Chronic increase of urea leads to carbamylated proteins accumulation in tissues in a mouse model of CKD.

Carbamylation is a general process involved in protein molecular ageing due to the nonenzymatic binding of isocyanic acid, mainly generated by urea dissociation, to free amino groups. In vitro experiments and clinical studies have suggested the potential involvement of carbamylated proteins (CPs) in...

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Autores principales:	Christine Pietrement, Laëtitia Gorisse, Stéphane Jaisson, Philippe Gillery
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9222d320f34d4b7c831552cff51fa7bf
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spelling	oai:doaj.org-article:9222d320f34d4b7c831552cff51fa7bf2021-11-18T08:43:26ZChronic increase of urea leads to carbamylated proteins accumulation in tissues in a mouse model of CKD.1932-620310.1371/journal.pone.0082506https://doaj.org/article/9222d320f34d4b7c831552cff51fa7bf2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24324801/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Carbamylation is a general process involved in protein molecular ageing due to the nonenzymatic binding of isocyanic acid, mainly generated by urea dissociation, to free amino groups. In vitro experiments and clinical studies have suggested the potential involvement of carbamylated proteins (CPs) in chronic kidney disease (CKD) complications like atherosclerosis, but their metabolic fate in vivo is still unknown. To address this issue, we evaluated protein carbamylation in the plasma and tissues of control and 75% nephrectomised C57BL/6J mice by LC-MS/MS assay of homocitrulline, the major carbamylation-derived product (CDP). A basal level of carbamylation was evidenced under all conditions, showing that carbamylation is a physiological process of protein modification in vivo. CP plasma concentrations increased in nephrectomized vs. control mice over the 20 weeks of the experiment (e.g. 335 ± 43 vs. 167 ± 19 μmol homocitrulline/mol lysine (p<0.001) 20 weeks after nephrectomy). Simultaneously, CP content increased roughly by two-fold in all tissues throughout the experiment. The progressive accumulation of CPs was specifically noted in long-lived extracellular matrix proteins, especially collagen (e.g. 1264 ± 123 vs. 726 ± 99 μmol homocitrulline/mol lysine (p<0.01) in the skin of nephrectomized vs. control mice after 20 weeks of evolution). These results show that chronic increase of urea, as seen in CKD, increases the carbamylation rate of plasma and tissue proteins. These results may be considered in the perspective of the deleterious effects of CPs demonstrated in vitro and of the correlation evidenced recently between plasma CPs and cardiovascular risk or mortality in CKD patients.Christine PietrementLaëtitia GorisseStéphane JaissonPhilippe GilleryPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 12, p e82506 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Christine Pietrement Laëtitia Gorisse Stéphane Jaisson Philippe Gillery Chronic increase of urea leads to carbamylated proteins accumulation in tissues in a mouse model of CKD.
description	Carbamylation is a general process involved in protein molecular ageing due to the nonenzymatic binding of isocyanic acid, mainly generated by urea dissociation, to free amino groups. In vitro experiments and clinical studies have suggested the potential involvement of carbamylated proteins (CPs) in chronic kidney disease (CKD) complications like atherosclerosis, but their metabolic fate in vivo is still unknown. To address this issue, we evaluated protein carbamylation in the plasma and tissues of control and 75% nephrectomised C57BL/6J mice by LC-MS/MS assay of homocitrulline, the major carbamylation-derived product (CDP). A basal level of carbamylation was evidenced under all conditions, showing that carbamylation is a physiological process of protein modification in vivo. CP plasma concentrations increased in nephrectomized vs. control mice over the 20 weeks of the experiment (e.g. 335 ± 43 vs. 167 ± 19 μmol homocitrulline/mol lysine (p<0.001) 20 weeks after nephrectomy). Simultaneously, CP content increased roughly by two-fold in all tissues throughout the experiment. The progressive accumulation of CPs was specifically noted in long-lived extracellular matrix proteins, especially collagen (e.g. 1264 ± 123 vs. 726 ± 99 μmol homocitrulline/mol lysine (p<0.01) in the skin of nephrectomized vs. control mice after 20 weeks of evolution). These results show that chronic increase of urea, as seen in CKD, increases the carbamylation rate of plasma and tissue proteins. These results may be considered in the perspective of the deleterious effects of CPs demonstrated in vitro and of the correlation evidenced recently between plasma CPs and cardiovascular risk or mortality in CKD patients.
format	article
author	Christine Pietrement Laëtitia Gorisse Stéphane Jaisson Philippe Gillery
author_facet	Christine Pietrement Laëtitia Gorisse Stéphane Jaisson Philippe Gillery
author_sort	Christine Pietrement
title	Chronic increase of urea leads to carbamylated proteins accumulation in tissues in a mouse model of CKD.
title_short	Chronic increase of urea leads to carbamylated proteins accumulation in tissues in a mouse model of CKD.
title_full	Chronic increase of urea leads to carbamylated proteins accumulation in tissues in a mouse model of CKD.
title_fullStr	Chronic increase of urea leads to carbamylated proteins accumulation in tissues in a mouse model of CKD.
title_full_unstemmed	Chronic increase of urea leads to carbamylated proteins accumulation in tissues in a mouse model of CKD.
title_sort	chronic increase of urea leads to carbamylated proteins accumulation in tissues in a mouse model of ckd.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/9222d320f34d4b7c831552cff51fa7bf
work_keys_str_mv	AT christinepietrement chronicincreaseofurealeadstocarbamylatedproteinsaccumulationintissuesinamousemodelofckd AT laetitiagorisse chronicincreaseofurealeadstocarbamylatedproteinsaccumulationintissuesinamousemodelofckd AT stephanejaisson chronicincreaseofurealeadstocarbamylatedproteinsaccumulationintissuesinamousemodelofckd AT philippegillery chronicincreaseofurealeadstocarbamylatedproteinsaccumulationintissuesinamousemodelofckd
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Chronic increase of urea leads to carbamylated proteins accumulation in tissues in a mouse model of CKD.

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