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Showing papers on "Methylglyoxal published in 2002"


Journal ArticleDOI
TL;DR: This study demonstrates an elevated methylglyoxal level and advanced glycation end products in cells from hypertensive rats, and methyl glyoxal increases oxidative stress, activates NF-&kgr;B, and enhances ICAM-1 expression.
Abstract: Methylglyoxal can yield advanced glycation end products via nonenzymatic glycation of proteins. Whether methylglyoxal contributes to the pathogenesis of hypertension has not been clear. The aim of the present study was to investigate whether the levels of methylglyoxal and methylglyoxal-induced advanced glycation end products were enhanced and whether methylglyoxal increased oxidative stress, activated nuclear factor-kappaB (NF-kappaB), and increased intracellular adhesion molecule-1 (ICAM-1) content in vascular smooth muscle cells from spontaneously hypertensive rats. Basal cellular levels of methylglyoxal and advanced glycation end products were more than 2-fold higher (P<0.05) in cells from hypertensive rats than from normotensive Wistar-Kyoto rats. This correlated with levels of oxidative stress and oxidized glutathione that were significantly higher in cells from hypertensive rats, whereas levels of glutathione and activities of glutathione reductase and glutathione peroxidase were significantly lower. Basal levels of nuclearly localized NF-kappaB p65 and ICAM-1 protein expression were higher in cells from hypertensive rats than from normotensive rats. Addition of exogenous methylglyoxal to the cultures induced a greater increase in oxidative stress and advanced glycation end products in cells from hypertensive rats compared with normotensive rats and significantly decreased the activities of glutathione reductase and glutathione peroxidase in cells of both rat strains. Methylglyoxal activated NF-kappaB p65 and increased ICAM-1 expression in hypertensive cells, which was inhibited by N-acetylcysteine. Our study demonstrates an elevated methylglyoxal level and advanced glycation end products in cells from hypertensive rats, and methylglyoxal increases oxidative stress, activates NF-kappaB, and enhances ICAM-1 expression. Our findings suggest that that elevated methylglyoxal and associated oxidative stress possibly contribute to the pathogenesis of hypertension.

226 citations


Book ChapterDOI
TL;DR: It is probable that high intracellular glucose concentration is an important trigger for increased glycation, leading to increased formation of methylglyoxal, gly oxal, and 3-deoxyglucosone that glycate proteins to form AGEs intrACEllularly and extracellularly.
Abstract: Glycation is the nonenzymatic reaction of glucose, alpha-oxoaldehydes, and other saccharide derivatives with proteins, nucleotides, and lipids. Early glycation adducts (fructosamines) and advanced glycation adducts (AGEs) are formed. "Glycoxidation" is a term used for glycation processes involving oxidation. Sural, peroneal, and saphenous nerves of human diabetic subjects contained AGEs in the perineurium, endothelial cells, and pericytes of endoneurial microvessels and in myelinated and unmyelinated fibres localized to irregular aggregates in the cytoplasm and interstitial collagen and basement membranes. Pentosidine content was increased in cytoskeletal and myelin protein extracts of the sural nerve of human subjects and cytoskeletal proteins of the sciatic nerve of streptozotocin-induced diabetic rats. AGEs in the sciatic nerve of diabetic rats were decreased by islet transplantation. Improved glycemic control of diabetic patients may be expected to decrease protein glycation in the nerve. Protein glycation may decrease cytoskeletal assembly, induce protein aggregation, and provide ligands for cells surface receptors. The receptor for advanced glycation and products (RAGE) was expressed in peripheral neurons. It is probable that high intracellular glucose concentration is an important trigger for increased glycation, leading to increased formation of methylglyoxal, glyoxal, and 3-deoxyglucosone that glycate proteins to form AGEs intracellularly and extracellularly. Oxidative stress enhances these processes and is, in turn, enhanced by AGE/RAGE interactions. An established therapeutic strategy to prevent glycation is the use of alpha-oxoaldehyde scavengers. Available therapeutic options for trial are high-dose nicotinamide and thiamine therapies to prevent methylglyoxal formation. Future possible therapeutic strategies are RAGE antagonists and inducers of the enzymatic antiglycation defense. More research is required to understand the role of glycation in the development of diabetic neuropathy.

220 citations


Journal ArticleDOI
TL;DR: The significantly higher concentrations of the latter materials over the former in diabetic plasma and cells lead us to suggest that alterations in the activity of key cellular enzymes induced by glycated proteins may play a significant role in the development of diabetic complications.

