lactoylglutathione lyase

Summary

Summary: An enzyme that catalyzes the interconversion of methylglyoxal and lactate, with glutathione serving as a coenzyme. EC 4.4.1.5.

Top Publications

  1. pmc Curcumin inhibits glyoxalase 1: a possible link to its anti-inflammatory and anti-tumor activity
    Thore Santel
    Institute of Biochemistry, University of Leipzig, Leipzig, Germany
    PLoS ONE 3:e3508. 2008
  2. pmc Hyperglycemia-induced reactive oxygen species increase expression of the receptor for advanced glycation end products (RAGE) and RAGE ligands
    Dachun Yao
    Department of Medicine, Diabetes Research Center, Albert Einstein College of Medicine, Bronx, New York, USA
    Diabetes 59:249-55. 2010
  3. ncbi Glyoxalase I--structure, function and a critical role in the enzymatic defence against glycation
    P J Thornalley
    Department of Biological Sciences, University of Essex, Central Campus, Wivenhoe Park, Colchester, Essex CO4 3SQ, U K
    Biochem Soc Trans 31:1343-8. 2003
  4. pmc Protein and nucleotide damage by glyoxal and methylglyoxal in physiological systems--role in ageing and disease
    Paul J Thornalley
    Protein Damage and Systems Biology Research Group, Clinical Sciences Research Institute, Warwick Medical School, University of Warwick, University Hospital, Coventry, UK
    Drug Metabol Drug Interact 23:125-50. 2008
  5. ncbi Glyoxalase in tumourigenesis and multidrug resistance
    Paul J Thornalley
    Clinical Sciences Research Institute, Warwick Medical School, University of Warwick, University Hospital, Coventry, UK
    Semin Cell Dev Biol 22:318-25. 2011
  6. pmc The glyoxalase system: new developments towards functional characterization of a metabolic pathway fundamental to biological life
    P J Thornalley
    Department of Chemistry and Biological Chemistry, University of Essex, Colchester, U K
    Biochem J 269:1-11. 1990
  7. pmc Glyoxalase 1 increases anxiety by reducing GABAA receptor agonist methylglyoxal
    Margaret G Distler
    Department of Pathology, University of Chicago, Chicago, Illinois 60637, USA
    J Clin Invest 122:2306-15. 2012
  8. pmc The critical role of S-lactoylglutathione formation during methylglyoxal detoxification in Escherichia coli
    Ertan Ozyamak
    School of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK
    Mol Microbiol 78:1577-90. 2010
  9. ncbi Molecular enzymology of the glyoxalase system
    Bengt Mannervik
    Department of Biochemistry and Organic Chemistry, Uppsala University, Biomedical Center, Uppsala, Sweden
    Drug Metabol Drug Interact 23:13-27. 2008
  10. ncbi Transcriptional control of glyoxalase 1 by Nrf2 provides a stress-responsive defence against dicarbonyl glycation
    Mingzhan Xue
    Clinical Sciences Research Laboratories, Warwick Medical School, University of Warwick, University Hospital, Coventry CV2 2DX, UK
    Biochem J 443:213-22. 2012

Research Grants

  1. INHIBITION OF THE ANTICANCER TARGET GLYOXALASE I
    DONALD CREIGHTON; Fiscal Year: 2003
  2. Alzheimer's Disease Drugs
    DAVID VANDER JAGT; Fiscal Year: 2008
  3. Oxidative Stress, VEGF and Retinopathy
    DAVID VANDER JAGT; Fiscal Year: 2004
  4. How Substrates Activate Fumarase and Glyoxalase Evolved
    Irwin Rose; Fiscal Year: 2005
  5. GENOMIC ENZYMOLOGY: THE ENOLASE SUPERFAMILY
    JOHN GERLT; Fiscal Year: 2006
  6. GENOMIC ENZYMOLOGY: THE CROTONASE SUPERFAMILY
    JOHN GERLT; Fiscal Year: 2003
  7. ENZYMOLOGY OF ANTIBIOTIC RESISTANCE
    Richard Armstrong; Fiscal Year: 2007
  8. Progenitor Cell Dysfunction and Impaired Vasculogenesis*
    Michael Brownlee; Fiscal Year: 2008
  9. INTRACELLULAR GLYCATION AND DIABETIC COMPLICATIONS
    Michael Brownlee; Fiscal Year: 2006
  10. INTRACELLULAR GLYCATION AND DIABETIC COMPLICATIONS
    Michael Brownlee; Fiscal Year: 2007

Detail Information

Publications179 found, 100 shown here

  1. pmc Curcumin inhibits glyoxalase 1: a possible link to its anti-inflammatory and anti-tumor activity
    Thore Santel
    Institute of Biochemistry, University of Leipzig, Leipzig, Germany
    PLoS ONE 3:e3508. 2008
    ..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...
  2. pmc Hyperglycemia-induced reactive oxygen species increase expression of the receptor for advanced glycation end products (RAGE) and RAGE ligands
    Dachun Yao
    Department of Medicine, Diabetes Research Center, Albert Einstein College of Medicine, Bronx, New York, USA
    Diabetes 59:249-55. 2010
    ..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...
  3. ncbi Glyoxalase I--structure, function and a critical role in the enzymatic defence against glycation
    P J Thornalley
    Department of Biological Sciences, University of Essex, Central Campus, Wivenhoe Park, Colchester, Essex CO4 3SQ, U K
    Biochem Soc Trans 31:1343-8. 2003
    ..Glyoxalase I has a critical role in the prevention of glycation reactions mediated by methylglyoxal, glyoxal and other alpha-oxoaldehydes in vivo...
