Detection and identification of a protein-bound imidazolone resulting from the reaction of arginine residues and methylglyoxal

Henle, Thomas; Walter, Axel W.; Haeßner, R.; Klostermeyer, Henning

doi:10.1007/bf01192954

Cited by 107 publications

(69 citation statements)

References 17 publications

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“…13) Addi- tionally, MG-H1 [14][15][16] serves as an index of injury to glyceraldehyde and methylglyoxal-related enzymes in glycolysis. Since GLAP is not formed from MGO, GLAP might serves as a specific marker of reduced activity of a glyceraldehyde-related enzyme (such as GAPDH) in metabolic diseases such as diabetic complications.…”

Section: Resultsmentioning

confidence: 99%

Detection and Determination of Glyceraldehyde-Derived Pyridinium-Type Advanced Glycation End Product in Streptozotocin-Induced Diabetic Rats

Usui

Shimohira

Watanabe

et al. 2007

Bioscience, Biotechnology, and Biochemistry

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Section: Resultsmentioning

confidence: 99%

Detection and Determination of Glyceraldehyde-Derived Pyridinium-Type Advanced Glycation End Product in Streptozotocin-Induced Diabetic Rats

Usui

Shimohira

Watanabe

et al. 2007

Bioscience, Biotechnology, and Biochemistry

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“…residues, an advanced glycation end product (AGE) (17,18), with loss of associated side chain positive charge (19) (Fig. 1B).…”

Section: N␦-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (Mg-h1)mentioning

confidence: 99%

Increased Dicarbonyl Metabolism in Endothelial Cells in Hyperglycemia Induces Anoikis and Impairs Angiogenesis by RGD and GFOGER Motif Modification

Dobler

Ahmed²,

Song³

et al. 2006

Diabetes

246

224

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Chronic vascular disease in diabetes isC hronic vascular disease is the major cause of morbidity and mortality in diabetes (1). This is associated with dysfunction of endothelial cells in hyperglycemia (2) and damage to the endothelium; the latter is indicated in vivo by increased detachment and premature death of endothelial cells by apoptosis (including anoikis) (3,4). A cellular marker of damage to the endothelium, increased number of circulating endothelial cells, in diabetes was not linked directly to glycemic control (HbA 1c [A1C]) (5). Extracellular matrix (ECM) interactions with endothelial cells maintain cell survival (6) and support angiogenesis driven by vascular endothelial-derived growth factor and other angiogenic factors (7). Early stages of microangiopathy and wound healing are characterized by development of acellular capillaries and decreased angiogenesis with consequent ischemia (8). A metabolic link to ECM disengagement of endothelial cells and impaired angiogenesis has not been identified.Most cell adhesion and signaling occur via integrins, which mediate a variety of cell-cell and cell-matrix interactions. The ␣ 1 ␤ 1 and ␣ 2 ␤ 1 integrins recognize the GFOGER sequence found in collagens (9,10) (Fig. 1A). Several integrins recognize the RGD sequence within ECM proteins (6,11) where the RGD moiety binds astride the integrin ␣-and ␤-subunits with the Arg residue making electrostatic interaction with one or two Asp residues of the ␣-subunit (12,13).Methylglyoxal is a potent arginine-directed glycating agent formed mainly by the degradation of triosephosphates (14,15) with increased flux of formation in hyperglycemia associated with diabetes (16). It reacts with arginine residues to form a hydroimidazolone derivative, N␦-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1)residues, an advanced glycation end product (AGE) (17,18), with loss of associated side chain positive charge (19) (Fig. 1B). MG-H1 residues are a major type of protein damage by glycation in diabetes, occurring on both cellular and extracellular proteins (20,21). Increased concentration of MG-H1 residues in plasma protein of diabetic patients was not linked directly to A1C (22), probably because methylglyoxal formation is increased in both fasting and postprandial hyperglycemia (16,23) and influenced by factors other than hyperglycemia (low glyceraldehyde-3-phosphate dehydrogenase activity [24]). MG-H1 residue formation occurred at susceptible hotspot sites in proteins with loss of functional activity (19). The surface sheath network of type IV collagen in blood vessels (25) binds integrins of vascular endothelial cells, anchoring and sustaining the vascular endothelium by interaction with integrins at GFOGER and RGD sites of the triple helical domain (9,26). These integrin binding sites are potential targets for methylglyoxal modification.We report here that modification by methylglyoxal of GFOGER and RGD sites in type IV collagen in hyperglycemia impairs ECM attachment, viability, and angiogenic activity of endothelial ce...

