Showing papers on "Methylglyoxal published in 1999"
TL;DR: Alpha-Oxoaldehydes were formed in early glycation from the degradation of glucose and Schiff's base adduct, which suggests that short periods of hyperglycaemia, as occur in impaired glucose tolerance, may be sufficient to increase the concentrations of alpha-oxoaldeHydes in vivo.
Abstract: The glycation of proteins by glucose has been linked to the development of diabetic complications and other diseases. Early glycation is thought to involve the reaction of glucose with N-terminal and lysyl side chain amino groups to form Schiff's base and fructosamine adducts. The formation of the alpha-oxoaldehydes, glyoxal, methylglyoxal and 3-deoxyglucosone, in early glycation was investigated. Glucose (50 mM) degraded slowly at pH 7.4 and 37 degrees C to form glyoxal, methylglyoxal and 3-deoxyglucosone throughout a 3-week incubation period. Addition of t-BOC-lysine and human serum albumin increased the rate of formation of alpha-oxoaldehydes - except glyoxal and methylglyoxal concentrations were low with albumin, as expected from the high reactivity of glyoxal and methylglyoxal with arginine residues. The degradation of fructosyl-lysine also formed glyoxal, methylglyoxal and 3-deoxyglucosone. alpha-Oxoaldehyde formation was dependent on the concentration of phosphate buffer and availability of trace metal ions. This suggests that alpha-oxoaldehydes were formed in early glycation from the degradation of glucose and Schiff's base adduct. Since alpha-oxoaldehydes are important precursors of advanced glycation adducts, these adducts may be formed from early and advanced glycation processes. Short periods of hyperglycaemia, as occur in impaired glucose tolerance, may be sufficient to increase the concentrations of alpha-oxoaldehydes in vivo.
1,116 citations
TL;DR: Uremia may be described as a state of carbonyl overload or "carbonyl stress" resulting from either increased oxidation of carbohydrates and lipids (oxidative stress) or inadequate detoxification or inactivation of reactive carbonyL compounds derived from both carbohydrates andlipids by oxidative and nonoxidatives.
518 citations
TL;DR: A comprehensive overview of methylglyoxal research, extending discussion from chemistry to biological implications by reviewing some important characteristics of methyl glyoxal metabolism and toxicity in a wide variety of species, and emphasizing the action of methyl-oxoaldehyde production in the environment as a potential risk factor and to the possible role of this a-dicarbonyl in diseases as discussed by the authors.
483 citations
TL;DR: The results suggest that argpyrimidine may contribute to the progression of not only long term diabetic complications, such as nephropathy and atherosclerosis, but also the tissue injury caused by ischemia/reperfusion.
379 citations
TL;DR: In both diabetic and uremic patients, these dicarbonyl compounds promote AGE accumulation in vivo, and especially in uremi patients, increased accumulation of GO could result from accelerating oxidative stress.
270 citations
TL;DR: An important role of glyoxalase I is suggested in conferring tolerance to plants under stress conditions by showing that the tolerance to different salt concentrations was correlated with the degree of Gly I expression.
Abstract: Despite its ubiquitous presence, the role of glyoxalase I has not been well investigated in plants. In order to find out its physiological functions, we have cloned and characterized a cDNA from Brassica juncea encoding glyoxalase I (Gly I) and made transgenic tobacco plants harbouring Gly I in both sense and antisense orientation. The transgenic nature of the plants was confirmed by Southern blotting, and the estimated number of genes inserted ranged from one to six. The transcript and protein levels of glyoxalase I were also monitored in transgenic plants. The expression of glyoxalase I in B. juncea was upregulated in response to salt, water and heavy metal stresses. In response to a high concentration of salt, the transcript level averaged threefold higher in 72 h, and an increase in the protein was also seen by immunoblotting. The transgenic plants over-expressing glyoxalase I showed significant tolerance to methylglyoxal and high salt, as tested in detached leaf disc senescence assay. A comparison of plants expressing high and low levels of glyoxalase I showed that the tolerance to different salt concentrations was correlated with the degree of glyoxalase I expression. Our results suggest an important role of glyoxalase I in conferring tolerance to plants under stress conditions.
