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1.
Biosci Biotechnol Biochem ; 82(9): 1508-1514, 2018 Sep.
Article in English | MEDLINE | ID: mdl-29804507

ABSTRACT

Advanced glycation end-products (AGEs) elicit inflammatory responses via the receptor for AGEs (RAGE) and participate in the pathogenesis of diabetic complications. An earlier study showed that 3-hydroxypyridinium (3-HP), a common moiety of toxic AGEs such as glyceraldehyde-derived pyridinium (GLAP) and GA-pyridine, is essential for the interaction with RAGE. However, the physiological significance of 3-HP recognition by RAGE remains unclear. We hypothesized that pyridinoline (Pyr), a collagen crosslink containing the 3-HP moiety, could have agonist activity with RAGE. To test this hypothesis, we purified Pyr from bovine achilles tendons and examined its cytotoxicity to rat neuronal PC12 cells. Pyr elicited toxicity to PC12 cells in a concentration-dependent manner, and this effect was attenuated in the presence of either the anti-RAGE antibody or the soluble form of RAGE. Moreover, surface plasmon resonance-based analysis showed specific binding of Pyr to RAGE. These data indicate that Pyr is an intrinsic ligand for RAGE. ABBREVIATIONS: AGEs: advanced glycation end-products; RAGE: receptor for advanced glycation end-products; DAMPs: damage-associated molecular patterns; PRR: pattern recognition receptor; TLR: toll-like receptor; GLAP: glyceraldehyde-derived pyridinium; 3-HP: 3-hydroxypyridinium; Pyr: pyridinoline; HFBA: heptafluorobutyric acid; GST: glutathione S-transferase; SPR: surface plasmon resonance; ECM: extracellular matrix; EMT: epithelial to mesenchymal transition.


Subject(s)
Amino Acids/metabolism , Collagen/metabolism , Cross-Linking Reagents/metabolism , Receptor for Advanced Glycation End Products/metabolism , Amino Acids/chemistry , Animals , Cattle , Ligands , Maillard Reaction , PC12 Cells , Rats , Receptor for Advanced Glycation End Products/immunology , Structure-Activity Relationship , Surface Plasmon Resonance , Tendons/metabolism
2.
Biosci Biotechnol Biochem ; 82(2): 312-319, 2018 Feb.
Article in English | MEDLINE | ID: mdl-29316860

ABSTRACT

Advanced glycation end products (AGEs) formed from glyceraldehyde (Gcer) and glycolaldehyde (Gcol) are involved in the pathogenesis of diabetic complications, via interactions with a receptor for AGEs (RAGE). In this study, we aimed to elucidate the RAGE-binding structure in Gcer and Gcol-derived AGEs and identify the minimal moiety recognized by RAGE. Among Gcer and Gcol-derived AGEs, GLAP (glyceraldehyde-derived pyridinium) and GA-pyridine elicited toxicity in PC12 neuronal cells. The toxic effects of GLAP and GA-pyridine were suppressed in the presence of anti-RAGE antibody or the soluble form of RAGE protein. Furthermore, the cytotoxicity test using GLAP analog compounds indicated that the 3-hydroxypyridinium (3-HP) structure is sufficient for RAGE-dependent toxicity. Surface plasmon resonance analysis showed that 3-HP derivatives directly interact with RAGE. These results indicate that GLAP and GA-pyridine are RAGE-binding epitopes, and that 3-HP, a common moiety of GLAP and GA-pyridine, is essential for the interaction with RAGE.


Subject(s)
Cytotoxins/chemistry , Cytotoxins/toxicity , Pyridines/chemistry , Pyridines/toxicity , Receptor for Advanced Glycation End Products/metabolism , Acetaldehyde/analogs & derivatives , Acetaldehyde/metabolism , Animals , Glyceraldehyde/metabolism , Humans , Oxidative Stress/drug effects , PC12 Cells , Rats
3.
Biosci Biotechnol Biochem ; 72(2): 568-71, 2008 Feb.
Article in English | MEDLINE | ID: mdl-18256486

ABSTRACT

Three major glyceraldehyde-related advanced glycation end products (AGEs) were formed from a mixture of N(alpha)-acetyllysine, N(alpha)-acetylarginine, and glyceraldehyde. Two of the compounds were MG-H1 and GLAP, as previously reported, and the other compound was identified as N(alpha)-acetyl-N(delta)-(5-hydroxy-4,6-dimethyl-pyrimidin-2-yl)-ornithine, argpyrimidine (APN). APN is a modification product of arginine residue, but it did not form from glyceraldehyde with arginine residue. The coexistence of lysine residue was necessary to APN formation.