201 citations


Journal ArticleDOI
TL;DR: The first unequivocal identification of the lysine-arginine cross-links glucosepane 5, DOGDIC 6, MODIC 7, and GODIC 8 in human material is reported on, appearing predestined as markers for pathophysiological processes.

195 citations


Journal ArticleDOI
TL;DR: The studies show that pyridoxamine reduces oxidative stress and AGE formation and suspect that a direct interaction of pyrIDoxamine with MG partly accounts for AGE inhibition.

171 citations


Journal ArticleDOI
TL;DR: The early and advanced glycation adduct contents of these proteins were investigated using the 6-aminoquinolyl-N-hydroxysuccinimidyl-carbamate (AQC) chromatographic assay of enzymic hydrolysates and most AGEs in albumin glycated minimally by methylglyoxal and glucose were identified.
Abstract: Glycation of proteins leads to the formation of advanced glycation endproducts (AGEs) of diverse molecular structure and biological function. Serum albumin derivatives modified to minimal and high extents by methylglyoxal and glucose in vitro have been used in many studies as model AGE proteins. The early and advanced glycation adduct contents of these proteins were investigated using the 6-aminoquinolyl-N-hydroxysuccinimidyl-carbamate (AQC) chromatographic assay of enzymic hydrolysates. AGEs derived from methylglyoxal, glyoxal and 3-deoxyglucosone, the hydroimidazolones N(delta)-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1), N(delta)-(5-hydro-4-imidazolon-2-yl)ornithine (G-H1) and N(delta)-[5-(2,3,4-trihydroxybutyl)-5-hydro-4-imidazolon-2-yl]ornithine (3DG-H1), bis(lysyl)imidazolium cross-links methylglyoxal-derived lysine dimer (MOLD), glyoxal-derived lysine dimer (GOLD), 3-deoxyglucosone-derived lysine dimer (DOLD), monolysyl adducts N(epsilon)-(1-carboxyethyl)lysine (CEL), N(epsilon)-carboxymethyl-lysine (CML) and pyrraline, other AGEs, N(delta)-(4-carboxy-4,6-dimethyl-5,6-dihydroxy-1,4,5,6-tetrahydropyrimidin-2-yl)ornithine (THP), argpyrimidine and pentosidine, and fructosyl-lysine were determined. AGEs with intrinsic fluorescence (argpyrimidine and pentosidine) were assayed without derivatization. Human serum albumin (HSA) glycated minimally by methylglyoxal in vitro contained mainly MG-H1 with minor amounts of THP and argpyrimidine. Similar AGEs were found in prothrombin glycated minimally by methylglyoxal and in N(alpha)-t-butyloxycarbonyl-arginine incubated with methylglyoxal. HSA glycated highly by methylglyoxal contained mainly argpyrimidine, MG-H1 and THP, with minor amounts of CEL and MOLD. HSA glycated minimally by glucose in vitro contained mainly fructosyl-lysine and CML, with minor amounts of THP, MG-H1, G-H1, 3DG-H1, argpyrimidine and DOLD. HSA glycated highly by glucose contained these AGEs and pyrraline, and very high amounts ( approximately 8 mol/mol of protein) of fructosyl-lysine. Most AGEs in albumin glycated minimally by methylglyoxal and glucose were identified. Significant proportions of arginine and lysine-derived AGEs in albumin modified highly by methylglyoxal, and lysine-derived AGEs in albumin modified highly by glucose, remain to be identified.

152 citations


Journal ArticleDOI
TL;DR: Heat-shock protein 27 (Hsp27) is identified as a major MG-modified protein in cells that causes sensitization of the cells to anti-tumor drug-induced apoptosis and is a novel modulator of cell survival by directly incorporating with the specific protein residue.

133 citations


Journal ArticleDOI
TL;DR: It is postulate that modification of GAPDH by environmental factors or genetic dysregulation and the resultant differences in MG production could at least partially account for the wide varying rates of progression of diabetic complications seen among individuals.