258 citations
TL;DR: Impairment of α-oxoaldehyde detoxification is cytotoxic, and this may contribute to toxicity associated with GSH oxidation and S conjugation in oxidative stress and chemical toxicity, and to chronic pathogenesis associated with diabetes mellitus where there is oxidative stressand the formation of glyoxal, MG, and 3-DG is increased.
223 citations
TL;DR: The results suggest that besides its known antihyperglycemic effect, metformin could also decrease AGE formation by reacting with alpha-dicarbonyl compounds, relevant to a potential clinical use of met formin in the prevention of diabetic complications by inhibition of carbonyl stress.
223 citations
TL;DR: Vesperlysine A/LM-1 is a novel product of the advanced Maillard reaction in vivo and a specific marker of a diabetic process in the lens that is different from glyco- and lipoxidation.
178 citations
TL;DR: GDPs in PD fluids stimulate the production of vascular endothelial growth factor (VEGF), a factor known to enhance vascular permeability and angiogenesis, and VEGF production induced by GDPs may play a role in the progressive deterioration of the peritoneal membrane.
168 citations
TL;DR: The production of enantiomerically pure R-1,2-PD from glucose in Escherichia coli expressing NADH-linked glycerol dehydrogenase genes (E. coli gldA or Klebsiella pneumoniae dhaD) is reported and it is expected that R-3-PD production can be significantly improved through further metabolic and bioprocess engineering.
Abstract: 1,2-Propanediol (1,2-PD) is a major commodity chemical that is currently derived from propylene, a nonrenewable resource. A goal of our research is to develop fermentation routes to 1,2-PD from renewable resources. Here we report the production of enantiomerically pure R-1,2-PD from glucose in Escherichia coli expressing NADH-linked glycerol dehydrogenase genes (E. coli gldA or Klebsiella pneumoniae dhaD). We also show that E. coli overexpressing the E. coli methylglyoxal synthase gene (mgs) produced 1,2-PD. The expression of either glycerol dehydrogenase or methylglyoxal synthase resulted in the anaerobic production of approximately 0.25 g of 1,2-PD per liter. R-1,2-PD production was further improved to 0.7 g of 1,2-PD per liter when methylglyoxal synthase and glycerol dehydrogenase (gldA) were coexpressed. In vitro studies indicated that the route to R-1,2-PD involved the reduction of methylglyoxal to R-lactaldehyde by the recombinant glycerol dehydrogenase and the reduction of R-lactaldehyde to R-1,2-PD by a native E. coli activity. We expect that R-1,2-PD production can be significantly improved through further metabolic and bioprocess engineering.
TL;DR: The present study provides the first evidence that MG and 3DG are neurotoxic to cortical neurons in culture, and interference with the process by which glycation and AGEs formation occur may provide new therapeutic opportunities to reduce the pathophysiological changes associated with neurodegeneration.
Abstract: In this study, we investigate the neurotoxicity of glycation, particularly early-stage glycation, and its mechanisms, which are possibly synergized with oxidative stress. Methylglyoxal (MG) and 3-deoxyglucosone (3DG), intermediate products of glycation, are known to further accelerate glycation and advanced glycation endproducts (AGEs) formation. Both compounds showed neurotoxicity on cultured cortical neurons and these effects were associated with reactive oxygen species production followed by neuronal apoptosis. Pretreatment with N-acetylcysteine induced neuroprotection against MG and 3DG. Cotreatment, but not pretreatment, with aminoguanidine protected neurons against the neurotoxicities of both compounds. The present study provides the first evidence that MG and 3DG are neurotoxic to cortical neurons in culture. Interference with the process by which glycation and AGEs formation occur may provide new therapeutic opportunities to reduce the pathophysiological changes associated with neurodegeneration, if, as indicated here, the participation of glycoxidation in the pathogenesis of neurodegenerative diseases is essential.