Subject(s)
Glucose/chemistry , Glyceraldehyde/chemistry , Ornithine/analogs & derivatives , Pyrimidines/chemical synthesis , Magnetic Resonance Spectroscopy , Ornithine/chemical synthesis , Spectrometry, Fluorescence , Spectrometry, Mass, Fast Atom Bombardment , Spectrophotometry, Ultraviolet
4.
Ann N Y Acad Sci ; 1126: 53-8, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18079473

ABSTRACT

The formation mechanisms of melanoidins as advanced glycation end products (AGEs) have not been resolved. Blue and red pigments generated in the D-xylose-glycine reaction system are postulated to be intermediate oligomers in the generation of melanoidins. A novel blue pigment, designated blue-M5, was identified as a similar structure to blue-M1 except for the side chain of two dihydroxypropyl groups. Blue pigments were also generated in the D-glucose-glycine and D-xylose-beta-alanine reaction systems as well as in the D-xylose-glycine reaction system. Blue pigments by the Maillard reaction might be formed by the decarboxylation of two molecules of pyrrolopyrrole-2-carbaldehydes (PPA). PPA, composed of a side chain of a dihydroxypropyl group, was identified as a precursor of blue pigments. In fact, blue-M5 was generated by the incubation of PPA alone. Blue pigments, which involved pyrrolopyrrole structures, were readily changed to brown polymers. Glyceraldehyde-derived pyridinium (GLAP) compound, a glyceraldehyde-derived fluorescent AGE, and lysyl-pyrropyridine, a 3-deoxyglucosone-derived fluorescent AGE, were detected at higher levels in the plasma proteins and the tail tendon collagen of streptozotocin-induced diabetic rats compared to normal rats. GLAP and lysyl-pyrropyridine, therefore, might be related to the progression of diabetic complications.


Subject(s)
Glycation End Products, Advanced/metabolism , Polymers/metabolism , Pyridinium Compounds/metabolism , Animals , Diabetes Mellitus, Experimental/metabolism , Glycation End Products, Advanced/chemistry , Glyceraldehyde/analysis , Glyceraldehyde/metabolism , Magnetic Resonance Spectroscopy , Maillard Reaction , Polymers/chemistry , Pyridinium Compounds/chemistry , Rats
5.
Biosci Biotechnol Biochem ; 71(10): 2465-72, 2007 Oct.
Article in English | MEDLINE | ID: mdl-17928698

ABSTRACT

The alpha-dicarbonyl compounds formed in the degradation of glucose and fructose were analyzed by HPLC using 2,3-diaminonaphthalene as derivatizing reagent, and identified as glucosone (GLUCO), 3-deoxyglucosone (3DG), 3-deoxyxylosone (3DX), tetrosone (TSO), triosone (TRIO), 3-deoxytetrosone (3DT), glyoxal (GO), and methylglyoxal (MGO). The results suggest that alpha-dicarbonyl compounds were formed from glucose via non-oxidative 3-deoxyglucosone formation and oxidative glucosone formation in glucose degradation. In addition, TRIO, GO, and MGO were also formed from glyceraldehyde as intermediate. The alpha-dicarbonyl compounds might be formed from glucose via these pathways in diabetes.


Subject(s)
Deoxyglucose/analogs & derivatives , Fructose/metabolism , Glucose/metabolism , Glycation End Products, Advanced/metabolism , Glyoxal/metabolism , Ketoses/metabolism , Chromatography, High Pressure Liquid , Deoxyglucose/chemistry , Deoxyglucose/metabolism , Glycation End Products, Advanced/analysis , Glycation End Products, Advanced/chemistry , Glyoxal/chemistry , Ketoses/chemistry , Maillard Reaction , Models, Chemical , Molecular Structure
6.
Biosci Biotechnol Biochem ; 71(9): 2162-8, 2007 Sep.
Article in English | MEDLINE | ID: mdl-17827699

ABSTRACT

Glyceraldehyde (GLA) was determined in glucose degradation and glycation. GLA was detected as a decahydroacridine-1,8-dione derivative on reversed phase HPLC using cyclohexane-1,3-dione derivatizing reagent. The glucose-derived GLA level was higher than the glycation-derived GLA level, because GLA was converted to intermediates and advanced glycation end products (AGE) in glycation. GLA was also generated from 3-deoxyglucosone and glucosone as intermediates of glucose degradation and glycation. This study suggests that glyceraldehyde is generated by hyperglycemia in diabetes, and that it is also formed in medicines such as peritoneal dialysis solution.