123 citations


Journal ArticleDOI
TL;DR: It is reported that TNF induces an increased phosphorylation of glyoxalase I that is mediated by protein kinase A and required for cell death and shown that MG modification of proteins is a targeted process and that MG may thus function as a signal molecule during the regulation of cell death.
Abstract: Tumor necrosis factor (TNF)-induced cell death in the fibrosarcoma cell line L929 is a caspase-independent process that is characterized by increased production of reactive oxygen species (ROS) in the mitochondria. To elucidate this ROS-dependent cell death pathway, a comparative study of the phosphoproteins present in TNF-treated and control cells was performed. Here we report that TNF induces an increased phosphorylation of glyoxalase I that is mediated by protein kinase A and required for cell death. We also show that TNF induces a substantial increase in intracellular levels of methylglyoxal (MG) that leads to the formation of a specific MG-derived advanced glycation end product and that this formation occurs as a consequence of increased ROS production. These data indicate that MG modification of proteins is a targeted process and that MG may thus function as a signal molecule during the regulation of cell death. Furthermore, we provide evidence that the TNF-induced phosphorylation of glyoxalase I is not involved in detoxification of MG by means of the glyoxalase system, but that phosphorylated glyoxalase I is on the pathway leading to the formation of a specific MG-derived advanced glycation end product.

110 citations


Journal ArticleDOI
TL;DR: It is demonstrated that MGO has an inhibitory effect on both the tricarboxylic acid cycle and the electron respiratory chain, which appears to be specific to certain mitochondrial proteins.
Abstract: Chronic hyperglycemia has been linked to alterations in mitochondrial function, suggesting an important role in the pathophysiology of the complications of diabetes mellitus. In the diabetic kidney, ultrastructural changes in mitochondria are associated with impaired tubular function. The goal of this study was to determine if methylglyoxal (MGO), a dicarbonyl compound reaching high levels in hyperglycemic conditions, has direct toxicity for renal mitochondria. Intact mitochondria isolated from the renal cortex of rats were incubated with MGO to determine 1) its effect on mitochondrial respiration, 2) the conditions under which MGO exerts these effects, and 3) the potential mitochondrial targets of MGO influence. This study demonstrates that MGO has an inhibitory effect on both the tricarboxylic acid cycle and the electron respiratory chain. The modifications appear to be specific to certain mitochondrial proteins. Alterations of these proteins lead to disturbances in mitochondria that may play an important role in renal cellular toxicity and in the development of diabetic nephropathy.

106 citations


Journal ArticleDOI
TL;DR: This research qualifies α-amino-β-mercapto-β,β-dimethyl-ethane as a promising pharmacophore for the development of related α-dicarbonyl scavengers as therapeutic agents to protect cells against carbonyl stress.

Journal ArticleDOI
TL;DR: MGO synergistically enhances cisplatin-induced apoptosis through activation of PKCδ and that PKC δ is critical to both cell death and cell survival pathways.

Journal ArticleDOI
TL;DR: A system of whole plasma glycation over 16 h with micromolar concentrations of MG, coupled with the measurement of activities of plasminogen and AT III by specific substrates provides a straightforward, practical method for monitoring the action of putative antiglycation agents.

Journal ArticleDOI
TL;DR: A novel mechanism for the oxidative modification of proteins in diabetes is proposed, namely the oxidative deamination of the lysine residue via the Maillard reaction.
Abstract: The levels of alpha-aminoadipic-delta-semialdehyde residue, the oxidative deamination product of lysine residue, in plasma protein from streptozotocin-induced diabetic rats were evaluated. alpha-Aminoadipic-delta-semialdehyde was converted to a bisphenol derivative by acid hydrolysis in the presence of phenol, and determined by high performance liquid chromatography. Analysis of plasma proteins revealed three times higher levels of alpha-aminoadipic-delta-semialdehyde in diabetic subjects compared with normal controls. Furthermore, we explored the oxidative deamination via the Maillard reaction and demonstrated that the lysine residue of bovine serum albumin is oxidatively deaminated during the incubation with various carbohydrates in the presence of Cu2+ at a physiological pH and temperature. This experiment showed that 3-deoxyglucosone and methylglyoxal are the most efficient oxidants of the lysine residue. When the reaction was initiated from glucose, a significant amount of alpha-aminoadipic-delta-semialdehyde was also formed in the presence of Cu2+. The reaction was significantly inhibited by deoxygenation, catalase, and a hydroxyl radical scavenger. The mechanism we propose for the oxidative deamination is the Strecker-type reaction and the reactive oxygen species-mediated oxidation. Based on these findings, we propose a novel mechanism for the oxidative modification of proteins in diabetes, namely the oxidative deamination of the lysine residue via the Maillard reaction.

