SEARCH · PubMed Health

Results for “Pyruvaldehyde”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 307 records · Page 17Linked to original sources

PubMed2006

Methylglyoxal modification of mSin3A links glycolysis to angiopoietin-2 transcription.

Methylglyoxal is a highly reactive dicarbonyl degradation product formed from triose phosphates during glycolysis. Methylglyoxal forms stable adducts primarily with arginine residues of intracellular proteins. The biologic role of this covalent modification in regulating cell function is not known. Here, we report that in retinal Müller cells, increased glycolytic flux causes increased methylglyoxal modification of the corepressor mSin3A. Methylglyoxal modification of mSin3A results in increased recruitment of O-GlcNAc transferase to an mSin3A-Sp3 complex, with consequent increased modification of Sp3 by O-linked N-acetylglucosamine. This modification of Sp3 causes decreased binding of the repressor complex to a glucose-responsive GC box in the angiopoietin-2 promoter, resulting in increased Ang-2 expression. A similar mechanism involving methylglyoxal-modification of other coregulator proteins may play a role in the pathobiology of a variety of conditions associated with changes in methylglyoxal concentration, including cancer and diabetic vascular disease.

Amino Acid Sequence↗

PubMed2006

Methylglyoxal comes of AGE.

The posttranslational modification of proteins by methylglyoxal, a highly reactive compound derived from glycolysis, may contribute to aging, diabetes, and other disorders. In this issue of Cell, Brownlee and colleagues (Yao et al., 2006) demonstrate a specific mechanism by which methylglyoxal modifies a transcriptional corepressor to enhance gene expression.

Aging↗

PubMed2004

Effect of methylglyoxal on intracellular calcium levels and viability in renal tubular cells.

Methylglyoxal (2-oxopropanal), a physiological glucose metabolite, is a highly reactive dicarbonyl compound that can induce stress in cells and cause apoptotic cell death. This study examines the early signaling effects of methylglyxal on renal cells. It was found that methylglyoxal caused a slow and sustained rise of intracellular Ca2+ concentration ([Ca2+]i) in a concentration-dependent manner (EC50=1.8 mM). Methylglyoxal also induced a [Ca2+]i rise when extracellular Ca2+ was removed, but the magnitude was reduced by 80%. Depletion of intracellular Ca2+ stores with thapsigargin (TG), an endoplasmic reticulum (ER) Ca2+ pump inhibitor, did not affect methylglyoxal's effect. In Ca2+-free medium, the methylglyoxal-induced [Ca2+]i rise was abolished by depleting stored Ca2+ with carbonylcyanide m-chlorophenylhydrazone (CCCP; a mitochondrial uncoupler). Methylglyoxal-caused [Ca2+]i rise in the Ca2+-containing medium was not affected by modulation of protein kinase C activity, presence of voltage-gated Ca2+ channel blockers, or preincubation with thiol-containing antioxidants. U73122, an inhibitor of phospholipase C, abolished ATP (but not methylglyoxal)-induced [Ca2+]i rise. Furthermore, the [Ca2+]i-elevating effect of methylglyoxal was cell type-dependent, because methylglyoxal failed to cause [Ca2+]i rises in CHO-K1, neutrophils, or platelets. Pretreatment with methylglyoxal for 0-24 h decreased cell viability in a concentration- and time-dependent manner. Meanwhile, methylglyoxal-induced cell death involved apoptotic and necrotic events, the former being the dominant. These findings suggest that methylglyoxal induced a significant rise in [Ca2+]i in Madin-Darby canine kidney (MDCK) renal tubular cells by stimulating both extracellular Ca2+ influx and CCCP-sensitive intracellular Ca2+ release via as yet unidentified mechanisms. The cell type-specific Ca2+ signaling may play an important role in the early process of cytotoxic action of methylglyoxal.

Animals↗

PubMed2006

Use of solid-phase microextraction to detect and quantify gas-phase dicarbonyls in indoor environments.

Solid-phase microextraction (SPME) was evaluated for the detection and quantification of the gas-phase dicarbonyls, glyoxal (GLY) and methylglyoxal (MGLY). Additionally, polydimethylsiloxane (PDMS), polydimethylsiloxane/divinylbenzene (PDMS/DVB), and carbowax/divinylbenzene (CW/DVB) fibers were tested to determine the optimum fiber for detection of these species. GLY and MGLY were derivatized with O-(2,3,4,5,6-pentafluorobenzyl)-hydroxylamine hydrochloride (PFBHA), extracted with SPME from headspace or bag chamber and then analyzed by GC/MS. The PDMS/DVB SPME fiber for on-fiber derivatization and subsequent sampling for gas-phase methylglyoxal provided the optimum combination of analytical reproducibility and sensitivity. Linearity of the calibration curve was achieved across a range of 11-222 microg/m(3) (4-75 ppb).