  4. pmc Protein and nucleotide damage by glyoxal and methylglyoxal in physiological systems--role in ageing and disease
    Paul J Thornalley
    Protein Damage and Systems Biology Research Group, Clinical Sciences Research Institute, Warwick Medical School, University of Warwick, University Hospital, Coventry, UK
    Drug Metabol Drug Interact 23:125-50. 2008
    ..Latest research suggests there are functional modifications of this process--implying a role in cell signalling, ageing and disease...
  5. ncbi Glyoxalase in tumourigenesis and multidrug resistance
    Paul J Thornalley
    Clinical Sciences Research Institute, Warwick Medical School, University of Warwick, University Hospital, Coventry, UK
    Semin Cell Dev Biol 22:318-25. 2011
    ..Further research is required urgently for next stage clinical translation. Finally, overexpression of glyoxalase 1 may be linked to multidrug resistance in chemotherapy of other disease - such as microbial infections...
  6. pmc The glyoxalase system: new developments towards functional characterization of a metabolic pathway fundamental to biological life
    P J Thornalley
    Department of Chemistry and Biological Chemistry, University of Essex, Colchester, U K
    Biochem J 269:1-11. 1990
  7. pmc Glyoxalase 1 increases anxiety by reducing GABAA receptor agonist methylglyoxal
    Margaret G Distler
    Department of Pathology, University of Chicago, Chicago, Illinois 60637, USA
    J Clin Invest 122:2306-15. 2012
    ..Finally, we demonstrated that pharmacological inhibition of GLO1 reduced anxiety, suggesting that GLO1 is a possible target for the treatment of anxiety disorders...
  8. pmc The critical role of S-lactoylglutathione formation during methylglyoxal detoxification in Escherichia coli
    Ertan Ozyamak
    School of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK
    Mol Microbiol 78:1577-90. 2010
    ..The data are discussed in terms of how cell fate is determined by the relative abundance of the enzymes and KefGB...
  9. ncbi Molecular enzymology of the glyoxalase system
    Bengt Mannervik
    Department of Biochemistry and Organic Chemistry, Uppsala University, Biomedical Center, Uppsala, Sweden
    Drug Metabol Drug Interact 23:13-27. 2008
    ..Both enzymes appear linked to a variety of pathological conditions, but further investigations are required to clarify the different physiological aspects of the glyoxalase system...
  10. ncbi Transcriptional control of glyoxalase 1 by Nrf2 provides a stress-responsive defence against dicarbonyl glycation
    Mingzhan Xue
    Clinical Sciences Research Laboratories, Warwick Medical School, University of Warwick, University Hospital, Coventry CV2 2DX, UK
    Biochem J 443:213-22. 2012
    ..We conclude that dicarbonyl stress is countered by up-regulation of Glo1 in the Nrf2 stress-responsive system, protecting protein and DNA from increased damage and preserving cell function...
  11. pmc Overexpression of glyoxalase-I reduces hyperglycemia-induced levels of advanced glycation end products and oxidative stress in diabetic rats
    Olaf Brouwers
    Department of Internal Medicine, Division of General Internal Medicine, Laboratory for Metabolism and Vascular Medicine, Maastricht University Medical Center, 6202 AZ Maastricht, The Netherlands
    J Biol Chem 286:1374-80. 2011
    ..The reduction of oxidative stress by GLO-I overexpression directly demonstrates the link between glycation and oxidative stress...
  12. ncbi Methylglyoxal causes strong weakening of detoxifying capacity and apoptotic cell death in rat hippocampal neurons
    Silvia Di Loreto
    Institute for Organ Transplantation and Immunocytology ITOI, CNR, P le Collemaggio, 67100 L Aquila, Italy
    Int J Biochem Cell Biol 40:245-57. 2008
    ..This, in turn, triggers widespread apoptotic cell death, occurring through the convergence of both mitochondrial and Fas-receptor pathways...
  13. pmc A common and unstable copy number variant is associated with differences in Glo1 expression and anxiety-like behavior
    Richard Williams
    Committee on Computational Neuroscience, University of Chicago, Chicago, Illinois, United States of America
    PLoS ONE 4:e4649. 2009
    ..Finally, these data provide an example of biologically significant phenotypic variability in model organisms that can be attributed to CNVs...
  14. ncbi Protecting the genome: defence against nucleotide glycation and emerging role of glyoxalase I overexpression in multidrug resistance in cancer chemotherapy
    P J Thornalley
    Department of Biological Sciences, University of Essex, Central Campus, Wivenhoe Park, Colchester, Essex CO4 3SQ, U K
    Biochem Soc Trans 31:1372-7. 2003
    ..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...
  15. ncbi Soluble receptor for advanced glycation end-products (sRAGE) and polymorphisms of RAGE and glyoxalase I genes in patients with pancreas cancer
    Tomas Krechler
    Department of Medicine IV Department of Gastroenterology and Hepatology, 1st Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic
    Clin Biochem 43:882-6. 2010
    ..sRAGE, soluble RAGE, is an inhibitor of pathological effects mediated via RAGE. The aim was to study sRAGE and polymorphisms of RAGE (AGER) and GLO genes in patients with pancreas cancer (PC)...
  16. ncbi Bacterial glyoxalase enzymes
    Uthaiwan Suttisansanee
    Department of Chemistry, University of Waterloo, Waterloo, Ontario, Canada
    Semin Cell Dev Biol 22:285-92. 2011
    ..In addition, the possibility of targeting inhibitors against the bacterial versus human enzyme has the potential to lead to new approaches to combat bacterial infections...