Subject(s)
Glucose/chemistry , Glyceraldehyde/chemistry , Chromatography, High Pressure Liquid , Glycosylation , Ketoses/chemistry , Molecular Structure
7.
Biosci Biotechnol Biochem ; 71(2): 442-8, 2007 Feb.
Article in English | MEDLINE | ID: mdl-17284838

ABSTRACT

GLAP, glyceraldehyde-derived pyridinium-type advanced glycation end product (AGE), formed by glyceraldehyde-related glycation, was identified in the plasma protein and the tail tendon collagen of streptozotocin (STZ)-induced diabetic rats. It was detected in the plasma protein and the collagen in diabetic rats by LC-MS and LC-MS/MS analysis, but was not detected in normal rats. In addition, GLAP was formed from glyceraldehyde-3-phosphate (GA3P) with lysine as well as glyceraldehyde (GLA) with lysine in vitro. Accordingly, it is suggested that an increase in the GLAP level reflects an increase in the GLA level and the GA3P level. GLAP might be a biomarker for reduced activity of the glyceraldehyde-related enzymes in the metabolic diseases such as diabetic complications.


Subject(s)
Diabetes Mellitus, Experimental/blood , Glycation End Products, Advanced/blood , Glyceraldehyde/blood , Pyridinium Compounds/blood , Animals , Collagen/analysis , Glyceraldehyde 3-Phosphate/analysis , Hydrolysis , Indicators and Reagents , Male , Proteins/chemistry , Rats , Rats, Sprague-Dawley , Serum Albumin, Bovine/analysis , Spectrometry, Fluorescence , Tail/chemistry , Tendons/chemistry
8.
Mol Nutr Food Res ; 50(12): 1171-9, 2006 Dec.
Article in English | MEDLINE | ID: mdl-17131457

ABSTRACT

Various pigments were formed in the D-xylose-glycine reaction system. Blue pigments (Blue-M1 and Blue-M2) and red pigments (Red-M1 and Red-M2) were generated in the Maillard reaction. Blue-M2 is presented to have been generated by the reaction between Blue-M1, which involved two pyrrolopyrrole structures as the major blue pigment, and di-D-xyluloseglycine. We identified red pigments as the isomers of addition compounds of D-xyluloseglycine to condensated compound between pyrroropyrrole-2-carbaldehyde and pyrrole-2-carbaldehyde compounds. These pigments have polymerizing activities, suggesting that they are important Maillard reaction intermediates through the formation of melanoidins. Blue-M1 as well as melanoidins effectively suppressed the peroxidation of linoleic acid. The scavenging activity toward Blue-M1 on hydroxyl and DPPH radicals was also as strong as that of melanoidins. Furthermore, Blue-M1 prevents the oxidative cell injury. Therefore, Blue-M1 will be an antioxidant which protects against the oxidative stress in biological systems. Melanoidins induced IFN-gamma mRNA and IL-12 mRNA expressions in spleen cells exposed to allergen and in macrophage-like J774.1 cells, respectively. These findings suggest that melanoidins have suppressive effect on allergic reaction as a novel physiological effect.


Subject(s)
Maillard Reaction , Pigments, Biological/chemistry , Pigments, Biological/pharmacology , Polymers/chemistry , Polymers/pharmacology , Animals , Antioxidants/pharmacology , Butylamines/chemistry , COS Cells , Cell Death/drug effects , Cell Line , Cells, Cultured , Chlorocebus aethiops , Glycerol/analogs & derivatives , Glycerol/chemical synthesis , Glycerol/pharmacology , Glycine/chemistry , Hypersensitivity/prevention & control , Lipid Peroxidation/drug effects , Macrophages/drug effects , Macrophages/immunology , Mice , Pyrroles/chemical synthesis , Pyrroles/pharmacology , Spleen/drug effects , Spleen/immunology , Xylose/chemistry
9.
Biosci Biotechnol Biochem ; 70(6): 1496-8, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16794333

ABSTRACT

We isolated and identified the glyceraldehyde-derived advanced glycation product (AGE) formed from glyceraldehyde and N(alpha)-acetylarginine. A major product was identified as N(alpha)-acetyl-N(delta)-(5-methyl-imidazolin-4-one-2-yl)-ornithine. The compound has been reported as methylglyoxal-derived AGE, MG-H1. This study suggests that MG-H1 is formed through both glyceraldehyde-related and methylglyoxal-related pathways. There is a possibility that MG-H1 becomes an index of injury to glyceraldehyde and methylglyoxal-related enzymes.


