebing, G, Tolle, M, Luftmann, H, Schluter, H, Zidek, W & Tepel, M 2003, 'Increased plasma phenylacetic acid in patients with end-stage renal failure inhibits iNOS expression', J CLIN INVEST, vol. 112, no. 2, pp. 256-64. https://doi.org/10.1172/JCI15524

APA

Jankowski, J., van der Giet, M., Jankowski, V., Schmidt, S., Hemeier, M., Mahn, B., Giebing, G., Tolle, M., Luftmann, H., Schluter, H., Zidek, W., & Tepel, M. (2003). Increased plasma phenylacetic acid in patients with end-stage renal failure inhibits iNOS expression. J CLIN INVEST, 112(2), 256-64. https://doi.org/10.1172/JCI15524

Vancouver

Jankowski J, van der Giet M, Jankowski V, Schmidt S, Hemeier M, Mahn B et al. Increased plasma phenylacetic acid in patients with end-stage renal failure inhibits iNOS expression. J CLIN INVEST. 2003 Jul;112(2):256-64. https://doi.org/10.1172/JCI15524

Bibtex

@article{834a65760017442c9b4f508ec5febd59,
title = "Increased plasma phenylacetic acid in patients with end-stage renal failure inhibits iNOS expression",
abstract = "NO prevents atherogenesis and inflammation in vessel walls by inhibition of cell proliferation and cytokine-induced endothelial expression of adhesion molecules and proinflammatory cytokines. Reduced NO production due to inhibition of either eNOS or iNOS may therefore reinforce atherosclerosis. Patients with end-stage renal failure show markedly increased mortality due to atherosclerosis. In the present study we tested the hypothesis that uremic toxins are responsible for reduced iNOS expression. LPS-induced iNOS expression in mononuclear leukocytes was studied using real-time PCR. The iNOS expression was blocked by addition of plasma from patients with end-stage renal failure, whereas plasma from healthy controls had no effect. Hemofiltrate obtained from patients with end-stage renal failure was fractionated by chromatographic methods. The chromatographic procedures revealed a homogenous fraction that inhibits iNOS expression. Using gas chromatography/mass spectrometry, this inhibitor was identified as phenylacetic acid. Authentic phenylacetic acid inhibited iNOS expression in a dose-dependent manner. In healthy control subjects, plasma concentrations were below the detection level, whereas patients with end-stage renal failure had a phenylacetic acid concentration of 3.49 +/- 0.33 mmol/l (n = 41). It is concluded that accumulation of phenylacetic acid in patients with end-stage renal failure inhibits iNOS expression. That mechanism may contribute to increased atherosclerosis and cardiovascular morbidity in patients with end-stage renal failure.",
keywords = "Adult, Aged, Animals, Blotting, Western, Cell Line, Cell Survival, Cells, Cultured, Dose-Response Relationship, Drug, Electrophoresis, Polyacrylamide Gel, Female, Gas Chromatography-Mass Spectrometry, Humans, Kidney Failure, Chronic, Leukocytes, Mononuclear, Macrophages, Magnetic Resonance Spectroscopy, Male, Mass Spectrometry, Mice, Middle Aged, Nitric Oxide, Nitric Oxide Synthase, Nitric Oxide Synthase Type II, Nitrites, Phenylacetates, Reverse Transcriptase Polymerase Chain Reaction, Journal Article",
author = "J Jankowski and {van der Giet}, M and V Jankowski and S Schmidt and M Hemeier and B Mahn and G Giebing and M Tolle and H Luftmann and H Schluter and W Zidek and M Tepel",
year = "2003",
month = jul,
doi = "10.1172/JCI15524",
language = "English",
volume = "112",
pages = "256--64",
journal = "J CLIN INVEST",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "2",

}

RIS

TY - JOUR

T1 - Increased plasma phenylacetic acid in patients with end-stage renal failure inhibits iNOS expression