  17. ncbi Glyoxalase in ageing
    Mingzhan Xue
    Clinical Sciences Research Institute, Warwick Medical School, University of Warwick, University Hospital, Coventry, UK
    Semin Cell Dev Biol 22:293-301. 2011
    ..The glyoxalase system and Glo1 expression particularly is therefore likely linked to healthy ageing...
  18. ncbi A419C (E111A) polymorphism of the glyoxalase I gene and vascular complications in chronic hemodialysis patients
    Marta Kalousova
    Institute of Clinical Chemistry and Laboratory Diagnostics, First Faculty of Medicine and General University Hospital, Charles University, Prague, Czech Republic
    Ann N Y Acad Sci 1126:268-71. 2008
    ..In summary, in this study we demonstrate for the first time the association of A419C polymorphism of the glyoxalase I gene with sRAGE levels and show the genetic predisposition to vascular complications in HD patients...
  19. ncbi Genomic sequence of human glyoxalase-I: analysis of promoter activity and its regulation
    S Ranganathan
    Department of Pharmacology, Fox Chase Cancer Center, 7701 Burholme Avenue, Philadelphia, PA, USA
    Gene 240:149-55. 1999
    ..Knowledge regarding the regulation of glyoxalase-I may provide insights into the importance of this enzyme in human diseases...
  20. ncbi Increased glyoxalase I levels inhibit accumulation of oxidative stress and an advanced glycation end product in mouse mesangial cells cultured in high glucose
    Ki Mo Kim
    Diabetic Complications Research Center, Division of Traditional Korean Medicine TKM Integrated Research, Korea Institute of Oriental Medicine KIOM, 483 Exporo, Yuseong Gu, Daejeon 305 811, South Korea
    Exp Cell Res 318:152-9. 2012
    ..These results suggest that GLO-1 plays a role in high glucose-mediated signaling by reducing MG accumulation and oxidative stress in diabetes mellitus...
  21. ncbi The formation of argpyrimidine, a methylglyoxal-arginine adduct, in the nucleus of neural cells
    Yusuke Nakadate
    Department of Bioengineering, Graduate School of Engineering, Osaka City University, 3 3 138 Sugimoto, Sumiyoshi ku, Osaka 558 8585, Japan
    Biochem Biophys Res Commun 378:209-12. 2009
    ..Argpyrimidine may contribute to the neural differentiation and/or the maintenance of the differentiated state via the modification of nuclear proteins...
  22. ncbi Mechanistic diversity in a metalloenzyme superfamily
    R N Armstrong
    Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 0146, USA
    Biochemistry 39:13625-32. 2000
    ..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...
  23. pmc GLO1 overexpression in human malignant melanoma
    Warner B Bair
    Department of Pharmacology and Toxicology, College of Pharmacy and Arizona Cancer Center, University of Arizona, Tucson, USA
    Melanoma Res 20:85-96. 2010
    Glyoxalase I [lactoylglutathione lyase (EC 4.4.1.5) encoded by GLO1] is a ubiquitous cellular defense enzyme involved in the detoxification of methylglyoxal, a cytotoxic byproduct of glycolysis...
  24. pmc Genetic engineering of the glyoxalase pathway in tobacco leads to enhanced salinity tolerance
    S L Singla-Pareek
    Plant Molecular Biology, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi 110 067, India
    Proc Natl Acad Sci U S A 100:14672-7. 2003
    ..These findings establish the potential of manipulation of the glyoxalase pathway for increased salinity tolerance without affecting yield in crop plants...
  25. ncbi Proteomic study reveals that proteins involved in metabolic and detoxification pathways are highly expressed in HER-2/neu-positive breast cancer
    Daohai Zhang
    Department of Laboratory Medicine, National University Hospital, 5 Lower Kent Ridge Road, Singapore 119074
    Mol Cell Proteomics 4:1686-96. 2005
    ....
  26. ncbi Reduced expression of glyoxalase-1 mRNA in mood disorder patients
    Michiko Fujimoto
    Division of Neuropsychiatry, Department of Neuroscience, Yamaguchi University Graduate School of Medicine, 1 1 1 Minamikogushi, Ube, Yamaguchi 755 8505, Japan
    Neurosci Lett 438:196-9. 2008
    ..These results suggest that the aberrant expression of Glo1 might be involved in the pathophysiology of mood disorders...
  27. ncbi Transgenic tobacco plants overexpressing glyoxalase enzymes resist an increase in methylglyoxal and maintain higher reduced glutathione levels under salinity stress
    Sudesh Kumar Yadav
    Plant Molecular Biology Laboratory, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi 110 067, India
    FEBS Lett 579:6265-71. 2005
    ....
  28. ncbi Exercise prevents sleep deprivation-associated anxiety-like behavior in rats: potential role of oxidative stress mechanisms
    Craig Vollert
    Department of Pharmacological and Pharmaceutical Sciences, University of Houston, Texas, USA
    Behav Brain Res 224:233-40. 2011
    ..It is plausible that oxidative stress via regulation of GLO1 and GSR1 is involved in sleep deprivation-induced anxiety-like behavior of rats...
  29. ncbi Glyoxalase 1 and glutathione reductase 1 regulate anxiety in mice
    Iiris Hovatta
    The Salk Institute for Biological Studies, Laboratory of Genetics, 10010 North Torrey Pines Road, La Jolla, California 92037, USA
    Nature 438:662-6. 2005
    ..Both of these genes are involved in oxidative stress metabolism, linking this pathway with anxiety-related behaviour...
  30. ncbi Effect of pyridoxamine on chemical modification of proteins by carbonyls in diabetic rats: characterization of a major product from the reaction of pyridoxamine and methylglyoxal
    Ram H Nagaraj
    Center for Vision Research, Department of Ophthalmology, Case Western Reserve University and University Hospitals of Cleveland, Wearn Building, Room 643, Cleveland, OH 44106, USA
    Arch Biochem Biophys 402:110-9. 2002
    ..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...
