lactoylglutathione lyase

..Since hyperglycemia-induced reactive oxygen species (ROS) activate many pathways of diabetic tissue damage, the effect of these ROS on RAGE and RAGE ligand expression was evaluated...

..Thereby, we identified a novel molecular mechanism for anxiety-related behavior in mice that may help to elucidate genesis of psychiatric disorders in humans...

..Together, our data demonstrate the potential of transcriptomics applied to animal models of human diseases. They suggest a previously unidentified role for glyoxalase I in neurodegenerative disease...

..Inhibitors of glyoxalases are considered as anti-inflammatory and anti-carcinogenic agents. The recent finding that various polyphenols modulate Glo1 activity has prompted us to assess curcumin's potency as an Glo1 inhibitor...

..This leads to an anionic complex, which is consistent with an observed 1.7 eV decrease in the Ni K-edge energy. Plausible reaction mechanisms for Ni-GlxI are discussed in light of the structural information available...

..Finally, a preliminary evaluation of the efficacy of selected GlxI inhibitors in tumour-bearing mice is given...

..In conclusion, the decrease of glyoxalase I expression with increasing AD stage might be one reason for methylglyoxal-induced neuronal impairment, apoptosis, and AGE formation in plaques and tangles...

..Regulatory mechanisms of AGE formation in vivo remain an issue of particular interest. We investigated a role of the glyoxalase detoxification system of precursor reactive carbonyl compounds (RCOs) in the in vivo AGE formation...

..In summary, these data suggest that the TNF-induced phosphorylation of GLO1 is the dominant factor for cell death...

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..In this study, we quantitatively measured GLO1 enzyme activity in various human solid tumor cells, and the antiproliferative effect of the GLO1 inhibitor was examined...

..The possible causes for the discrepancy between data obtained from initial rate analysis and progress curve analysis, for glyoxalase II, are discussed...

..These data emphasize the pivotal role of antioxidant and detoxifying systems in determining the grade of sensitivity of cells to methylglyoxal...

..We did not observe significant linkage or association between any SNP and ASDs. Therefore, we suggest that common variants in GLO1 are not significant susceptibility factors for ASDs in the Finnish population...

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..Molecular biological experiments suggest that inhibition of GLO1 enzyme activity is related to the clinically recognized beneficial side effects of the indomethacin family of nonsteroidal antiinflammatory drugs...

..2 microM. Our results show that the glyoxalase pathway is the main detoxification pathway for 2-oxoaldehydes in yeast, and is likely to be the key enzymatic anti-glycation agent in these cells...

..These findings establish the potential of manipulation of the glyoxalase pathway for increased salinity tolerance without affecting yield in crop plants...

..Glyoxalase I has a critical role in the prevention of glycation reactions mediated by methylglyoxal, glyoxal and other alpha-oxoaldehydes in vivo...

..may contribute to pericyte death by apoptosis during the early stages of diabetic retinopathy...

..It countered drug resistance and was a potent antitumour agent against lung and prostate carcinoma. Glyoxalase I overexpression was also found in invasive ovarian cancer and breast cancer...

..While our data suggest that this polymorphism is unlikely to have a major function in the pathogenesis of panic disorder, it could play a role in the subgroup of patients without agoraphobic avoidance...

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..The presence of both protein markers in red or white blood cells, respectively, creates the opportunity to screen for their expression in clinical blood specimens from patients suffering from anxiety...

..Thus, an underappreciated metabolic pathway involving fatty acid beta-oxidation also regulates theta oscillations during sleep...

..The contrasting substrate specificities of human and trypanosomatid glyoxalase enzymes, confirmed in the present study, suggest that the glyoxalase system may be an attractive target for anti-trypanosomal chemotherapy...

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..Western blot analysis has also shown accumulation of advanced glycation end products (AGE's) in autism brains. These data suggest that homozygosity for A419 GLO1 resulting in Glu111 is a predisposing factor in the etiology of autism...

..The kinetic properties of recombinant glyoxalase I were indistinguishable from those of the enzyme purified from human tissues...