TL;DR: This is the first demonstration that methylglyoxal modification of collagen can affect cell-matrix interactions and introduces a possible mechanism by which some of the deleterious changes in tissues with age and disease are occurring.
TL;DR: It is shown that CYP2E1 plays a vital role in the catabolism of acetone under fasting conditions, and the blood acetone levels after fasting for 48 hr were increased by 2.5- to 4-fold.
TL;DR: The α-diketones glyoxal, methylglyoxal and diacetyl were determined in selected beer and wine using a procedure involving the use of C18 solid phase extraction columns to remove interferences and derivatization of the compounds with o-phenylenediamine to form quinoxalines.
Abstract: The α-diketones glyoxal, methylglyoxal, and diacetyl were determined in selected beer and wine using a procedure involving the use of C18 solid phase extraction columns to remove interferences and derivatization of the compounds with o-phenylenediamine to form quinoxalines, which are separated by HPLC and detected using UV spectrophotometric detection. Interferences were more difficult to remove in the case of beer, due to the higher complexity of the matrix and because the concentrations of the compounds were lower (higher for methylglyoxal and lower for diacetyl, but all in the 10−7 M region). The determination was easier to implement in the case of wine as the typical concentrations of the compounds were about ten times higher, with methylglyoxal being the more abundant compound found.
TL;DR: A high-performance liquid chromatography procedure using 2,4-dinitrophenylhydrazine as a derivatizing agent is developed to determine endogenous formaldehyde, methylglyoxal, malondialdehyde, and acetaldehyde, and an increase in the excretion is confirmed in streptozotocin-induced diabetic rats.
Abstract: The deamination of methylamine and aminoacetone by semicarbazide-sensitive amine oxidase (SSAO) produces formaldehyde and methylglyoxal, respectively, which have been presumed to be involved in diabetic complications. A high-performance liquid chromatography procedure using 2,4-dinitrophenylhydrazine (DNPH) as a derivatizing agent is developed to determine endogenous formaldehyde, methylglyoxal, malondialdehyde, and acetaldehyde. The devised DNPH method is sensitive enough to analyze aldehyde levels in urine. An increase in the excretion of formaldehyde, methylglyoxal, and malondialdehyde is confirmed in streptozotocin-induced diabetic rats. Following the chronic administration of methylamine, the urinary levels of both formaldehyde and malondialdehyde (a product from lipid peroxidation) are found to be substantially increased. A potent selective SSAO inhibitor, (E)-2-(4-fluorophenethyl)-3-fluoroallylamine hydrochloride (MDL-72974A), reduced the formation of formaldehyde, methylglyoxal, and malondialdehyde. The increase of the cytotoxic aldehyde levels as a result of increased SSAO-mediated deamination may occur in some pathological conditions.
TL;DR: A twofold reproducible increase in reporter activity was seen with insulin and ZnCl(2) treatments, indicating a functionally operative insulin response element and metal response element (MRE).
TL;DR: Preincubation of L1210 cells with 2(Et)2 increases the sensitivity of these cells to the inhibitory effects of exogenous methylglyoxal and is much less toxic to nonproliferating murine splenic lymphocytes, possibly reflecting reduced sensitivity to methylgly oxal and/or reduced chemical stability of the diacid inside these cells.