  31. ncbi Age- and stage-dependent glyoxalase I expression and its activity in normal and Alzheimer's disease brains
    Björn Kuhla
    Neuroimmunological Cell Biology Unit, IZKF Leipzig, Inselstrasse 22, 04103 Leipzig, Germany
    Neurobiol Aging 28:29-41. 2007
    ..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...
  32. ncbi Identification of glyoxalase 1 polymorphisms associated with enzyme activity
    Raitis Peculis
    Latvian Biomedical Research and Study Centre, Ratsupites str 1, Riga, LV 1067, Latvia
    Gene 515:140-3. 2013
    ..SNPs in GLO1 can be used to predict enzyme activity and detoxifying capabilities, but further studies are needed to link these SNPs with common complications in diabetes...
  33. ncbi Role of glyoxalase I in the proliferation and apoptosis control of human LNCaP and PC3 prostate cancer cells
    Cinzia Antognelli
    Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy
    Prostate 73:121-32. 2013
    ..The aim of the present work was to clarify whether GLOI was involved in the proliferation control of LNCaP and PC3 human prostate cancer cells or might play a different role in the growth regulation of these cells...
  34. ncbi Microbial glyoxalase enzymes: metalloenzymes controlling cellular levels of methylglyoxal
    Nicole Sukdeo
    Department of Chemistry, University of Waterloo, 200 University Avenue, Waterloo, Ontario N2L 3G1, Canada
    Drug Metabol Drug Interact 23:29-50. 2008
    ..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+...
  35. pmc A pilot study on the use of serum glyoxalase as a supplemental biomarker to predict malignant cases of the prostate in the PSA range of 4-20 ng/ml
    Sushant V Chavan
    Department of Biochemistry, MGM Medical College and General Hospital, Navi Mumbai, India
    Indian J Med Res 134:458-62. 2011
    ..This study was aimed at exploring the use of serum glyoxalase as a supplemental biomarker to differentiate between malignant vs non-malignant diseases of the prostate in patients with PSA in the range of 4-20 ng/ml...
  36. ncbi Contents of D-lactate and its related metabolites as well as enzyme activities in the liver, muscle and blood plasma of aging rats
    M Kawase
    Faculty of Pharmaceutical Sciences, Department of Physiological Chemistry, Okayama University Tsushima Naka, Japan
    Mech Ageing Dev 84:55-63. 1995
    ..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...
  37. pmc Characterisation of glyoxalase I in a streptozocin-induced mouse model of diabetes with painful and insensate neuropathy
    M M Jack
    Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, KS 66160, USA
    Diabetologia 54:2174-82. 2011
    ..We hypothesised that differential GLO1 levels in sensory neurons may lead to differences in AGE formation and modulate the phenotype of DN...
  38. pmc Decreasing intracellular superoxide corrects defective ischemia-induced new vessel formation in diabetic mice
    Daniel J Ceradini
    Department of Surgery, Stanford University School of Medicine, Stanford, California 94305 5148, USA
    J Biol Chem 283:10930-8. 2008
    ..These results provide a basis for the rational design of new therapeutics to normalize impaired ischemia-induced vasculogenesis in patients with diabetes...
  39. ncbi Glyoxalase I of the malarial parasite Plasmodium falciparum: evidence for subunit fusion
    Rimma Iozef
    Interdisciplinary Research Center, Justus Liebig University, Heinrich Buff Ring 26 32, D 35392 Giessen, Germany
    FEBS Lett 554:284-8. 2003
    ..These results support the hypothesis of domain-swapping and subunit fusion as mechanisms in glyoxalase I evolution...
  40. ncbi Proteomic analysis defines altered cellular redox pathways and advanced glycation end-product metabolism in glomeruli of db/db diabetic mice
    Michelle T Barati
    Department of Medicine, University of Louisville, Louisville, Kentucky 40202, USA
    Am J Physiol Renal Physiol 293:F1157-65. 2007
    ....
  41. pmc Glyoxalase I polymorphism rs2736654 causing the Ala111Glu substitution modulates enzyme activity--implications for autism
    Madhabi Barua
    Department of Developmental Biochemistry, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York, NY 10314, USA
    Autism Res 4:262-70. 2011
    ..We suggest that accumulation of MG results in the formation of AGEs, which induce expression of the RAGE that during crucial neuronal development may be a factor in the pathology of autism...
  42. ncbi Glyoxalase I and aldose reductase gene polymorphisms and susceptibility to carotid atherosclerosis in type 2 diabetes
    Jing cheng Wu
    Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated First People s Hospital, Shanghai, PR China
    Genet Test Mol Biomarkers 15:273-9. 2011
    ..To investigate the association of polymorphisms of glyoxalase I (GLO1) A419C, GLO1 C-7T, and aldose reductase C-106T with type 2 diabetes and diabetic carotid atherosclerosis in a Chinese Han population...
  43. ncbi Genetic predisposition to advanced glycation end products toxicity is related to prognosis of chronic hemodialysis patients
    Marta Kalousova
    Institute of Clinical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic
    Kidney Blood Press Res 33:30-6. 2010
    ..The A419C (E111A) polymorphism of the GLO I gene is associated with vascular disease in hemodialysis (HD) patients and some RAGE gene polymorphisms are implicated in various pathological states...