..This expression pattern was not appreciably altered by salt-stress. We suggest that the increased expression of glyoxalase-I may be linked to a higher demand for ATP generation and to enhanced glycolysis in salt-stressed plants...

..Examination of colon carcinomas for the amplification of the glyoxalase-I gene by Southern blot analysis revealed no change in gene copy number. These results suggest induction of the glyoxalase-I gene expression in colon carcinomas...

..Latest research suggests there are functional modifications of this process--implying a role in cell signalling, ageing and disease...

..Hyperserotoninemia, macrocephaly, and peptiduria represent some of the best-characterized endophenotypes in autism research...

..This study aimed to replicate the genetic association of the C419A of the GLO1 gene with autism and to perform mutation screening of all the exons of the GLO1 gene in a sample of Han Chinese patients with autism from Taiwan...

..This structural family appears to allow members to form with or without domain swapping...

..These findings suggest that phosphorylation and NO-modification of glyoxalase I provides another control mechanism for modulating the basal and TNF-induced expression of NF-kappaB-responsive genes...

..Glyoxalase I is a metalloenzyme of the glyoxalase pathway that plays a central role in eliminating the toxic metabolite methyglyoxal. The protozoan parasite Leishmania donovani possesses a unique trypanothione dependent glyoxalase system...

..Additional studies will examine whether glyoxalase-I has an impact beyond that of a biomarker to predict the genetic predisposition to anxiety- and depression-like behavior...

..These results suggest that the aberrant expression of Glo1 might be involved in the pathophysiology of mood disorders...

..A comparison of the human and E. coli enzymes suggests that there are differences between the active sites that might be exploited for therapeutic use...

..Taken together, these results indicate that GLO1 is a resistant factor to antitumor agent-induced apoptosis in human leukemia cells and that the GLO1 inhibitor could be a drug resistance-reversing agent...

..elegans lifespan. In contrast, knock-down of CeGly increases MG modifications of mitochondrial proteins and mitochondrial ROS production, and decreases C. elegans lifespan...

..3 A from the metal and is in an ideal position for reprotonation of the transition state intermediate. In contrast, Glu 172 is directly coordinated to the zinc ion in the complexes with S-benzylglutathione and with NBC-GSH...

..The effects of pH on the kinetics of the nickel-activated enzyme were also studied. This is the first example of a non-zinc activated GlxI whose maximal activation is seen with Ni2+...

..The importance of the glyoxalase pathway as a therapeutic target is very small, compared to the much greater effects caused by decreasing trypanothione concentration or increasing methylglyoxal concentration...

..These data suggest that the glutathione-dependent glyoxalase I is the dominant detoxification pathway for MG in E. coli and that the product of glyoxalase I activity, S-lactoylglutathione, is the activator of KefB and KefC...

..This trypanothione-dependent glyoxalase I is therefore an attractive focus for additional biochemical and genetic investigation as a possible target for rational drug design...

..Several features of the Glo-1 polymorphism in the mouse recommend it as a marker of choice for the H-2 region...

..With respect to sequence alignments, these inserts may potentially contribute to defining the metal specificity of GlxI at a structural level...

..These results support the hypothesis of domain-swapping and subunit fusion as mechanisms in glyoxalase I evolution...

..Both of these genes are involved in oxidative stress metabolism, linking this pathway with anxiety-related behaviour...

..Difference in the substrate specificity of the human and LDGLOI enzyme could be exploited for structure-based drug designing of selective inhibitors against the parasite...

..mutans. Proteome analysis of S. mutans demonstrated that lactoylglutathione lyase (LGL) was up-regulated during acid challenge...

..These results provide a basis for the rational design of new therapeutics to normalize impaired ischemia-induced vasculogenesis in patients with diabetes...

..Here, we show a crossing link between glyoxalases and the immune system. The results described herein introduce glyoxalases as a possible target for therapeutic approaches of immune suppression...

..The remarkable access to mechanism space that is provided by the VOC superfamily appears to derive from a simple, pseudosymmetric structural fold that maximizes the catalytic versatility of the metal center...