Journal ArticleDOI
TL;DR: Observations indicated that substrate-induced induction of AR by MG during hyperglycemic conditions may hinder vascular remodeling and accelerate the development of vascular lesions in diabetes.
Abstract: Methylglyoxal (MG), a reactive dicarbonyl produced during glucose metabolism, induced a dose- and time-dependent increase in aldose reductase (AR) mRNA level in rat aortic smooth muscle cells (SMCs). AR has been implicated in the pathogenesis of diabetic complications, whereas the clinical efficacy of AR inhibitors has not been unequivocally proven. The enzyme catalyzes the reduction of glucose in the polyol pathway, as well as that of MG, which is known to be a preferred substrate of AR. A maximum of 4.5-fold induction of AR mRNA by MG was accompanied by elevated enzyme activity and protein levels and was completely abolished in the presence of cycloheximide or actinomycin D. Pretreatment of SMCs with N-acetyl-L-cysteine significantly suppressed the MG-induced AR expression, whereas DL-buthionine-(S,R)-sulfoximine further augmented the MG-induced increase in AR mRNA level. Intracellular levels of reactive oxygen species determined using 2',7'-dichlorofluorescein diacetate were significantly elevated in SMCs treated with MG, suggesting the involvement of oxidative stress in this process. However, inconsistent with our previous findings on oxidative stress-induced up-regulation of AR, the inhibition of extracellular signal-regulated kinase by 2'-amino-3'-methoxyflavone (PD98059) did not affect MG-induced AR expression, whereas blockade of the p38 mitogen-activated protein kinase pathway by 4-(4-fluorophenyl)-2-(4-methylsulfonylphenyl)-5-(4-pyridyl) imidazol (SB203580) significantly suppressed the induction. The cytotoxic effect of MG on SMCs was significantly enhanced in the presence of the AR inhibitor ponalrestat, indicating a protective role of AR against MG-induced cell damage. Taken together, these observations indicated that substrate-induced induction of AR by MG during hyperglycemic conditions may hinder vascular remodeling and accelerate the development of vascular lesions in diabetes.

Journal ArticleDOI
TL;DR: Reactive intermediates such as glucosone, 3-deoxyglucos one, methylglyoxal, and glyoxal were formed upon heat treatment of glycated HSA at 100° C, indicating that these aldehydes generated from Amadori products by oxidative cleavage can contribute to further CML formation.

Journal ArticleDOI
TL;DR: Immunostaining of tissue sections showed that aminoacetone-treated rats (normal as well as diabetic) formed more argpyrimidine in aortic smooth muscle than untreated controls, suggesting that SSAO can enhance AGE synthesis in the macrovasculature of diabetic individuals by production of MG.

Journal ArticleDOI
TL;DR: Important caveats of the widely used dichlorofluorescein assay are revealed and methods other than the microtiter plate assay are needed to accurately assess cellular oxidant stress in presence of native or modified albumin.

Journal ArticleDOI
TL;DR: GLO I together with GSH efficiently lowers glucose-derived RCOs, especially GO and MGO, both in conventional glucose PD fluids and in RCO solutions, suggesting that maneuvers raising GLO I activity inperitoneal cells or in the peritoneal cavity might help prevent the deleterious effects of thePeritoneal carbonyl stress in PD patients.

Journal ArticleDOI
TL;DR: The effects of thermal denaturation on the susceptibility of protein glycation was examined using glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and aspartate aminotransferase (AAT) as target proteins to hypothesized that denatured protein may provide a more susceptible target for glycation, which is a known mediator of inflammation.

Journal ArticleDOI
Peter H. Yu1, Wang M1, Deng Yl1, Fan H1, Shira-Bock L1 
TL;DR: Increased semicarbazide-sensitive amine oxidase–mediated deamination could be involved in the cascade of atherogenesis related to diabetic complications.
Abstract: Aims/hypothesis. Semicarbazide-sensitive amine oxidase has been recognised to be a potential risk factor in vascular disorders associated with diabetic complications and to be related to mortality in patients suffering from heart disease. This enzyme, associated with the vascular system, catalyses the deamination of methylamine and aminoacetone, and also acts as an adhesion molecule related to leucocyte trafficking and inflammation. The deaminated products include the toxic aldehydes, formaldehyde and methylglyoxal, respectively, hydrogen peroxide and ammonia.