  44. ncbi Yeast glyoxalase I is a monomeric enzyme with two active sites
    E M Frickel
    Department of Biochemistry, Uppsala University, Biochemical Center, Box 576, SE-75123 Uppsala, Sweden
    J Biol Chem 276:1845-9. 2001
    ..Yeast glyoxalase I appears to be one of the few enzymes that are present as a single polypeptide with two active sites that catalyze the same reaction...
  45. ncbi Novel regulatory system nemRA-gloA for electrophile reduction in Escherichia coli K-12
    Changhan Lee
    Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Yuseong Gu, Daejeon 305 701, Korea
    Mol Microbiol 88:395-412. 2013
    ..Therefore, we propose that cells have a cytosolic system consisting of the nemRA-gloA operon for the reduction of electrophiles, especially quinones and glyoxals, to maintain an appropriate intracellular redox balance...
  46. pmc CYP17, GSTP1, PON1 and GLO1 gene polymorphisms as risk factors for breast cancer: an Italian case-control study
    Cinzia Antognelli
    Department of Experimental Medicine, University of Perugia, Perugia, Italy
    BMC Cancer 9:115. 2009
    ..In the present case-control study, we investigated the possible association of CYP17 A1A2, GSTP1 ILE105VAL, PON1 Q192R or L55M, and GLO1 A111E polymorphisms with the risk of BC...
  47. ncbi Scavenging system efficiency is crucial for cell resistance to ROS-mediated methylglyoxal injury
    Fernanda Amicarelli
    Department of Basic and Applied Biology, Faculty of Science, L Aquila University, L Aquila, Italy
    Free Radic Biol Med 35:856-71. 2003
    ..These data emphasize the pivotal role of antioxidant and detoxifying systems in determining the grade of sensitivity of cells to methylglyoxal...
  48. pmc Role for glyoxalase I in Alzheimer's disease
    Feng Chen
    Division of Psychiatry Research, University of Zurich, August Forel Strasse 1, 8008 Zurich, Switzerland
    Proc Natl Acad Sci U S A 101:7687-92. 2004
    ..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...
  49. ncbi Troglitazone selectively inhibits glyoxalase I gene expression
    L Wu
    Department of Anatomy and Cell Biology, College of Medicine, University of Saskatchewan, Saskatoon, SK, Canada
    Diabetologia 44:2004-12. 2001
    ..This inhibition of the glyoxalase system could contribute to troglitazone's hepatotoxic action which has previously been reported in a small percentage of individuals...
  50. ncbi Glyoxalase I overexpression ameliorates renal ischemia-reperfusion injury in rats
    Takanori Kumagai
    Div of Nephrology and Endocrinology, Univ of Tokyo School of Medicine, 7 3 1 Hongo, Bunkyo ku, Tokyo 113 8655, Japan
    Am J Physiol Renal Physiol 296:F912-21. 2009
    ..In conclusion, glyoxalase I exerts renoprotective effects in renal I/R injury via a reduction in MG accumulation in tubular cells...
  51. ncbi Glyoxalase I A111E, paraoxonase 1 Q192R and L55M polymorphisms: susceptibility factors of multiple sclerosis?
    A Sidoti
    Department of Biomorphology and Biotechnologies, University of Messina, 98100, Italy
    Mult Scler 13:446-53. 2007
    ..The two polymorphisms appear to be common genetic traits that are associated with an increased risk for MS--the analysis of both, in each single case, may be a revealing predictable factor for MS risk...
  52. ncbi Specificity of the trypanothione-dependent Leishmania major glyoxalase I: structure and biochemical comparison with the human enzyme
    Antonio Ariza
    Division of Biological Chemistry and Molecular Microbiology, Wellcome Trust Biocentre, School of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK
    Mol Microbiol 59:1239-48. 2006
    ..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...
  53. ncbi An XAS investigation of product and inhibitor complexes of Ni-containing GlxI from Escherichia coli: mechanistic implications
    G Davidson
    Department of Chemistry, University of Massachusetts, Amherst, Massachusetts 01003, USA
    Biochemistry 40:4569-82. 2001
    ..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...
  54. ncbi Glyoxalase I inhibitors in cancer chemotherapy
    D J Creighton
    Department of Chemistry and Biochemistry, University of Maryland, Baltimore County, MD, U S A
    Biochem Soc Trans 31:1378-82. 2003
    ..Finally, a preliminary evaluation of the efficacy of selected GlxI inhibitors in tumour-bearing mice is given...
  55. ncbi Alteration of glyoxalase genes expression in response to testosterone in LNCaP and PC3 human prostate cancer cells
    Cinzia Antognelli
    Department of Experimental Medicine, University of Perugia, Perugia, Italy
    Cancer Biol Ther 6:1880-8. 2007
    ..Knowledge regarding the regulation of glyoxalases by testosterone may provide insights into the importance of these enzymes in human prostate carcinomas in vivo...
  56. ncbi Methylglyoxal-mediated anxiolysis involves increased protein modification and elevated expression of glyoxalase 1 in the brain
    Boris Hambsch
    Department of Behavioral Neuroendocrinology, Max Planck Institute of Psychiatry, Munich, Germany
    J Neurochem 113:1240-51. 2010
    ..Thereby, we identified a novel molecular mechanism for anxiety-related behavior in mice that may help to elucidate genesis of psychiatric disorders in humans...
  57. ncbi Glyoxalase I from Leishmania donovani: a potential target for anti-parasite drug
    Prasad K Padmanabhan
    School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India
    Biochem Biophys Res Commun 337:1237-48. 2005
    ..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...
  58. ncbi Glyoxalase enzyme system in human muscular dystrophy
    N C Kar
    Clin Chim Acta 65:153-5. 1975
    ..The selective decrease of glyoxalase I activity in recessively inherited muscular dystrophies may have some relevance to some phases of these disease processes...
