Disease relevance of methylglyoxal

• 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 [1].
• Cytotoxicity of methylglyoxal bis(guanylhydrazone) in combination with alpha-difluoromethylornithine against HeLa cells and mouse L1210 leukemia [2].
• We recently demonstrated in isolated, perfused hearts that radiolabeled pyruvaldehyde bis(N4-methylthiosemicarbazonato)copper(II) (Cu-PTSM) is well extracted throughout a range of conditions including ischemia, hypoxia, and hyperemia [3].
• The inhibition by methylglyoxal bis(guanylhydrazone) of the induction of thymidine kinase by adenovirus type 5 is probably unrelated to its effects on polyamine biosynthesis [4].
• Effects of alpha-difluoromethylornithine and methylglyoxal bis(guanylhydrazone) on the growth of experimental renal adenocarcinoma in mice [5].

Psychiatry related information on methylglyoxal

• Methylglyoxal, glyoxal, and their detoxification in Alzheimer's disease [6].

High impact information on methylglyoxal

• Methylglyoxal modification of mSin3A links glycolysis to angiopoietin-2 transcription [7].
• Methylglyoxal modification of mSin3A links glycolysis to angiopoietin-2 transcription [1].
• The posttranslational modification of proteins by methylglyoxal, a highly reactive compound derived from glycolysis, may contribute to aging, diabetes, and other disorders [8].
• 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 [8].
• Methylglyoxal (MG), a dicarbonyl compound produced by the fragmentation of triose phosphates, forms advanced glycation endproducts (AGEs) in vitro [9].

Chemical compound and disease context of methylglyoxal

• One of the mechanisms protecting eukaryotic cells against its toxicity is the glyoxalase system, composed of glyoxalase I and II (glo1 and glo2), which converts methylglyoxal into d-lactic acid in the presence of glutathione [10].
• Furthermore, the DHA toxicity was not linked to the presence of oxygen or to the known harmful agents methylglyoxal and formaldehyde [11].
• Methylglyoxal synthetase, which catalyzes the conversion of dihydroxyacetone phosphate to methylglyoxal and inorganic phosphate, has been isolated and crystalized in good yields from Proteus vulgaris [12].
• Reduction of trioses by NADPH-dependent aldo-keto reductases. Aldose reductase, methylglyoxal, and diabetic complications [13].
• Escherichia coli possesses two glutathione-gated potassium channels, KefB and KefC, that are activated by glutathione-S-conjugates formed with methylglyoxal [14].

Biological context of methylglyoxal

• Tumor necrosis factor-induced modulation of glyoxalase I activities through phosphorylation by PKA results in cell death and is accompanied by the formation of a specific methylglyoxal-derived AGE [15].
• As few as one or two "hits" with methylglyoxal per protein molecule have previously been reported to be sufficient to cause protein endocytosis and subsequent degradation [16].
• HAGH functions in a pathway to detoxify methylglyoxal, a compound present in coffee and alcoholic beverages and produced as a by-product of oxidative stress [17].
• The generality of methylglyoxal bis(guanylhydrazone)-induced mitochondrial damage and the dependence of this effect on cell proliferation [18].
• Likewise, we showed that cells deficient in GLX2 are hypersensitive to methylglyoxal-induced apoptosis [19].

Anatomical context of methylglyoxal

• Several artifacts were considered before concluding that the methylglyoxal was associated with cellular structures, including phosphate elimination from triose phosphates, carbohydrate degradation under the assay conditions, and interference from the derivatizing agent used as part of the assay procedure [16].
• Methylglyoxal bis(guanylhydrazone) completely inhibits the induction of thymidine kinase after serum stimulation of quiescent fibroblasts only if added within 3 h after serum, whereas calcium deprivation blocks this induction up to 12 h after serum stimulation [20].
• Rhodamine 123 exhibited anticarcinoma activity in mice and this activity was potentiated by 2-deoxyglucose and methylglyoxal bis(guanylhydrazone), a chemotherapeutic agent that is toxic to mitochondria [21].
• Comparison of specificity of inhibition of polyamine synthesis in bovine lymphocytes by ethylglyoxal bis(guanylhydrazone) and methylglyoxal bis(guanylhydrazone) [22].
• Three independent variants (G2, G4, G5), resistant to methylglyoxal bis(guanylhydrazone), an anticancer drug, have been isolated by single step selection from an adenovirus-transformed rat brain cell line (1) [23].

Associations of methylglyoxal with other chemical compounds

• The zinc metalloenzyme glyoxalase I catalyses the glutathione-dependent inactivation of toxic methylglyoxal [24].
• While methylglyoxal bis(guanylhydrazone) demonstrates pronounced cytotoxicity at moderate extracellular concentrations, DFMO is tolerated well by this cell line at concentrations of up to 10 mM, as assayed by clonogenic survival after treatments at 37 degrees [25].
• Modification of uptake and antiproliferative effect of methylglyoxal bis(guanylhydrazone) by treatment with alpha-difluoromethylornithine in rodent cell lines with different sensitivities to methylglyoxal bis(guanylhydrazone) [26].
• Cross-sectional measures of methylglyoxal production by red blood cells incubated in 30 mmol/l glucose were increased in nephropathy progressors relative to nonprogressors in the ONPN (P = 0.027) and also reflected 5-year GBM thickening in the NHS cohort (P = 0.04) [27].
• Whole embryo culture was used to investigate a possible association of hyperglycemia-induced disturbances of embryo development with tissue levels of the three alpha-oxoaldehydes: glyoxal, methylglyoxal, and 3-deoxyglucosone (3-DG) [28].

Gene context of methylglyoxal

• We found that glyoxalase I (GLO1), an enzyme that detoxifies methylglyoxal, is selectively overexpressed in the apoptosis-resistant UK711 cells [29].
• Glyoxalase I activity increased approximately 95-fold when the GLO1 gene was introduced into the yeast cell with a multicopy plasmid, and the resultant transformant showed the increased resistance against methylglyoxal [30].
• Aminoguanidine, an inhibitor of AGE formation, partially prevented the EGFR dysfunction induced by GO and MGO [31].
• Phorbol 12-myristate 13-acetate protects Jurkat cells from methylglyoxal-induced apoptosis by preventing c-Jun N-terminal kinase-mediated leakage of cytochrome c in an extracellular signal-regulated kinase-dependent manner [32].
• This is the first report of the effects of a sulphonylnitromethane on either human aldose reductase or utilization of methylglyoxal [33].
• Methylglyoxal modification of mSin3A results in increased recruitment of O-GlcNAc-transferase, with consequent increased modification of Sp3 by O-linked N-acetylglucosamine [34].

Analytical, diagnostic and therapeutic context of methylglyoxal

• However, analysis by isoelectric focusing indicates two major bands (pI 4.7 and 4.9) that stain as glycoproteins as well as for H2O2-producing activity in the presence of methylglyoxal [35].
• Serum 24-h urine and skin samples were monitored for N(epsilon)-carboxymethyl-lysine and methylglyoxal derivatives by enzyme-linked immunosorbent assays [36].
• Peptide mapping identifies hotspot site of modification in human serum albumin by methylglyoxal involved in ligand binding and esterase activity [37].
• Formation of methylglyoxal was confirmed by colorimetric and enzymatic estimations as well as by paper chromatography and its spectrum [38].
• The antiproliferative activity of methylglyoxal has been investigated for pharmacological application in cancer chemotherapy [39].

References