Air Pollutants↗

PubMed2004

Preparation and quantification of methylglyoxal in human plasma using reverse-phase high-performance liquid chromatography.

OBJECTIVES: To detect methylglyoxal (MG), a highly reactive alpha-oxoaldehyde found widespread throughout biological life, in human plasma using reverse-phase high-performance liquid chromatography method (RP HPLC) with UV detection. DESIGN AND METHODS: The processing of human plasma required protein precipitation with trifluoroacetic acid (TFA), incubation of the supernatant (2 h) with 1,2-diamino-4,5-dimethoxybenzene (DDB) to convert MG to 6,7-dimethoxy-2-methylquinoxaline (DMQ), freeze-drying, and RP HPLC analysis using 6,7-dimethoxy-2,3-dimethylquinoxaline (DMDQ) as an internal standard (IS). Simplified methods for the synthesis of MG and DDB are also described. RESULTS: Calibration curves were linear in the range of 200-1000 nM. The limit of detection was 30.6 and 45.9 pmol, at 215 and 352 nm, respectively. The intraday coefficients of variation were 6.9-12.6% for 215 nm and 3.5-12.6% for 352 nm. The interday coefficients of variation were 9.6-12.8% for 215 nm and 7.2-14.7% for 352 nm. Sample storage conditions together with statistical evaluation are also described. CONCLUSIONS: Here we present a rapid and inexpensive method for the determination of methylglyoxal in human plasma using RP HPLC with UV detection. The simplicity of the reported RP HPLC method makes it suitable for the detection of methylglyoxal in many human plasma samples.

Calibration↗

PubMed2005

Humoral methylglyoxal level reflects glycemic fluctuation.

OBJECTIVES: According to the nonenzymatic glycation hypothesis, excessive production of toxic alpha-oxoaldehydes is associated with diabetes tissue damage. The aim of this study was to examine the hypothesis that methylglyoxal overproduction is affected by glycemic fluctuation. DESIGN AND METHODS: Methylglyoxal was measured by HPLC in 41 patients with diabetes, and correlated with 9-point daily glucose profiles, fasting glucose level, as well as early (HbA1c) and advanced glycation products. The 24-h glycemia variability was expressed as the M value, a quantitative index of diurnal glucose fluctuation. RESULTS: Methylglyoxal was, in parallel, analyzed in the whole blood and the plasma of the same individual. Significantly higher concentrations were measured in plasma samples of both, patients with diabetes (n=41) (742+/-141 vs. 409+/-131 nmol/L; P=0.000001) and normoglycemic controls (n=10) (520+/-42 vs. 338+/-62 nmol/L; P=0.0002). Difference between plasma and whole blood methylglyoxal (DeltaMG) in the same individual showed higher DeltaMG values in patients with diabetes (346+/-165 vs. 167+/-86 nmol/L; P=0.0027). Elevated methylglyoxal production was observed in patients with M values>20, yielding a significant correlation between M values and methylglyoxal levels. A significant negative correlation between methylglyoxal and creatinine clearance was observed (r=-0.38, P=0.019). CONCLUSIONS: Methylglyoxal was demonstrated to be a parameter characterized by high sensitivity to glycemic fluctuation. The difference between plasma and whole blood concentrations, in the diabetic population versus control subjects might be associated with increased biogenesis, less efficient endogenous detoxification and/or decreased elimination.

Adolescent↗

PubMed2004

Enhanced degradation and decreased stability of eye lens alpha-crystallin upon methylglyoxal modification.

Methylglyoxal (MGO), a potent glycating agent, forms advanced glycation end products (AGEs) with proteins. Several diabetic complications including cataract are thought to be the result of accumulation of these protein-AGEs. alpha-Crystallin, molecular chaperone of the eye lens, plays an important role in maintaining the transparency of the lens by preventing the aggregation/inactivation of several proteins/enzymes in addition to its structural role. Binding of adenosine-5-triphosphate (ATP) to alpha-crystallin has been shown to enhance its chaperone-like function and protection against proteolytic degradation. In the earlier study, we have shown that modification of alpha-crystallin by MGO caused altered chaperone-like activity along with structural changes, cross-linking, coloration and subsequent insolubilization leading to scattering of light [Biochem. J. 379 (2004) 273]. In the present study, we have investigated ATP binding, stability and degradation of MGO-modified alpha-crystallin. Proteolytic digestion with trypsin and chymotrypsin showed that MGO-modified alpha-crystallin is more susceptible to degradation compared to native alpha-crystallin. Furthermore, ATP was able to protect native alpha-crystallin against proteolytic cleavage but not MGO-modified alpha-crystallin. Interestingly, binding studies indicate decreased ATP binding to MGO-modified alpha-crystallin and support the decreased protection by ATP against proteolysis. In addition, differential scanning calorimetric and denaturant-induced unfolding studies indicate that modification of alpha-crystallin by MGO leads to decreased stability. These results indicate that MGO-modification of alpha-crystallin causes partial unfolding and decreased stability leading to enhanced proteolysis. Cross-linking of these degraded products could result in aggregation and subsequent insolubilization as observed in senile and diabetic cataract lenses.