  59. ncbi Expression of glyoxalase I and II in normal and breast cancer tissues
    A Rulli
    Department of Surgical Sciences, University of Perugia, Italy
    Breast Cancer Res Treat 66:67-72. 2001
    ..Moreover, they suggest a possible employment of GI inhibitors as anti-cancer drugs...
  60. pmc Distinct classes of glyoxalase I: metal specificity of the Yersinia pestis, Pseudomonas aeruginosa and Neisseria meningitidis enzymes
    Nicole Sukdeo
    Department of Chemistry, University of Waterloo, 200 University Avenue, Waterloo, Ontario, Canada N2L 3G1
    Biochem J 384:111-7. 2004
    ..With respect to sequence alignments, these inserts may potentially contribute to defining the metal specificity of GlxI at a structural level...
  61. ncbi Detection and characterisation of the genes encoding glyoxalase I and II from Neisseria meningitidis
    G Kizil
    Division of Microbiology, School of Clinical Laboratory Sciences, University of Nottingham Faculty of Medicine and Health Sciences, University Hospital
    J Med Microbiol 49:669-73. 2000
    ..A databank search also revealed the presence of a putative gloB gene, encoding glyoxalase II (GlxII), in the recently released genomic sequences of Neisseria meningitidis and N. gonorrhoeae...
  62. ncbi Association analysis of the functional Ala111Glu polymorphism of the glyoxalase I gene in panic disorder
    Pierluigi Politi
    Department of Applied Health and Behavioural Sciences, Section of Psychiatry, University of Pavia, via Bassi 21, I 27100, Pavia, Italy
    Neurosci Lett 396:163-6. 2006
    ..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...
  63. ncbi Overproduction and characterization of a dimeric non-zinc glyoxalase I from Escherichia coli: evidence for optimal activation by nickel ions
    S L Clugston
    Department of Chemistry, University of Waterloo, Waterloo, Ontario, Canada N2L 3G1
    Biochemistry 37:8754-63. 1998
    ..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+...
  64. ncbi Oxidative stress is the new stress
    Jay A Gingrich
    Nat Med 11:1281-2. 2005
  65. pmc Glyoxalase I gene deletion mutants of Leishmania donovani exhibit reduced methylglyoxal detoxification
    Swati C Chauhan
    School of Life Sciences, Jawaharlal Nehru University, New Delhi, India
    PLoS ONE 4:e6805. 2009
    ..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...
  66. ncbi Quantitative assessment of the glyoxalase pathway in Leishmania infantum as a therapeutic target by modelling and computer simulation
    Marta Sousa Silva
    Centro de Quimica e Bioquimica, Departmento de Química e Bioquímica, Faculdade de Ciencias da Universidade de Lisboa, Portugal
    FEBS J 272:2388-98. 2005
    ..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...
  67. ncbi Phosphorylation on Thr-106 and NO-modification of glyoxalase I suppress the TNF-induced transcriptional activity of NF-kappaB
    Virginie de Hemptinne
    Faculty of Medicine and Health Sciences, VIB Department of Medical Protein Research, University of Ghent, Albert Baertsoenkaai 3, 9000, Ghent, Belgium
    Mol Cell Biochem 325:169-78. 2009
    ..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...
  68. ncbi Glyoxalase-1 prevents mitochondrial protein modification and enhances lifespan in Caenorhabditis elegans
    Michael Morcos
    Department of Medicine I and Clinical Chemistry, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany
    Aging Cell 7:260-9. 2008
    ..elegans lifespan. In contrast, knock-down of CeGly increases MG modifications of mitochondrial proteins and mitochondrial ROS production, and decreases C. elegans lifespan...
  69. ncbi Lack of evidence to support the glyoxalase 1 gene (GLO1) as a risk gene of autism in Han Chinese patients from Taiwan
    Yu Yu Wu
    Department of Child Psychiatry, Chang Gung Children s Hospital, Kewi Shan, Taiwan
    Prog Neuropsychopharmacol Biol Psychiatry 32:1740-4. 2008
    ..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...
  70. ncbi No association between common variants in glyoxalase 1 and autism spectrum disorders
    Karola Rehnstrom
    Department of Molecular Medicine, National Public Health Institute, Helsinki, Finland karola
    Am J Med Genet B Neuropsychiatr Genet 147:124-7. 2008
    ..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...
  71. pmc Tumour necrosis factor induces phosphorylation primarily of the nitric-oxide-responsive form of glyoxalase I
    Virginie de Hemptinne
    Department of Medical Protein Research, Molecular and Metabolic Signaling Unit, VIB, 9000 Ghent, Belgium
    Biochem J 407:121-8. 2007
    ..In summary, these data suggest that the TNF-induced phosphorylation of GLO1 is the dominant factor for cell death...
  72. pmc Case-control and family-based association studies of candidate genes in autistic disorder and its endophenotypes: TPH2 and GLO1
    Roberto Sacco
    Laboratory of Molecular Psychiatry and Neurogenetics, University Campus Bio Medico, Via Longoni 83, I 00155 Rome, Italy
    BMC Med Genet 8:11. 2007
    ..Hyperserotoninemia, macrocephaly, and peptiduria represent some of the best-characterized endophenotypes in autism research...
  73. ncbi Polyproline-rod approach to isolating protein targets of bioactive small molecules: isolation of a new target of indomethacin
    Shin ichi Sato
    The Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas 77030, USA
    J Am Chem Soc 129:873-80. 2007
    ..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...
