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Proteomic Analysis of Methylglyoxal Modifications Reveals Susceptibility of Glycolytic Enzymes to Dicarbonyl Stress

Methylglyoxal (MGO) is a highly reactive cellular metabolite that glycates lysine and arginine residues to form post-translational modifications known as advanced glycation end products. Because of their low abundance and low stoichiometry, few studies have reported their occurrence and site-specifi...

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Autores principales: Donnellan, Leigh, Young, Clifford, Simpson, Bradley S., Acland, Mitchell, Dhillon, Varinderpal S., Costabile, Maurizio, Fenech, Michael, Hoffmann, Peter, Deo, Permal
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8998448/
https://www.ncbi.nlm.nih.gov/pubmed/35409048
http://dx.doi.org/10.3390/ijms23073689
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author Donnellan, Leigh
Young, Clifford
Simpson, Bradley S.
Acland, Mitchell
Dhillon, Varinderpal S.
Costabile, Maurizio
Fenech, Michael
Hoffmann, Peter
Deo, Permal
author_facet Donnellan, Leigh
Young, Clifford
Simpson, Bradley S.
Acland, Mitchell
Dhillon, Varinderpal S.
Costabile, Maurizio
Fenech, Michael
Hoffmann, Peter
Deo, Permal
author_sort Donnellan, Leigh
collection PubMed
description Methylglyoxal (MGO) is a highly reactive cellular metabolite that glycates lysine and arginine residues to form post-translational modifications known as advanced glycation end products. Because of their low abundance and low stoichiometry, few studies have reported their occurrence and site-specific locations in proteins. Proteomic analysis of WIL2-NS B lymphoblastoid cells in the absence and presence of exogenous MGO was conducted to investigate the extent of MGO modifications. We found over 500 MGO modified proteins, revealing an over-representation of these modifications on many glycolytic enzymes, as well as ribosomal and spliceosome proteins. Moreover, MGO modifications were observed on the active site residues of glycolytic enzymes that could alter their activity. We similarly observed modification of glycolytic enzymes across several epithelial cell lines and peripheral blood lymphocytes, with modification of fructose bisphosphate aldolase being observed in all samples. These results indicate that glycolytic proteins could be particularly prone to the formation of MGO adducts.
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spelling pubmed-89984482022-04-12 Proteomic Analysis of Methylglyoxal Modifications Reveals Susceptibility of Glycolytic Enzymes to Dicarbonyl Stress Donnellan, Leigh Young, Clifford Simpson, Bradley S. Acland, Mitchell Dhillon, Varinderpal S. Costabile, Maurizio Fenech, Michael Hoffmann, Peter Deo, Permal Int J Mol Sci Article Methylglyoxal (MGO) is a highly reactive cellular metabolite that glycates lysine and arginine residues to form post-translational modifications known as advanced glycation end products. Because of their low abundance and low stoichiometry, few studies have reported their occurrence and site-specific locations in proteins. Proteomic analysis of WIL2-NS B lymphoblastoid cells in the absence and presence of exogenous MGO was conducted to investigate the extent of MGO modifications. We found over 500 MGO modified proteins, revealing an over-representation of these modifications on many glycolytic enzymes, as well as ribosomal and spliceosome proteins. Moreover, MGO modifications were observed on the active site residues of glycolytic enzymes that could alter their activity. We similarly observed modification of glycolytic enzymes across several epithelial cell lines and peripheral blood lymphocytes, with modification of fructose bisphosphate aldolase being observed in all samples. These results indicate that glycolytic proteins could be particularly prone to the formation of MGO adducts. MDPI 2022-03-28 /pmc/articles/PMC8998448/ /pubmed/35409048 http://dx.doi.org/10.3390/ijms23073689 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Donnellan, Leigh
Young, Clifford
Simpson, Bradley S.
Acland, Mitchell
Dhillon, Varinderpal S.
Costabile, Maurizio
Fenech, Michael
Hoffmann, Peter
Deo, Permal
Proteomic Analysis of Methylglyoxal Modifications Reveals Susceptibility of Glycolytic Enzymes to Dicarbonyl Stress
title Proteomic Analysis of Methylglyoxal Modifications Reveals Susceptibility of Glycolytic Enzymes to Dicarbonyl Stress
title_full Proteomic Analysis of Methylglyoxal Modifications Reveals Susceptibility of Glycolytic Enzymes to Dicarbonyl Stress
title_fullStr Proteomic Analysis of Methylglyoxal Modifications Reveals Susceptibility of Glycolytic Enzymes to Dicarbonyl Stress
title_full_unstemmed Proteomic Analysis of Methylglyoxal Modifications Reveals Susceptibility of Glycolytic Enzymes to Dicarbonyl Stress
title_short Proteomic Analysis of Methylglyoxal Modifications Reveals Susceptibility of Glycolytic Enzymes to Dicarbonyl Stress
title_sort proteomic analysis of methylglyoxal modifications reveals susceptibility of glycolytic enzymes to dicarbonyl stress
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8998448/
https://www.ncbi.nlm.nih.gov/pubmed/35409048
http://dx.doi.org/10.3390/ijms23073689
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