Adenosine Triphosphate↗

PubMed2006

Protein modification in aging: an update.

Post-translational modifications of proteins are an important biologic tool for the production of various protein species from a single gene, which may vary in conformation, function, biologic half-life and complex formation with other proteins. The present minireview summarizes a few selected research observations important for the role of post-translational modifications in biologic aging and age-related diseases, including farnesylation, methylglyoxal-derivatization, transglutaminase pathways and the formation of 3-nitrotyrosine and 2-oxo-histidine in vivo.

Aging↗

PubMed2005

The effects of partial thiamin deficiency and oxidative stress (i.e., glyoxal and methylglyoxal) on the levels of alpha-oxoaldehyde plasma protein adducts in Fischer 344 rats.

We hypothesized that in marginal thiamin deficiency intracellular alpha-oxoaldehydes form macromolecular adducts that could possibly be genotoxic in colon cells; and that in the presence of oxidative stress these effects are augmented because of decreased detoxification of these aldehydes. We have demonstrated that reduced dietary thiamin in F344 rats decreased transketolase activity and increased alpha-oxoaldehyde adduct levels. The methylglyoxal protein adduct level was not affected by oral glyoxal or methylglyoxal in the animals receiving thiamin at the control levels but was markedly increased in the animals on a thiamin-reduced diet. These observations are consistent with our suggestion that the induction of aberrant crypt foci with marginally thiamin-deficient diets may be a consequence of the formation of methylglyoxal adducts.

Aldehydes↗

PubMed2005

Transgenic tobacco plants overexpressing glyoxalase enzymes resist an increase in methylglyoxal and maintain higher reduced glutathione levels under salinity stress.

The mechanism behind enhanced salt tolerance conferred by the overexpression of glyoxalase pathway enzymes was studied in transgenic vis-à-vis wild-type (WT) plants. We have recently documented that salinity stress induces higher level accumulation of methylglyoxal (MG), a potent cytotoxin and primary substrate for glyoxalase pathway, in various plant species [Yadav, S.K., Singla-Pareek, S.L., Ray, M., Reddy, M.K. and Sopory, S.K. (2005) MG levels in plants under salinity stress are dependent on glyoxalase I and glutathione. Biochem. Biophys. Res. Commun. 337, 61-67]. The transgenic tobacco plants overexpressing glyoxalase pathway enzymes, resist an increase in the level of MG that increased to over 70% in WT plants under salinity stress. These plants showed enhanced basal activity of various glutathione related antioxidative enzymes that increased further upon salinity stress. These plants suffered minimal salinity stress induced oxidative damage measured in terms of the lipid peroxidation. The reduced glutathione (GSH) content was high in these transgenic plants and also maintained a higher reduced to oxidized glutathione (GSH:GSSG) ratio under salinity. Manipulation of glutathione ratio by exogenous application of GSSG retarded the growth of non-transgenic plants whereas transgenic plants sustained their growth. These results suggest that resisting an increase in MG together with maintaining higher reduced glutathione levels can be efficiently achieved by the overexpression of glyoxalase pathway enzymes towards developing salinity stress tolerant plants.

Antioxidants↗

PubMed2006

Heat-shock protein 27 is a major methylglyoxal-modified protein in endothelial cells.

In endothelial cells cultured under high glucose conditions, methylglyoxal is the major intracellular precursor in the formation of advanced glycation endproducts. We found that endothelial cells incubated with 30 mM d-glucose produced approximately 2-fold higher levels of methylglyoxal but not 3-deoxyglucosone and glyoxal, as compared to 5 mM d-glucose. Under hyperglycaemic conditions, the methylglyoxal-arginine adduct argpyrimidine as detected with a specific antibody, but not N(e)-(carboxymethyl)lysine and N(e)-(carboxyethyl)lysine, was significantly elevated. The glyoxylase I inhibitor HCCG and the PPARgamma ligand troglitazone also increased argpyrimidine levels. Increased levels of argpyrimidine by glucose, HCCG and troglitazone are accompanied by a decrease in proliferation of endothelial cells. A 27 kDa protein was detected as a major argpyrimidine-modified protein. With in-gel digestion and mass spectrometric analysis, we identified this major protein as heat-shock protein 27 (Hsp27). This argpyrimidine modification of Hsp27 may contribute to changes in endothelial cell function associated to diabetes.