  74. pmc Trypanothione-dependent glyoxalase I in Trypanosoma cruzi
    Neil Greig
    Division of Biological Chemistry and Molecular Microbiology, Wellcome Trust Biocentre, College of Life Sciences, University of Dundee, Dundee, DD1 5EH, Scotland, UK
    Biochem J 400:217-23. 2006
    ..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...
  75. ncbi Candidate genes of anxiety-related behavior in HAB/LAB rats and mice: focus on vasopressin and glyoxalase-I
    Rainer Landgraf
    Max Planck Institute of Psychiatry, Munich, Germany
    Neurosci Biobehav Rev 31:89-102. 2007
    ....
  76. ncbi Protein biomarkers in a mouse model of extremes in trait anxiety
    Claudia Ditzen
    Max Planck Institute of Psychiatry, D 80804 Munich, Germany
    Mol Cell Proteomics 5:1914-20. 2006
    ..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...
  77. ncbi Unease on the role of glyoxalase 1 in high-anxiety-related behaviour
    Paul J Thornalley
    Disease Mechanisms and Therapeutics Research Group, Department of Biological Sciences, University of Essex, Wivenhoe Park, Colchester, Essex CO4 3Q4, UK
    Trends Mol Med 12:195-9. 2006
    ....
  78. ncbi Upregulation of glyoxalase I fails to normalize methylglyoxal levels: a possible mechanism for biochemical changes in diabetic mouse lenses
    Magdalena M Staniszewska
    Department of Ophthalmology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA
    Mol Cell Biochem 288:29-36. 2006
    ....
  79. ncbi Glyoxalase I is critical for human retinal capillary pericyte survival under hyperglycemic conditions
    Antonia G Miller
    Department of Ophthalmology, Case Western Reserve University, Cleveland, Ohio 44106, USA
    J Biol Chem 281:11864-71. 2006
    ..may contribute to pericyte death by apoptosis during the early stages of diabetic retinopathy...
  80. ncbi Identification of glyoxalase-I as a protein marker in a mouse model of extremes in trait anxiety
    Simone A Krömer
    Max Planck Institute of Psychiatry, D 80804 Munich, Germany
    J Neurosci 25:4375-84. 2005
    ..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...
  81. ncbi Deficiency in short-chain fatty acid beta-oxidation affects theta oscillations during sleep
    Mehdi Tafti
    Biochemistry and Genetics Unit, Department of Psychiatry, University of Geneva and Geneva University Hospitals, Chemin du Petit Bel Air 2, 1225 Chene Bourg, Switzerland
    Nat Genet 34:320-5. 2003
    ..Thus, an underappreciated metabolic pathway involving fatty acid beta-oxidation also regulates theta oscillations during sleep...
  82. ncbi The role of glyoxalase I in the detoxification of methylglyoxal and in the activation of the KefB K+ efflux system in Escherichia coli
    M J Maclean
    Department of Molecular and Cell Biology, Institute of Medical Sciences, University of Aberdeen, Foresterhill, UK
    Mol Microbiol 27:563-71. 1998
    ..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...
  83. pmc 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
    Franky Van Herreweghe
    Department of Medical Protein Research, Ghent University and Flanders Interuniversity Institute for Biotechnology, K L Ledeganckstraat 35, B 9000 Ghent, Belgium
    Proc Natl Acad Sci U S A 99:949-54. 2002
    ....
  84. ncbi Reaction mechanism of glyoxalase I explored by an X-ray crystallographic analysis of the human enzyme in complex with a transition state analogue
    A D Cameron
    Department of Molecular Biology, Uppsala University, Biomedical Center, Sweden
    Biochemistry 38:13480-90. 1999
    ..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...
  85. ncbi Anti-glycation defences in yeast
    A Ponces Freire
    Departamento de Quimica e Bioquimica, Faculdade de Ciencias da Universidade de Lisboa, Edíficio C8 1749 016 Lisbon, Portugal
    Biochem Soc Trans 31:1409-12. 2003
    ..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...
  86. ncbi Glyoxalase I is involved in resistance of human leukemia cells to antitumor agent-induced apoptosis
    H Sakamoto
    Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo, Japan
    Blood 95:3214-8. 2000
    ..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...
  87. ncbi Determination of the structure of Escherichia coli glyoxalase I suggests a structural basis for differential metal activation
    M M He
    Howard Hughes Medical Institute, Institute of Molecular Biology, Department of Physics, 1229 University of Oregon, Eugene, Oregon 97403 1229, USA
    Biochemistry 39:8719-27. 2000
    ..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...
  88. ncbi In situ kinetic analysis of glyoxalase I and glyoxalase II in Saccharomyces cerevisiae
    A M Martins
    Grupo de Enzimologia, , , Portugal
    Eur J Biochem 268:3930-6. 2001
    ..The possible causes for the discrepancy between data obtained from initial rate analysis and progress curve analysis, for glyoxalase II, are discussed...
  89. ncbi Selective activation of apoptosis program by S-p-bromobenzylglutathione cyclopentyl diester in glyoxalase I-overexpressing human lung cancer cells
    H Sakamoto
    Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo 170 8455, Japan
    Clin Cancer Res 7:2513-8. 2001
    ..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...
  90. ncbi Glyoxalase I deficiency is associated with an unusual level of advanced glycation end products in a hemodialysis patient
    T Miyata
    Molecular and Cellular Nephrology, Institute of Medical Sciences and Department of Medicine, Tokai University School of Medicine, and Bohsei Hiratsuka Clinic, Kanagawa, Japan
    Kidney Int 60:2351-9. 2001
    ..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...
  91. pmc Optimized heterologous expression of the human zinc enzyme glyoxalase I
    M Ridderström
    Department of Biochemistry, Uppsala University, Biomedical Center, Sweden
    Biochem J 314:463-7. 1996
    ..The kinetic properties of recombinant glyoxalase I were indistinguishable from those of the enzyme purified from human tissues...