..These differences correlate with the differential binding of glutathione and trypanothione-based substrates, and thus offer a route to the rational design of L. major-specific GLO1 inhibitors...

..There are two NADP-dependent 2-ODHs in human liver. Both of these require an activating amine. The physiological activator is unknown...

..Recent studies on the Pseudomonas aeruginosa genome have led to the characterization of three different glyoxalase I enzymes, two of which follow a Ni2+/Co2+ activation profile and the third exhibits a human-like preference for Zn2+...

..In this paper we review work on plant glyoxalases especially with respect to their role under abiotic stresses...

..The degradation of D-lactate, an end product of the methylglyoxal bypass, into acetaldehyde and formate was suggested as a possible way to explain the results...

..Our findings suggest that glyoxalase I is upregulated in AD in a compensatory manner to maintain physiological methylglyoxal and glyoxal levels...

..Knowledge regarding the regulation of glyoxalases by testosterone may provide insights into the importance of these enzymes in human prostate carcinomas in vivo...

..The purpose of this study was to investigate the behaviour of Saccharomyces cerevisiae in response to extracellular methylglyoxal...

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..Furthermore, they extend the current knowledge on allosteric regulation of monomeric proteins in general...

..CONCLUSION: Our results suggest that PM can inhibit AGE formation in the diabetic lens by enhancing the activity of aldose reductase and reacting with precursors of AGEs...

..This, in turn, triggers widespread apoptotic cell death, occurring through the convergence of both mitochondrial and Fas-receptor pathways...

..In summary, our data suggest that a reduced glyoxalase I activity mimics some changes associated with neurodegeneration, such as neurite retraction and apoptotic cell death...

..This argpyrimidine modification of Hsp27 may contribute to changes in endothelial cell function associated to diabetes...

..falciparum Glo inhibitors were active in the lower nanomolar range. The Glo system of Plasmodium will be further evaluated as a target for the development of antimalarial drugs...

..Total glutathione content, catalase, and glutathione peroxidase activities, were related with the highest metal concentrations in L. crystallinus from Lake Piediluco...

..Indeed, the production of this compound should be lower in FR animals as compared to AL fed ones, due to the lower level serum glucose concentration during the life span of the former with respect to the latter group...

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..Our studies show that pyridoxamine reduces oxidative stress and AGE formation. We suspect that a direct interaction of pyridoxamine with MG partly accounts for AGE inhibition...

..GII activity remains unchanged or increases (liver extract, 0.5 ppm of Cu), maybe to safeguard enough cellular levels of GSH...

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..The clinical relevance of this approach is yet to be documented...

..100% of the resting cell concentration during the initial 10 min of the activation period. The presence of S-D-lactoylglutathione in neutrophils may be related to its ability to stimulate microtubule assembly...

..Both enzymes help in the detoxification of cigarette smoke induced chemicals and biochemicals...

..This inhibition of the glyoxalase system could contribute to troglitazone's hepatotoxic action which has previously been reported in a small percentage of individuals...

..Methylglyoxal resistance appeared to be due to the simultaneous increase in the activities of these two enzyme systems...

..5) As for enzyme, activities of glyoxalase I and II became markedly decreased with age in livers, whereas the activity of glyoxalase I in muscle was maintained at control level and glyoxalase II increased with age...

..Moreover, the defensive glyoxalase III is also inactivated by the oxidative stress imposed by the lack of SOD, thereby exacerbating the deleterious effect of sugar oxidation...

..We conclude that exogenous GLD enhances MG and MG-AGE levels in the rat lens and that this increase is accompanied by a loss in GSH. In addition, inhibition of glyoxalase I promotes MG accumulation...

..The differential effect of creatine on mitochondria of cardiac and malignant cells has been discussed with reference to the therapeutic potential of methylglyoxal...

..Moreover, we show that nucleocytoplasmic localization of Yap1 closely correlates with growth phase and intracellular MG level. We propose a novel regulatory pathway underlying Yap1 activation by a natural metabolite in the cell...

..This is the first report describing the characterisation of a glyoxalase I from a pathogen of any description. The gene has been sequenced, functionally characterised and shown not to be required for the infection of wheat by S. nodorum...

