aryldialkylphosphatase

Summary

Summary: An enzyme which catalyzes the hydrolysis of an aryl-dialkyl phosphate to form dialkyl phosphate and an aryl alcohol. It can hydrolyze a broad spectrum of organophosphate substrates and a number of aromatic carboxylic acid esters. It may also mediate an enzymatic protection of LOW DENSITY LIPOPROTEINS against oxidative modification and the consequent series of events leading to ATHEROMA formation. The enzyme was previously regarded to be identical with Arylesterase (EC 3.1.1.2).

Top Publications

  1. pmc Paraoxonase inhibits high-density lipoprotein oxidation and preserves its functions. A possible peroxidative role for paraoxonase
    M Aviram
    The Lipid Research Laboratory, Technion Faculty of Medicine, The Rappaport Family Institute for Research in the Medical Sciences and Rambam Medical Center, Haifa, Israel, 31096
    J Clin Invest 101:1581-90. 1998
  2. pmc Mechanisms underlying adverse effects of HDL on eNOS-activating pathways in patients with coronary artery disease
    Christian Besler
    Cardiology, Cardiovascular Center, University Hospital Zurich, Zurich, Switzerland
    J Clin Invest 121:2693-708. 2011
  3. ncbi Plasma paraoxonase, health, inflammatory conditions, and liver function in transition dairy cows
    M Bionaz
    Istituto di Zootecnica, Facolta di Agraria, Universita Cattolica del Sacro Cuore, Via Emilia Parmense 84, Piacenza, Italy
    J Dairy Sci 90:1740-50. 2007
  4. pmc Prenatal exposure to organophosphates, paraoxonase 1, and cognitive development in childhood
    Stephanie M Engel
    Department of Preventive Medicine, Mount Sinai School of Medicine, New York, New York, USA
    Environ Health Perspect 119:1182-8. 2011
  5. ncbi Paraoxonases 1, 2, and 3, oxidative stress, and macrophage foam cell formation during atherosclerosis development
    Michael Aviram
    The Lipid Research Laboratory, Technion Faculty of Medicine, The Rappaport Family Institute for Research in the Medical Sciences and Rambam Medical Center, 31096 Haifa, Israel
    Free Radic Biol Med 37:1304-16. 2004
  6. ncbi Oxidized LDL and HDL: antagonists in atherothrombosis
    A Mertens
    Center for Experimental Surgery and Anesthesiology, Katholieke Universiteit Leuven, Belgium
    FASEB J 15:2073-84. 2001
  7. ncbi Structure-reactivity studies of serum paraoxonase PON1 suggest that its native activity is lactonase
    Olga Khersonsky
    Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel
    Biochemistry 44:6371-82. 2005
  8. doi Immunohistochemical analysis of paraoxonases-1 and 3 in human atheromatous plaques
    Judit Marsillach
    Centre de Recerca Biomedica, Hospital Universitari de Sant Joan, Institut d Investigacions Sanitaries Pere Virgili, Universitat Rovira i Virgili, Reus, Catalunya, Spain
    Eur J Clin Invest 41:308-14. 2011
  9. ncbi Modulation of paraoxonase (PON1) activity
    Lucio G Costa
    Department of Environmental and Occupational Health Sciences, University of Washington, 4225 Roosevelt Way NE, Suite 100, Seattle, WA 98105, USA
    Biochem Pharmacol 69:541-50. 2005
  10. doi The three-gene paraoxonase family: physiologic roles, actions and regulation
    Louis Philippe Precourt
    Research Centre, CHU Sainte Justine, Department of Nutrition, Universite de Montreal, Montreal, Quebec, Canada
    Atherosclerosis 214:20-36. 2011