  92. pmc Crystal structure of human glyoxalase I--evidence for gene duplication and 3D domain swapping
    A D Cameron
    Department of Molecular Biology, Uppsala University, Biomedical Center, Sweden
    EMBO J 16:3386-95. 1997
    ..This structural family appears to allow members to form with or without domain swapping...
  93. ncbi Glyoxalase I polymorphism in the mouse: a new genetic marker linked to H-2
    T Meo
    Science 198:311-3. 1977
    ..Several features of the Glo-1 polymorphism in the mouse recommend it as a marker of choice for the H-2 region...
  94. pmc Proteomic studies identified a single nucleotide polymorphism in glyoxalase I as autism susceptibility factor
    Mohammed A Junaid
    Department of Developmental Biochemistry, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York
    Am J Med Genet A 131:11-7. 2004
    ..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...
  95. ncbi Cloning and characterization of human colon glyoxalase-I
    S Ranganathan
    Department of Pharmacology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111
    J Biol Chem 268:5661-7. 1993
    ..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...
  96. ncbi Molecular characterization of glyoxalase-I from a higher plant; upregulation by stress
    J Espartero
    Instituto de Recursos Naturales y Agrobiologia, C S I C, Sevilla, Spain
    Plant Mol Biol 29:1223-33. 1995
    ..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...
  97. pmc A trypanothione-dependent glyoxalase I with a prokaryotic ancestry in Leishmania major
    Tim J Vickers
    Division of Biological Chemistry and Molecular Microbiology, Wellcome Trust Biocentre, School of Life Sciences, University of Dundee, DD1 5EH Dundee, Scotland
    Proc Natl Acad Sci U S A 101:13186-91. 2004
    ..This trypanothione-dependent glyoxalase I is therefore an attractive focus for additional biochemical and genetic investigation as a possible target for rational drug design...
  98. ncbi Methylglyoxal metabolism and diabetic complications: roles of aldose reductase, glyoxalase-I, betaine aldehyde dehydrogenase and 2-oxoaldehyde dehydrogenase
    David L Vander Jagt
    Department of Biochemistry and Molecular Biology, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA
    Chem Biol Interact 143:341-51. 2003
    ..There are two NADP-dependent 2-ODHs in human liver. Both of these require an activating amine. The physiological activator is unknown...
  99. pmc Involvement of the detoxifying enzyme lactoylglutathione lyase in Streptococcus mutans aciduricity
    Bryan Korithoski
    Dental Research Institute, University of Toronto, 124 Edward St, Toronto, Ontario, Canada M5G 1G6
    J Bacteriol 189:7586-92. 2007
    ..mutans. Proteome analysis of S. mutans demonstrated that lactoylglutathione lyase (LGL) was up-regulated during acid challenge...
  100. ncbi Ethyl pyruvate and ethyl lactate down-regulate the production of pro-inflammatory cytokines and modulate expression of immune receptors
    Marcus Hollenbach
    University of Leipzig, Institute of Biochemistry, Johannisallee 30, 04103 Leipzig, Germany
    Biochem Pharmacol 76:631-44. 2008
    ..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...
  101. ncbi Methylglyoxal synthetase, enol-pyruvaldehyde, glutathione and the glyoxalase system
    Irwin A Rose
    Department of Physiology and Biophysics, University of California, Irvine, Irvine, California 92717 1700, USA
    J Am Chem Soc 124:13047-52. 2002
    ....

Research Grants10

  1. INHIBITION OF THE ANTICANCER TARGET GLYOXALASE I
    DONALD CREIGHTON; Fiscal Year: 2003
    ..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. ..
  2. Alzheimer's Disease Drugs
    DAVID VANDER JAGT; Fiscal Year: 2008
    ..Versatile schemes to synthesize analogs of resveratrol have been developed. The Specific Aim of this proposal is to test resveratrol and analogs in an animal model of Alzheimer's disease. [unreadable] [unreadable] [unreadable]..
  3. Oxidative Stress, VEGF and Retinopathy
    DAVID VANDER JAGT; Fiscal Year: 2004
    ..It provides a testable model that connects hyperglycemia-> oxidative stress-> growth factors-> diabetic retinopathy. ..
  4. How Substrates Activate Fumarase and Glyoxalase Evolved
    Irwin Rose; Fiscal Year: 2005
    ..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. ..
  5. GENOMIC ENZYMOLOGY: THE ENOLASE SUPERFAMILY
    JOHN GERLT; Fiscal Year: 2006
    ..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. ..
  6. GENOMIC ENZYMOLOGY: THE CROTONASE SUPERFAMILY
    JOHN GERLT; Fiscal Year: 2003
    ..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. ..
  7. ENZYMOLOGY OF ANTIBIOTIC RESISTANCE
    Richard Armstrong; Fiscal Year: 2007
    ..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. ..
  8. Progenitor Cell Dysfunction and Impaired Vasculogenesis*
    Michael Brownlee; Fiscal Year: 2008
    ..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 [unreadable] [unreadable]..
  9. INTRACELLULAR GLYCATION AND DIABETIC COMPLICATIONS
    Michael Brownlee; Fiscal Year: 2006
    ..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. ..
  10. INTRACELLULAR GLYCATION AND DIABETIC COMPLICATIONS
    Michael Brownlee; Fiscal Year: 2007
    ..Supershift experiments will use commercially availableantibodies. IP-westernsof cell extracts will be immunoblotted with antibodies to glyoxalase I-substrate-derived advanced glycationendproducts. ..