Cells, Cultured↗

PubMed2005

Diagnosis of cell death induced by methylglyoxal, a metabolite derived from glycolysis, in Saccharomyces cerevisiae.

Methylglyoxal (MG) is a ubiquitous metabolite derived from glycolysis; however, this aldehyde kills all types of cell. We analyzed the properties of MG-induced cell death of the budding yeast Saccharomyces cerevisiae. The MCA1 gene encodes a caspase homologue that is involved in H2O2-induced apoptosis in yeast, although the disruption of MCA1 did not repress sensitivity to MG. In addition, the intracellular oxidation level did not increase under conditions in which MG kills the cell. Furthermore, the disruption of genes encoding antioxidant enzymes did not affect the susceptibility to MG. Here, we demonstrate that yeast cells killed by MG do not exhibit the characteristics of apoptosis in a TUNEL assay or an annexin V staining, but show those of necrosis upon propidium iodide staining. We demonstrate that MG at high concentrations provokes necrotic cell death without the generation of reactive oxygen species in S. cerevisiae.

Cell Death↗

PubMed2004

Yeast cells display a regulatory mechanism in response to methylglyoxal.

Methylglyoxal (MG), a glycolytic by-product, is an extremely toxic compound. This fact suggests that its synthesis and degradation should be tightly controlled. However, little is known about the mechanisms that protect yeast cells against MG toxicity. Here, we show that in Saccharomyces cerevisiae, MG exposure increased the internal MG content and activated the expression of GLO1 and GRE3, two genes involved in MG detoxification; GPD1, the gene for glycerol synthesis; and TPS1 and TPS2, the trehalose pathway genes. This response was specific as demonstrated by the analysis of marker genes and effectors of the general stress response. Physiological experiments with MG-treated cells showed that this compound triggers the overproduction of glycerol. Furthermore, a gpd1 gpd2 double mutant showed enhanced MG contents compared with the wild-type. Overall, these results appeared to indicate that up-variations in the intracellular content of the toxic compound are perceived by the cell as a primary signal to trigger the transcriptional response. In agreement with this, MG-instigated GPD1 activation was enhanced in strains lacking GLO1, and this effect correlated with the internal MG content. Finally, induction of GPD1, TPS1 and GRE3, and enhanced MG contents were also observed in low-glucose-growing cells subjected to a sudden increase in glucose availability. The implications of this regulatory mechanism on protection against MG are discussed.

Culture Media↗

PubMed2005

Methylglyoxal-induced nitric oxide and peroxynitrite production in vascular smooth muscle cells.

Methylglyoxal (MG) is a metabolite of glucose. Our previous study demonstrated an elevated MG level with an increased oxidative stress in vascular smooth muscle cells (VSMCs) from spontaneously hypertensive rats. Whether MG causes the generation of nitric oxide (NO) and superoxide anion (O2*-), leading to peroxynitrite (ONOO-) formation in VSMCs, was investigated in the present study. Cultured rat thoracic aortic SMCs (A-10) were treated with MG or other different agents. Oxidized DCF, reflecting H2O2 and ONOO- production, was significantly increased in a concentration- and time-dependent manner after the treatment of SMCs with MG (3-300 microM) for 45 min-18 h (n = 12). MG-increased oxidized DCF was effectively blocked by reduced glutathione or N-acetyl-l-cysteine, as well as L-NAME (p < 0.05, n = 12). Both O2*- scavenger SOD and NAD(P)H oxidase inhibitor DPI significantly decreased MG-induced oxidized DCF formation. MG significantly and concentration-dependently increased NO and O2*- generation in A-10 cells, which was significantly inhibited by L-NAME and SOD or DPI, respectively. In conclusion, MG induces significant generation of NO and O2*- in rat VSMCs, which in turn causes ONOO- formation. An elevated MG level and the consequential ROS/RNS generation would alter cellular signaling pathways, contributing to the development of different insulin resistance states such as diabetes or hypertension.

Animals↗

PubMed2005

Carbonyl stress and NMDA receptor activation contribute to methylglyoxal neurotoxicity.