Subject(s)
Glycation End Products, Advanced/chemistry , Glycation End Products, Advanced/isolation & purification , Glyceraldehyde/chemistry , Imidazolines/chemistry , Chromatography, High Pressure Liquid , Molecular Structure
10.
Ann N Y Acad Sci ; 1043: 104-10, 2005 Jun.
Article in English | MEDLINE | ID: mdl-16037228

ABSTRACT

Blue pigments (blue-M1 and blue-M2) and red pigments (red-M1 and red-M2) were generated in a xylose-glycine reaction system. Blue-M2 was identified as an addition compound of di-xylulose-glycine to blue-M1 that involved two pyrrolopyrrole structures. We identified red pigments as isomers of addition compounds of xylulose-glycine to the condensed compound between pyrrolopyrrole-2-carbaldehyde and pyrrole-2-carbaldehyde. These pigments have polymerizing activity, suggesting that they are important Maillard reaction intermediates through the formation of melanoidins. Melanoidins induced IFN-gamma and IL-12 expression in spleen cells exposed to allergen and in macrophages, respectively. These findings suggest that melanoidins have a suppressive effect on allergic reaction as a novel physiological effect. On the other hand, we identified a glyceraldehyde-derived advanced glycation end product (AGE) formed from glyceraldehyde and N-acetylarginine as well as glyceraldehyde-derived pyridinium (GLAP) in physiological conditions. The AGE was identified as 5-methylimidazoline-4-one (MG-H1), which has been reported to be formed from arginine and methylglyoxal. GLAP, which induced reactive oxygen species (ROS) production in HL-60 cells, is supposed to be a toxic AGE, while MG-H1 is a nontoxic AGE.


Subject(s)
Glycation End Products, Advanced/chemistry , Glyceraldehyde , Polymers/chemistry , Pyridinium Compounds , Glycine , HL-60 Cells , Humans , Oxidative Stress/drug effects , Polymers/pharmacology , Reactive Oxygen Species , Xylose
11.
Biosci Biotechnol Biochem ; 68(2): 333-40, 2004 Feb.
Article in English | MEDLINE | ID: mdl-14981296

ABSTRACT

We demonstrated the cytotoxicity of glyceraldehyde-related Maillard reaction products for HL-60 cells. Glyceraldehyde-modified bovine serum albumin and glyceraldehyde-modified casein inhibited the proliferation of HL-60 cells. The reaction products formed from glyceraldehyde and Nalpha-acetyllysine had also a cytotoxic effect on HL-60 cells. The cytotoxic effect was prevented by N-acetylcysteine or pyrrolidinedithiocarbamate as the antioxidants. In addition, the reaction products depressed the intracellular glutathione level, and induced the reactive oxygen species (ROS) production. These results suggested that the glyceraldehyde-related advanced glycation end products (AGEs) induced the cytotoxicity and the oxidative stress. We previously reported that the glyceraldehyde-related AGE was identified as 1-(5-acetylamino-5-carboxypentyl)-3-hydroxy-5-hydroxymethyl-pyridinium, named GLAP (glyceraldehyde-derived pyridinium compound), formed from glyceraldehyde and Nalpha-acetyllysine (Biosci. Biotechnol. Biochem., 67, 930-932 (2003)). In this study, GLAP inhibited the proliferation of HL-60 cells, and the inhibitory effect was prevented by the antioxidants. Furthermore, GLAP depressed the intracellular glutathione level, and induced the ROS production. This work indicated the possibility that the cytotoxicity and the oxidative stress in the progression of diabetic complications and chronic renal disease might be induced by GLAP.