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“…Skovsted et al (36) have also described another imidazolium cross-link, termed DOLD, which is formed by reaction of 3-deoxyglucosone with protein, although this compound has not yet been detected in tissue proteins. Dicarbonyl compounds, such as GO, MGO, and 3-deoxyglucosone, are also known to form imidazolones and dehydroimidazolones on reaction with arginine residues in proteins (19,22,23); however, the relative reactivity of Lys and Arg residues with dicarbonyl compounds has not been rigorously evaluated, in part because of the lack of appropriately sensitive and specific analytical methods for (dehydro)imidazolones.…”

Section: Discussionmentioning

confidence: 99%

“…Besides unidentified brown and fluorescent products, the reaction of GO and MGO with lysine and arginine residues in protein yields well characterized compounds, such as the N-(carboxyalkyl)lysines, N ⑀ -(carboxymethyl)lysine (CML) (20) and N ⑀ -[1-(1-carboxy)ethyl]lysine (CEL) (21), and imidazolones and dehydroimidazolones (19,22,23). Imidazolones have been detected in tissue proteins only by immunological methods, whereas CML and CEL have been measured by gas chromatography/ mass spectometry (GC/MS) and increase in skin collagen and lens protein with age (21, 24 -26).…”

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confidence: 99%

Role of the Maillard Reaction in Aging of Tissue Proteins

Frye

Degenhardt

Thorpe

et al. 1998

Journal of Biological Chemistry

325

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Dicarbonyl compounds such as glyoxal and methylglyoxal are reactive dicarbonyl intermediates in the nonenzymatic browning and cross-linking of proteins during the Maillard reaction. We describe here the quantification of glyoxal and methylglyoxal-derived imidazolium cross-links in tissue proteins. The imidazolium salt cross-links, glyoxal-lysine dimer (GOLD) and methylglyoxal-lysine dimer (MOLD), were measured by liquid chromatography/mass spectrometry and were present in lens protein at concentrations of 0.02-0.2 and 0.1-0.8 mmol/mol of lysine, respectively. The lens concentrations of GOLD and MOLD correlated significantly with one another and also increased with lens age. GOLD and MOLD were present at significantly higher concentrations than the fluorescent cross-links pentosidine and dityrosine, identifying them as major Maillard reaction cross-links in lens proteins. Like the N-carboxy-alkyllysines N ⑀ -(carboxymethyl)lysine and N ⑀ -(carboxyethyl)lysine, these cross-links were also detected at lower concentrations in human skin collagen and increased with age in collagen. The presence of GOLD and MOLD in tissue proteins implicates methylglyoxal and glyoxal, either free or protein-bound, as important precursors of protein cross-links formed during Maillard reactions in vivo during aging and in disease.The Maillard reaction is a complex series of reactions between reducing sugars and amino groups on proteins, which lead to browning, fluorescence, and cross-linking of protein (1, 2). Advanced glycation end products, formed during later stages of the Maillard reaction, accumulate in long lived tissue proteins, such as tissue collagens and lens crystallins, and may contribute to the development of complications in aging, diabetes, and atherosclerosis (3, 4). Glyoxal (GO), 1 methylglyoxal (MGO), and deoxyglucosones belong to a series of dicarbonyl compounds, identified as intermediates in the Maillard reaction. GO is formed on autoxidation of glucose under physiological conditions (5) and also as a product of lipid peroxidation (6). MGO is formed nonenzymatically by spontaneous decomposition of triose phosphate intermediates in glycolysis (7) and by amine-catalyzed sugar fragmentation reactions (8, 9). It is also a product of metabolism of acetone (10) and threonine (11). Both GO and MGO are detoxified by the glutathione-dependent glyoxalase pathway, yielding hydroxyacetic acid and D-lactate, respectively (12-14). MGO can also be detoxified by the NADPHdependent enzyme aldose reductase, yielding 1,2-propanediol (15). The concentration of MGO is elevated in the blood of diabetic patients in vivo (16,17), and the metabolites of MGO detoxification, acetol and 1,2-propanediol, are also increased in blood during diabetic ketoacidosis (10).GO and MGO are reactive toward amino, guanidino, and sulfhydryl functional groups in protein (18,19), leading to browning, denaturation, and cross-linking of proteins. Besides unidentified brown and fluorescent products, the reaction of GO and MGO with lysine and arginine residues in...

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Detection and identification of a protein-bound imidazolone resulting from the reaction of arginine residues and methylglyoxal

Cited by 107 publications

References 17 publications

Detection and Determination of Glyceraldehyde-Derived Pyridinium-Type Advanced Glycation End Product in Streptozotocin-Induced Diabetic Rats

Detection and Determination of Glyceraldehyde-Derived Pyridinium-Type Advanced Glycation End Product in Streptozotocin-Induced Diabetic Rats

Increased Dicarbonyl Metabolism in Endothelial Cells in Hyperglycemia Induces Anoikis and Impairs Angiogenesis by RGD and GFOGER Motif Modification

Role of the Maillard Reaction in Aging of Tissue Proteins

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