Methylglyoxal (MG) is a reactive alpha-ketoaldehyde physiologically generated as a by-product of glycolysis. MG that is able to form protein adducts resulting in advanced glycation end products accumulates under conditions associated with neurodegeneration such as impaired glucose metabolism or oxidative stress. In the present study, short-term exposure of human neuroblastoma SH-SY5Y cells to MG was associated with an early depolarization of the plasma membrane, glutamate release, and formation of reactive oxygen species. In addition, long-term exposure (24 h) of SH-SY5Y cells to MG caused a decrease in cell viability, intracellular ATP, and rhodamine 123 (Rh-123) fluorescence. ATP depletion and the decrease in Rh-123 fluorescence were prevented by carbonyl scavengers, the nitric oxide synthase inhibitor L-NAME, and N-methyl-d-aspartate (NMDA) receptor antagonists. Furthermore, the MG-induced glutamate release and the loss in cell viability were prevented by NMDA receptor antagonists. Therefore, MG renders cells more vulnerable to excitotoxicity. In conclusion, carbonyl scavengers as well as NMDA receptor antagonists may represent effective therapeutic tools to reduce the risk of pathophysiological changes associated with carbonyl stress in neurodegenerative diseases.

Adenosine Triphosphate↗

PubMed2005

A novel HPLC procedure for detection and quantification of aminoacetone, a precursor of methylglyoxal, in biological samples.

Increase in methylglyoxal is thought to be involved in different pathological conditions. Deamination of aminoacetone by semicarbazide-sensitive amine oxidase (SSAO) leads to production of methylglyoxal. We have synthesized aminoacetone and developed a novel HPLC procedure for its quantitative determination. The urinary excretion of aminoacetone is approximately 20-30 microg/mouse/day, and the concentration is about 0.5 microg/g in mouse liver and small intestine. SSAO inhibitor increases aminoacetone levels in both tissues and urines. Results confirm that aminoacetone is an endogenous substrate for SSAO. However, data also indicate that deamination is not the only catabolic pathway for aminoacetone.

Acetone↗

PubMedDate not supplied

A copper chelating agent suppresses carbonyl stress in diabetic rat lenses.

To clarify whether transition metals are involved in carbonyl stress in diabetic tissues, we observed the effects of a metal chelating agent, trientine (TE) hydrochloride on the levels of methylglyoxal (MG), 3-deoxyglucosone (3-DG), advanced glycation end products, 8-hydroxy-2'-deoxyguanosine (8-OHdG), and polyol pathway metabolites along with semicarbazide-sensitive amine oxidase (SSAO) enzyme activity in lenses from streptozotocin-induced diabetic rats. Lens MG and 3-DG levels were significantly higher in diabetic rats than nondiabetic controls, and TE significantly restored the increase of these compounds. Lens argpyrimidine was also increased in diabetic rats as compared with controls and was significantly reduced by TE. Lens SSAO activity and 8-OHdG were also significantly elevated in diabetic rats, and TE suppressed both of them, whereas TE showed no effect on the polyol pathway metabolites. The results indicate that transition metals play a significant role in the formation of MG and 3-DG via oxidative stress and SSAO activity.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed2004

Processing of protein glycation, oxidation and nitrosation adducts in the liver and the effect of cirrhosis.

BACKGROUND/AIMS: Plasma proteins are modified non-enzymatically in vivo by glycation, oxidation and nitrosation processes. Hepatic extraction of albumin glycated in vitro was reported but it is not clear if plasma proteins glycated in vivo also undergo hepatic extraction. We investigated the hepatic extraction of glycated, oxidised and nitrosated proteins in vivo. METHODS: Protein glycation, oxidation and nitrosation marker residues and free adducts were determined in portal, hepatic and peripheral venous blood plasma of cirrhotic patients and hepatic and peripheral venous blood plasma (as a surrogate of portal venous blood) of control subjects by liquid chromatography-mass spectrometry. RESULTS: There was no evidence for extraction of glycated, oxidised or nitrosated proteins or related free adducts by the liver in control subjects. There was limited extraction of methylglyoxal-modified proteins in cirrhotic patients and twofold increases in the concentrations of fructosyl-lysine and advanced glycation endproduct residues of plasma protein, with respect to controls. Remarkably, glyoxal-derived hydroimidazolone free adduct was increased 14-16-fold probably as a consequence of hepatic lipid peroxidation. CONCLUSIONS: We found no evidence for hepatic extraction of glycated, oxidised and nitrosated proteins or related free adducts in subjects with normal liver function and limited extraction of methylglyoxal-modified protein in cirrhotic subjects.

Adult↗