..The increased derangement of MG metabolism and associated glycation, oxidative and nitrosative stress in the propositus may be linked to neurodegenerative process in triosephosphate isomerase deficiency...

..The strongest inhibitors of this antitumor target enzyme likely bind simultaneously to the active site on each subunit to give K(i) values as small as 0.96 nM (n = 6). [structure: see text]..

..It thus appears that glyoxalase III is regulated by rpoS and might be important for survival of non-growing E. coli cultures...

..Both pyruvate and L-lactate levels increased in the liver and plasma of MDAB-fed rats when rats had obvious symptoms of hepatoma...

..That way MG play a role in the events of the development of diabetic complications...

..Such insights may hint to novel, non-classical pathways that necessitate further investigations...

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..lactate dehydrogenase, fructose bisphosphate aldolase, acetoin reductase, superoxide dismutase, and lactoylglutathione lyase. Proteins down-regulated at pH 5...

..Some of the affinity labels are designed to be hydrolyzed by GlxII, an enzyme activity that is high in normal cells but low in tumor cells. ..

..It provides a testable model that connects hyperglycemia-> oxidative stress-> growth factors-> diabetic retinopathy. ..

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..5) 3-OH Isobutyryl CoA hydrolase (HIBCH) catalyzes hydrolysis of a thioester in valine catabolism. We will study HIBCH so that we can determine whether the reaction proceeds via and enolate anion or an anionic tetrahedral intermediate. ..

..The bacterium typically colonizes the human intestine shortly after birth where it remains the predominant facultative microorganism. Understanding the biochemistry of E. coli is fundamental to understanding its pathogenesis. ..

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..Dr. Gerlt and his group will investigate the mechanism of this reaction so that they can better understand the underlying catalytic strategy used by the members of the superfamily. ..

..abstract_text> ..

..The intent of this investigation is to establish the mechanistic and structural bases for the design of drugs to counter both plasmid borne and genomically encoded resistance to fosfomycin. ..

..4) We will test a structural blueprint for functional diversity in the (beta/alpha)7beta-barrel fold by determining whether new functions can be generated by in vitro evolution. ..

..4) A structural blueprint for functional diversity in the ((beta/alpha)8-barrel fold will be tested. ..

..The intent of this investigation is to establish the mechanistic and structural bases for the design of drugs to counter both plasmid borne and genomically encoded resistance to fosfomycin. ..

..Since methylglyoxal is toxic to cells and must be removed by an active glyoxalse system, inhibition of a MSH based system could result in a treatment for many mycobacterial-based diseases such as tuberculosis. ..

..The bacterium typically colonizes the human intestine shortly after birth where it remains the predominant facultative microorganism. Understanding the biochemistry of E. coli is fundamental to understanding its pathogenesis. ..

..abstract_text> ..

..The bacterium typically colonizes the human intestine shortly after birth where it remains the predominant facultative microorganism. Understanding the biochemistry of E. coli is fundamental to understanding its pathogenesis. ..

..The project is a response to program announcement PA-97-026, Aspergillosis, Ehrlichioses and Drug Resistance. ..

..The kinetic demonstration of forms specific for citrate and for cis-aconitate may lead others to study the nature of the changes in conformation required for the reaction and the recycling process. ..

..groups will allow for the rational development of novel strategies to restore normal compensatory vasculogenesis in diabetes, thus preventing the poor outcome of cardiovascular events (Ml, stroke, amputation) associated with the disease ..

..Peptide mapping, sequencing, and fast-atom bombardment mass spectroscopy will be used to analyze peptide and carbohydrate of intracellularly glycated bFGF...

..Supershift experiments will use commercially availableantibodies. IP-westernsof cell extracts will be immunoblotted with antibodies to glyoxalase I-substrate-derived advanced glycationendproducts. ..

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..Supershift experiments will use commercially available antibodies. IP-westerns of cell extracts will be immunoblotted with antibodies to glyoxalase I-substrate- derived advanced glycation endproducts. ..