AU - Jankowski, J

AU - van der Giet, M

AU - Jankowski, V

AU - Schmidt, S

AU - Hemeier, M

AU - Mahn, B

AU - Giebing, G

AU - Tolle, M

AU - Luftmann, H

AU - Schluter, H

AU - Zidek, W

AU - Tepel, M

PY - 2003/7

Y1 - 2003/7

N2 - NO prevents atherogenesis and inflammation in vessel walls by inhibition of cell proliferation and cytokine-induced endothelial expression of adhesion molecules and proinflammatory cytokines. Reduced NO production due to inhibition of either eNOS or iNOS may therefore reinforce atherosclerosis. Patients with end-stage renal failure show markedly increased mortality due to atherosclerosis. In the present study we tested the hypothesis that uremic toxins are responsible for reduced iNOS expression. LPS-induced iNOS expression in mononuclear leukocytes was studied using real-time PCR. The iNOS expression was blocked by addition of plasma from patients with end-stage renal failure, whereas plasma from healthy controls had no effect. Hemofiltrate obtained from patients with end-stage renal failure was fractionated by chromatographic methods. The chromatographic procedures revealed a homogenous fraction that inhibits iNOS expression. Using gas chromatography/mass spectrometry, this inhibitor was identified as phenylacetic acid. Authentic phenylacetic acid inhibited iNOS expression in a dose-dependent manner. In healthy control subjects, plasma concentrations were below the detection level, whereas patients with end-stage renal failure had a phenylacetic acid concentration of 3.49 +/- 0.33 mmol/l (n = 41). It is concluded that accumulation of phenylacetic acid in patients with end-stage renal failure inhibits iNOS expression. That mechanism may contribute to increased atherosclerosis and cardiovascular morbidity in patients with end-stage renal failure.

AB - NO prevents atherogenesis and inflammation in vessel walls by inhibition of cell proliferation and cytokine-induced endothelial expression of adhesion molecules and proinflammatory cytokines. Reduced NO production due to inhibition of either eNOS or iNOS may therefore reinforce atherosclerosis. Patients with end-stage renal failure show markedly increased mortality due to atherosclerosis. In the present study we tested the hypothesis that uremic toxins are responsible for reduced iNOS expression. LPS-induced iNOS expression in mononuclear leukocytes was studied using real-time PCR. The iNOS expression was blocked by addition of plasma from patients with end-stage renal failure, whereas plasma from healthy controls had no effect. Hemofiltrate obtained from patients with end-stage renal failure was fractionated by chromatographic methods. The chromatographic procedures revealed a homogenous fraction that inhibits iNOS expression. Using gas chromatography/mass spectrometry, this inhibitor was identified as phenylacetic acid. Authentic phenylacetic acid inhibited iNOS expression in a dose-dependent manner. In healthy control subjects, plasma concentrations were below the detection level, whereas patients with end-stage renal failure had a phenylacetic acid concentration of 3.49 +/- 0.33 mmol/l (n = 41). It is concluded that accumulation of phenylacetic acid in patients with end-stage renal failure inhibits iNOS expression. That mechanism may contribute to increased atherosclerosis and cardiovascular morbidity in patients with end-stage renal failure.

KW - Adult

KW - Aged

KW - Animals

KW - Blotting, Western

KW - Cell Line

KW - Cell Survival

KW - Cells, Cultured

KW - Dose-Response Relationship, Drug

KW - Electrophoresis, Polyacrylamide Gel

KW - Female

KW - Gas Chromatography-Mass Spectrometry

KW - Humans

KW - Kidney Failure, Chronic

KW - Leukocytes, Mononuclear

KW - Macrophages

KW - Magnetic Resonance Spectroscopy

KW - Male

KW - Mass Spectrometry

KW - Mice

KW - Middle Aged

KW - Nitric Oxide

KW - Nitric Oxide Synthase

KW - Nitric Oxide Synthase Type II

KW - Nitrites

KW - Phenylacetates

KW - Reverse Transcriptase Polymerase Chain Reaction

KW - Journal Article

U2 - 10.1172/JCI15524

DO - 10.1172/JCI15524

M3 - SCORING: Journal article

C2 - 12865413

VL - 112

SP - 256

EP - 264

JO - J CLIN INVEST

JF - J CLIN INVEST

SN - 0021-9738

IS - 2

ER -