Detail Information

Publications388 found, 100 shown here

  1. pmc Paraoxonase inhibits high-density lipoprotein oxidation and preserves its functions. A possible peroxidative role for paraoxonase
    M Aviram
    The Lipid Research Laboratory, Technion Faculty of Medicine, The Rappaport Family Institute for Research in the Medical Sciences and Rambam Medical Center, Haifa, Israel, 31096
    J Clin Invest 101:1581-90. 1998
    ..The presence of PON in HDL may thus be a major contributor to the antiatherogenicity of this lipoprotein...
  2. pmc Mechanisms underlying adverse effects of HDL on eNOS-activating pathways in patients with coronary artery disease
    Christian Besler
    Cardiology, Cardiovascular Center, University Hospital Zurich, Zurich, Switzerland
    J Clin Invest 121:2693-708. 2011
    ....
  3. ncbi Plasma paraoxonase, health, inflammatory conditions, and liver function in transition dairy cows
    M Bionaz
    Istituto di Zootecnica, Facolta di Agraria, Universita Cattolica del Sacro Cuore, Via Emilia Parmense 84, Piacenza, Italy
    J Dairy Sci 90:1740-50. 2007
    ..3 +/- 7.7 kg of milk/d during the first 30 DIM. A reduction in the ability of the liver to cope with the increased metabolic demand near parturition in dairy cows can be diagnosed using changes in baseline plasma PON...
  4. pmc Prenatal exposure to organophosphates, paraoxonase 1, and cognitive development in childhood
    Stephanie M Engel
    Department of Preventive Medicine, Mount Sinai School of Medicine, New York, New York, USA
    Environ Health Perspect 119:1182-8. 2011
    ..Prenatal exposure to organophosphate pesticides has been shown to negatively affect child neurobehavioral development. Paraoxonase 1 (PON1) is a key enzyme in the metabolism of organophosphates...
  5. ncbi Paraoxonases 1, 2, and 3, oxidative stress, and macrophage foam cell formation during atherosclerosis development
    Michael Aviram
    The Lipid Research Laboratory, Technion Faculty of Medicine, The Rappaport Family Institute for Research in the Medical Sciences and Rambam Medical Center, 31096 Haifa, Israel
    Free Radic Biol Med 37:1304-16. 2004
    ..Intervention to increase the paraoxonases (cellular and humoral) by dietary or pharmacological means can reduce macrophage foam cell formation and attenuate atherosclerosis development...
  6. ncbi Oxidized LDL and HDL: antagonists in atherothrombosis
    A Mertens
    Center for Experimental Surgery and Anesthesiology, Katholieke Universiteit Leuven, Belgium
    FASEB J 15:2073-84. 2001
    ..Both enzymes actively protect hypercholesterolemic mice against atherosclerosis. Oxidized LDL inhibits these enzymes. Thus, oxidized LDL and HDL are indeed antagonists in the development of cardiovascular disease...
  7. ncbi Structure-reactivity studies of serum paraoxonase PON1 suggest that its native activity is lactonase
    Olga Khersonsky
    Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel
    Biochemistry 44:6371-82. 2005
    ..These, and the relatively high rates measured with several lactone substrates (k(cat)/K(M) approximately 10(6) M(-)(1) s(-)(1)) imply that PON1 is in fact a lactonase...
  8. doi Immunohistochemical analysis of paraoxonases-1 and 3 in human atheromatous plaques
    Judit Marsillach
    Centre de Recerca Biomedica, Hospital Universitari de Sant Joan, Institut d Investigacions Sanitaries Pere Virgili, Universitat Rovira i Virgili, Reus, Catalunya, Spain
    Eur J Clin Invest 41:308-14. 2011
    ..The paraoxonase (PON) enzyme family comprising PON1, PON2 and PON3 are antioxidant enzymes that degrade bioactive oxidised lipids and are thus antiatherogenic...
  9. ncbi Modulation of paraoxonase (PON1) activity
    Lucio G Costa
    Department of Environmental and Occupational Health Sciences, University of Washington, 4225 Roosevelt Way NE, Suite 100, Seattle, WA 98105, USA
    Biochem Pharmacol 69:541-50. 2005
    ....
  10. doi The three-gene paraoxonase family: physiologic roles, actions and regulation
    Louis Philippe Precourt