Abstract: S-(N-Aryl-N-hydroxycarbamoyl)glutathione derivatives (GSC(O)N(OH)C6H4X, where GS = glutathionyl and X = H (1), Cl (2), Br (3)) have been proposed as possible anticancer agents, because of their ability to strongly inhibit the methylglyoxal-detoxifying enzyme glyoxalase I. In order to test this hypothesis, the in vitro antitumor activities of these compounds and their [glycyl,glutamyl] diethyl ester prodrug forms (1(Et)2-3(Et)2) have been examined. All three diethyl esters inhibit the growth of L1210 murine leukemia and B16 melanotic melanoma in culture, with GI50 values in the micromolar concentration range. Cell permeability studies with L1210 cells indicate that growth inhibition is associated with rapid diffusion of the diethyl esters into the cells, followed by enzymatic hydrolysis of the ethyl ester functions to give the inhibitory diacids. In contrast, the corresponding diacids neither readily diffuse into nor significantly inhibit the growth of these cells. Consistent with the hypothesis that cell growth inhibition is due to competitive inhibition of glyoxalase I, preincubation of L1210 cells with 2(Et)2 increases the sensitivity of these cells to the inhibitory effects of exogenous methylglyoxal. Compound 2(Et)2 is much less toxic to nonproliferating murine splenic lymphocytes, possibly reflecting reduced sensitivity to methylglyoxal and/or reduced chemical stability of the diacid inside these cells. Finally, a plasma esterase-deficient murine model has been identified that should allow in vivo testing of the diethyl esters.
TL;DR: Chronic intake of methylglyoxal, at levels that could be attained in food, is toxic by depletion of blood GSH and could have adverse effect on some GSH dependent functions in vivo.
TL;DR: It was observed in previous assays that methylglyoxal formed via deamination of aminoacetone was quite unstable and led to erroneous results, so o-Phenylenediamine (o-PD) was employed for derivatization of methylglyxal and o-PD does not affect SSAO activity and can be included in the enzyme reaction mixture for continuous trapping of methyl glyoxal.
TL;DR: Each sugar exhibited unique characteristics in the modification of lens proteins by glycation, and incubation with 3-deoxyxylosone resulted in extensive loss of Lys and Arg residues, a higher extent of Lys or Arg crosslinking and significant fluorophore formation.
TL;DR: Results demonstrate that the recombinant S. cerevisiae cells permeabilized with alcohol solutions under the optimum condition are very effective whole cell biocatalysts.
Abstract: The permeabilization of yeast cells with methanol, ethanol, and isopropyl alcohol under various conditions was studied to develop the preparation method of high activity whole cell biocatalysts. Recombinant Saccharomyces cerevisiae, which intracellularly overexpresses glyoxalase I and catalyzes the conversion of methylglyoxal to S-lactoylglutathione in the presence of glutathione, was used as the model system. The permeabilization treatments with alcohols significantly enhanced the activities of yeast cells. Especially, the initial S-lactoylglutathione production rates of cells permeabilized with 40% ethanol and isopropyl alcohol solutions for 10 min at 4 degrees C were high and were 364 and 582 times larger than those of untreated cells, respectively. These permeabilized yeast cells retained high activities during repeated batch reactions. Even in third batch reaction, they showed approximately 70-80% of the activity in the first batch. The plasma membrane of S. cerevisiae cells was damaged by the treatment with alcohol solutions in such a way that leakage of glyoxalase I from the cells is rather small and that both substrate and product show very high permeability. The initial S-lactoylglutathione production rates of these permeabilized cells were 1.5-2.5 times larger than those of glyoxalase I in cell extracts prepared by ethyl acetate method from the same amount of cells. These results demonstrate that the recombinant S. cerevisiae cells permeabilized with alcohol solutions under the optimum condition are very effective whole cell biocatalysts. Copyright 1999 John Wiley & Sons, Inc.
TL;DR: The crystal structure of MGS bound to formate and substoichiometric amounts of phosphate in the space group P6522 shows that the enzyme is a homohexamer composed of interacting five-stranded beta/alpha proteins, rather than the hallmark alpha/beta barrel structure of TIM.
TL;DR: The target compound, γ -(L-γ-azaglutamyl)-S-( p -bromobenzyl)-L-cysteinylglycine 6 , was a potent inhibitor of glyoxalase I with almost no loss of activity when compared to PBBG.