Subject(s)
Glyceraldehyde/chemistry , Glyceraldehyde/toxicity , Lysine/analogs & derivatives , Maillard Reaction , Oxidative Stress/drug effects , Antioxidants/pharmacology , Cell Survival/drug effects , Chromatography, High Pressure Liquid , Glutathione/metabolism , Glyceraldehyde/isolation & purification , HL-60 Cells , Humans , Immunohistochemistry , Lysine/chemistry , Pyridinium Compounds/chemistry , Pyridinium Compounds/isolation & purification , Pyridinium Compounds/toxicity , Reactive Oxygen Species/metabolism , Serum Albumin, Bovine/chemistry
12.
Biosci Biotechnol Biochem ; 68(1): 247-9, 2004 Jan.
Article in English | MEDLINE | ID: mdl-14745194

ABSTRACT

Blue-M1 is a blue pigment formed from xylose and glycine in the Maillard reaction. Previous work revealed that Blue-M1 scavenged hydroxyl radicals, and prevented the autoxidation of linoleic acid in vitro. We investigated the protective effect of Blue-M1 for 2,2'-azobis(2-amidino-propane)dihydrochloride (AAPH)-induced toxicity in COS-1 cells. COS-1 cells were cultured in AAPH containing DMEM medium with or without Blue-M1 at 37 degrees C for 24 h. Blue-M1 decreased the AAPH-induced toxicity in COS-1 cells, and this effect was dose-dependent. Furthermore, COS-1 cells were treated with diphenyl-1-pyrenylphosphine (DPPP), as a reagent for the detection of lipid peroxide, and then were cultured in AAPH containing DMEM medium with or without Blue-M1 at 37 degrees C for 6 h. Blue-M1 prevented the AAPH-induced peroxidation of cell membrane on COS-1 cells, and this effect was also dose-dependent. These results suggest that Blue-M1 prevents the oxidative cell injury. Therefore, Blue-M1 will be an antioxidant, which protect against the oxidative stress in living systems.


Subject(s)
Antioxidants/pharmacology , Glycerol/analogs & derivatives , Glycerol/pharmacology , Pyrroles/pharmacology , Amidines/pharmacology , Animals , COS Cells/drug effects , Cell Survival/drug effects , Lipid Peroxidation/drug effects , Maillard Reaction , Oxidative Stress
13.
Biofactors ; 21(1-4): 391-4, 2004.
Article in English | MEDLINE | ID: mdl-15630233

ABSTRACT

Protein is modified by carbonyl compound in the Maillard reaction, and the irreversible structure is formed as the advanced glycation end product (AGE). We identified GLAP (glyceraldehyde-derived pyridinium compound) as an AGE formed from glyceraldehyde and lysine residue of protein. In the present study, we investigated detection and determination of GLAP from glycated protein using fluorescence HPLC method. Albumin (BSA) and carbonyls (glyceraldehyde, glycolaldehyde, methylglyoxal, glyoxal, three pentoses or three hexoses) were dissolved in phosphate buffed solution (pH 7.4), and incubated at 37 degrees C for a week. GLAP was formed only in the glyceraldehyde-modified BSA. It is suggested that GLAP was specific AGE derived from glyceraldehyde. In addition, GLAP depressed the intracellular glutathione level and induced the reactive oxygen species (ROS) in HL-60 cells. GLAP caused the oxidative stress. Therefore, GLAP will be a biomarker in the AGE related disease such as diabetic complications or chronic renal failure.


Subject(s)
Glycation End Products, Advanced/analysis , Glycation End Products, Advanced/metabolism , Glyceraldehyde/metabolism , Cell Line, Tumor , Chromatography, High Pressure Liquid , HL-60 Cells , Humans , Lysine , Oxidative Stress , Serum Albumin, Bovine/chemistry
14.
Biosci Biotechnol Biochem ; 67(4): 930-2, 2003 Apr.
Article in English | MEDLINE | ID: mdl-12784645

ABSTRACT

Glyceraldehyde (200 mM) and N alpha-acetyllysine (100 mM) were incubated in 0.2 M sodium phosphate buffer (pH 7.4) at 37 degrees C for a week. A major compound, glyceraldehyde-related Maillard reaction product, was purified from the reaction mixture using reverse phase (ODS)-HPLC. It was identified as 1-(5-acetylamino-5-carboxypentyl)-3-hydroxy-5-hydroxymethyl-pyridinium, named as GLAP (Glyceraldehyde derived Pyridinium compound), using NMR and MS analyses. It was suggested that GLAP as a novel advanced glycation end product (AGE) is one of the key compounds in the glyceraldehyde-related Maillard reaction.


Subject(s)
Glycation End Products, Advanced/isolation & purification , Maillard Reaction , Pyridinium Compounds/isolation & purification , Chromatography, High Pressure Liquid , Glycation End Products, Advanced/chemistry , Glyceraldehyde/chemistry , Molecular Structure , Pyridinium Compounds/chemistry
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