Journal ArticleDOI
TL;DR: Inhibition of cell division decreased glyoxalase I activity and vice versa, thus further corroborating its role as a cell division marker enzyme, as well as confirming its role to stress tolerance as well.
Abstract: Glyoxalase I (EC 4.4.1.5) activity has long been associated with rapid cell proliferation, but experimental evidence is forthcoming, linking its role to stress tolerance as well. Proliferative callus cultures of groundnut (Arachis hypogaea L. cv. JL24) showed a 3.3-fold increase in glyoxalase I activity during the logarithmic growth phase, correlating well with the data on FW gain and mitotic index. Inhibition of cell division decreased glyoxalase I activity and vice versa, thus further corroborating its role as a cell division marker enzyme. Cell lines of A. hypogaea selected in the presence of high salt (NaCl) and herbicide (glyphosate) concentrations, yielded 4.2- to 4.5-fold and 3.9- to 4.6-fold elevated glyoxalase I activity, respectively, in a dose dependent manner reflective of the level of stress tolerance. The stress-induced increase in enzyme activity was also accompanied by an increase in the glutathione content. Exogenous supplementation of glutathione could partially alleviate the growth inhibition of callus cultures induced by methylglyoxal and d-isoascorbic acid, but failed to recover the loss in glyoxalase I activity due to d-isoascorbic acid. The adaptive significance of elevated glyoxalase I activity in maintaining glutathione homeostasis has been discussed in view of our understanding on the role of glutathione in the integration of cellular processes with plant growth and development under stress conditions.

Journal ArticleDOI
TL;DR: The role of the glyoxalases in detoxifying cytotoxic methylglyoxal (MG) in bladder cancer is confirmed and differing levels of GI activity level and gene expression between the SBC and IBC samples could help in their differential diagnosis.

Journal ArticleDOI
TL;DR: Gly-I may play a critical detoxifying role in glycolysis to maintain cellular activity and viability of prostatic cancer cells and N-acetylcysteine is an essential cofactor for Gly-I.
Abstract: A role of glyoxalase I (Gly-I), a detoxifying enzyme, in cell viability of prostate cancer was investigated. Cell extracts obtained from 66 prostate tissue specimens and prostatic cancer PC-3 cells were assayed for Gly-I activity using the spectrophotometric method. Gly-I activity was consistently more than eightfold higher in prostate cancer (CAP) specimens (n=37) than in non-cancerous (NCP) specimens (n=29). To understand the importance of such a high Gly-I activity in CAP specimens, the effects of methylglyoxal (MG) on PC-3 cells were examined in vitro. MG, a putative toxic glycolytic metabolite, was capable of inducing severe (>99%) cell death in 24 h, along with a significant reduction in activities of Gly-I as well as glyceraldehyde 3-phosphate dehydrogenase (G3PDH), a key glycolytic enzyme. However, such severe cell death was effectively (~85%) prevented with N-acetylcysteine (NAC), a precursor of reduced glutathione (GSH) that is an essential cofactor for Gly-I, accompanied by the intact Gly-I and G3PDH activities. Therefore, Gly-I may play a critical detoxifying role in glycolysis to maintain cellular activity and viability of prostatic cancer cells.

Journal ArticleDOI
TL;DR: A formation pathway for 2-acetylthiazole from methylglyoxal and cysteine is proposed, in which N-(2-sulfanylethyl)-2-oxopropanamide 1 is a new intermediate in Maillard-type reactions in systems under mild conditions.
Abstract: Under conditions close to those of wine, that is, low pH, aqueous medium, and low temperatures, this work describes N-(2-sulfanylethyl)-2-oxopropanamide (1), a new intermediate in the formation of 2-acetylthiazole from methylglyoxal and cysteine. 1 was characterized by MS, derivatization MS, and 1H and 13C NMR and was synthesized from 2-sulfanylethanamine and ethyl pyruvate. A formation pathway for 2-acetylthiazole from methylglyoxal and cysteine is proposed, in which 1 is a new intermediate in Maillard-type reactions in systems under mild conditions. Keywords: N-(2-Sulfanylethyl)-2-oxopropanamide; Maillard reaction; cysteine; 2-acetylthiazole; wine aroma

Journal ArticleDOI
TL;DR: The action of MGBG revealed that it has a non-specific effect on the whole polyamine metabolism of Scots pine and at certain concentrations it may induce plant differentiation as well.