TL;DR: It is suggested that the metabolism of methylglyoxal to d-lactate causes β-cell swelling and activation of the volume-sensitive anion channel, leading to depolarization, which could be relevant to the stimulatory action of d-glucose.
Abstract: Membrane potential and whole-cell current were studied in rat pancreatic β-cells using the `perforated patch' technique and cell volume measured by a video-imaging method. Exposure of β-cells to the α-ketoaldehyde methylglyoxal (1 mm) resulted in depolarization and electrical activity. In cells voltage-clamped at −70 mV, this effect was accompanied by the development of inward current noise. In voltage-pulse experiments, methylglyoxal activated an outwardly rectifying conductance which was virtually identical to the volume-sensitive anion conductance previously described in these cells. Two inhibitors of this conductance, 4,4′-dithiocyanatostilbene-2,2′-disulfonic acid (DIDS) and 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB), also inhibited the depolarization and inward current evoked by methylglyoxal. Methylglyoxal increased β-cell volume to a relative value of 1.33 after 10 min with a gradual return towards basal levels following withdrawal of the α-ketoaldehyde. None of the effects of methylglyoxal was observed in response to t-butylglyoxal which, unlike methylglyoxal, is a poor substrate for the glyoxalase pathway. Methylglyoxal had no apparent effect on β-cell K+ channel activity. It is suggested that the metabolism of methylglyoxal to d-lactate causes β-cell swelling and activation of the volume-sensitive anion channel, leading to depolarization. These findings could be relevant to the stimulatory action of d-glucose, the metabolism of which generates significant quantities of l-lactate.
TL;DR: The bidentate nucleophile, phenylacylthiazolium bromide (PTB), was found to protect and allow the growth of E. coli cells in the presence of either externally added or endogenously produced MG, suggesting that PTB could interact with and detoxify MG.
Abstract: Dicarbonyl-containing compounds such as methylglyoxal (MG) are toxic to cells since they can interact with the nucleophilic centers of macromolecules. MG has been found to accumulate during hypergl...
01 Jan 1999
TL;DR: It is hypothesized that yeast glyoxalase I evolved by gene duplication and here show supporting evidence that it is induced by osmotic stress through the HOG-MAG kinase signaling pathway in S. cerevisiae.
Abstract: Methylglyoxal is an endogenous cytotoxic compound formed as a byproduct of glycolysis. We systematically analyzed the metabolic fate of methylglyoxal in various microorganisms and found that glyoxalase I is a ubiquitous and critical enzyme for its detoxification. We found that glyoxalase I consists of five segments (regions I-V) which are conserved among the glyoxalase Is of various species. We hypothesize that yeast glyoxalase I evolved by gene duplication and here show supporting evidence. We also found that expression of the structural gene for the glyoxalase I of S. cerevisiae is induced by osmotic stress through the HOG-MAG kinase signaling pathway. We identified the physiological significance of this glycolytic-methylglyoxal pathway in S. cerevisiae.
TL;DR: Results suggest that in addition to reducing the growth rates, MGBCP can induce apoptotic cell death in this human hepatocellular carcinoma cell line.
Abstract: The antitumor effects of a polyamine biosynthetic pathway inhibitor methylglyoxal bis(cyclopentylamidinohydrazone) (MGBCP) on the human hepatocellular carcinoma SK-HEP-1 cell line have been investigated. The growth of these cultured hepatocellular carcinoma cells was inhibited by MGBCP in a dose-dependent manner. Spermidine and spermine levels were dose-dependently depressed, and morphological changes due to programmed cell death (apoptosis) were observed in these MGBCP-treated hepatocellular carcinoma cells. These results suggest that in addition to reducing the growth rates, MGBCP can induce apoptotic cell death in this human hepatocellular carcinoma cell line.
01 Jan 1999