Journal ArticleDOI
TL;DR: It is found that cytochrome c added to incubation mixtures containing guanidino compounds and methylglyoxal in phosphate buffer solution resulted in reduction of cy tochrome c, and interactions of various uremic retention products may generate reactive oxygen species and may be involved in the oxidative stress observed in CRF patients.
Abstract: Uremic toxins are accumulated in the blood of patients with chronic renal failure (CRF), although alteration of the toxicity by the interaction of various uremic retention products has not been precisely clarified. In this study, we found that cytochrome c added to incubation mixtures containing guanidino compounds and methylglyoxal in phosphate buffer solution (pH 7.4) resulted in reduction of cytochrome c. Superoxide anions were generated from incubation mixtures of each guanidino compound with methylglyoxal, because the reduction was inhibited by the addition of superoxide dismutase. The incubation mixture containing each guanidino compound and methylglyoxal had different rates of generation of the superoxide anion from other mixtures. A relatively higher superoxide anion formation rate was observed in the incubation mixture containing Arg and methylglyoxal (7.9 +/- 0.5nmol x m(-1) x min(-1)), or in the incubation mixture containing methylguanidine and methylglyoxal (6.3 +/- 0.6 nmol x ml(-1) min(-1)). These findings suggest that interactions of various uremic retention products which accumulate in the blood of uremic patients may generate reactive oxygen species and may be involved in the oxidative stress observed in CRF patients. The addition of aminoguanidine, which is known to inhibit the formation of advanced glycation end products, to a mixture of guanidino compounds and methylglyoxal inhibited reactions between guanidino compounds and methylglyoxal.

Journal ArticleDOI
TL;DR: Results obtained showed that alterations in lens proteins do not follow the specific reactivity of studied carbonyl compounds, despite the similarity in chemical structures of α‐oxoaldehydes and ascorbic acid degradation products.
Abstract: Cataract is generally associated with the breakdown of the lens microarchitecture Age-dependent chemical modifications and cross-linking of proteins are the major pathways for development of lens opacity The specific alterations in lens proteins caused by glycation with four carbonyl metabolites, fructose, methylglyoxal, glyoxal, and ascorbic acid, were investigated Decrease in intensity of tryptophan related fluorescence and level of reduced protein sulfhydryl groups, parameters that are indicative for changes in protein conformation, were observed after reaction with all studied carbonyl compounds Protein carbonyl content, an index for oxidative damage to proteins, was strongly enhanced in methylglyoxal-treated proteins Cross-linking of glycated proteins was confirmed by polyacrylamide electrophoresis alpha-Oxoaldehydes were the most reactive in protein aggregation They also formed specific chromophores absorbing UV light above 300 nm Significant loss in lactate dehydrogenase activity resulted from incubation with methylglyoxal, followed by glyoxal and ascorbic acid The results obtained showed that alterations in lens proteins do not follow the specific reactivity of studied carbonyl compounds Despite the similarity in chemical structures of alpha-oxoaldehydes and ascorbic acid degradation products, they cause specific alterations in lens protein structure with different biological consequences

Journal ArticleDOI
01 Nov 2002
TL;DR: In this paper, the rate of reaction of methylglyoxal with metformin, forming hydroimidazolone, triazepinone and other adducts at pH 7.4 and 37 °C in an initial rate study was examined.
Abstract: We examined the rate of reaction of methylglyoxal with metformin, forming hydroimidazolone, triazepinone and other adducts at pH 7.4 and 37 °C in an initial rate study. Metformin was not an efficient scavenger of methylglyoxal. Mechanisms other than the scavenging of methylglyoxal were probably responsible for decreased methylglyoxal concentration in diabetic subjects on metformin therapy—the lifting of insulin resistance, for example.

Journal ArticleDOI
TL;DR: The documented glycation-related photosensitization could explain the accelerated pathogenic changes in human lens at advanced age and under diabetic conditions.
Abstract: This study intends to clarify the ability of different carbonyl-containing lens metabolites to form advanced glycation end products, which possess photosensitizer activity and to investigate whether these modified proteins could be implicated in lens photodamage. Calf lens protein was experimentally glycated with either methylglyoxal, glyoxal, ascorbic acid, or fructose to obtain models of aged and diabetic cataractous lenses. Being exposed to 200 J/cm 2 UVA radiation the model glycated proteins produced 2-3-fold more singlet oxygen compared to the unmodified protein and the superoxide radical formation was 30-80% higher than by the native protein. Ascorbylated proteins demonstrated the highest photosensitizer activity. Biological responses of glycation-related photosensitizers were studied on cultured lens epithelial cells irradiated with 40 J/cm 2 UVA. Tissue culture studies revealed a significant increase in thiobarbituric acid reactive substances in the culture medium of lens epithelial cells after ir...