    Research Centre, CHU Sainte Justine, Department of Nutrition, Universite de Montreal, Montreal, Quebec, Canada
    Atherosclerosis 214:20-36. 2011
    ....
  11. pmc Pharmacological and dietary modulators of paraoxonase 1 (PON1) activity and expression: the hunt goes on
    Lucio G Costa
    Dept of Environmental and Occupational Health Sciences, University of Washington, 4225 Roosevelt Way NE, Seattle, WA 98105, USA
    Biochem Pharmacol 81:337-44. 2011
    ....
  12. ncbi The human serum paraoxonase/arylesterase gene (PON1) is one member of a multigene family
    S L Primo-Parmo
    Department of Anesthesiology, University of Michigan Medical School, R5036 Kresge II Building, Ann Arbor, Michigan, 48109 0572, USA
    Genomics 33:498-507. 1996
    ..The expanded number of PON genes will have important implications for future experiments designed to discover the individual functions, catalytic properties, and physiological roles of the paraoxonases...
  13. pmc Relationship of paraoxonase 1 (PON1) gene polymorphisms and functional activity with systemic oxidative stress and cardiovascular risk
    Tamali Bhattacharyya
    Department of Cell Biology, Cleveland Clinic, Cleveland, Ohio 44195, USA
    JAMA 299:1265-76. 2008
    ..The relationship between PON1 genotypes and functional activity with systemic measures of oxidative stress and cardiovascular disease (CVD) risk in humans has not been systematically investigated...
  14. ncbi Low paraoxonase activity predicts coronary events in the Caerphilly Prospective Study
    Bharti Mackness
    University Department of Medicine, Manchester Royal Infirmary, University of Manchester, Oxford Rd, Manchester M13 9WL, UK
    Circulation 107:2775-9. 2003
    ..The hypothesis that paraoxonase (PON1) has a role in preventing atherosclerosis is based on experimental, transgenic, and case-control studies but has not previously been tested prospectively...
  15. ncbi Bovine paraoxonase 1 activities in serum and distribution in lipoproteins
    Toru Miyamoto
    Department of Production Disease, National Institute of Animal Health, 3 1 5 Kannondai, Tsukuba, Ibaraki 305 0856, Japan
    J Vet Med Sci 67:243-8. 2005
    ..The different distributions of PON1 among HDL subpopulations might be concerned to the function and metabolism of bovine HDL...
  16. doi Discordance in human paraoxonase-1 gene between phenotypes and genotypes in chronic kidney disease
    Gyorgy Paragh
    1st Department of Medicine, Faculty of Public Health, University of Debrecen, Debrecen, Hungary
    Nephron Clin Pract 113:c46-53. 2009
    ..Moreover, significantly reduced PON1 activity was found in chronic kidney disease (CKD) and renal transplant patients...
  17. doi The role of paraoxonase 1 in the detoxification of homocysteine thiolactone
    Hieronim Jakubowski
    Department of Biochemistry and Biotechnology, University of Life Sciences, Poznan, Poland
    Adv Exp Med Biol 660:113-27. 2010
    ..This article outlines Hcy-thiolactone pathobiology and reviews evidence documenting the role of PON1 in minimizing Hcy-thiolactone and N-Hcy-protein accumulation...
  18. doi Serum paraoxonase 1 (PON1) lactonase activity is lower in end-stage renal disease patients than in healthy control subjects and increases after hemodialysis
    Alejandro Gugliucci
    Glycation, Oxidation and Disease Laboratory, Division of Basic Medical Sciences, Touro University California, Mare Island, Vallejo, CA 94592, USA
    Clin Chem Lab Med 49:61-7. 2011
    ..The mechanism of paraoxonase 1 (PON1) atheroprotective remains elusive. The lactonizing/lactonase activity of PON1 is gaining favor as the most significant in physiology...
  19. ncbi Paraoxonase 1 arylesterase activity and mass are reduced and inversely related to C-reactive protein in patients on either standard or home nocturnal hemodialysis
    J Kannampuzha
    Keenan Research Center, Li Ka Shing Knowledge Institute, Ontario, Canada
    Clin Nephrol 73:131-8. 2010
    ..We determined serum PON1 mass and arylesterase activities in a group of HNHD patients and compared them to SHD patients and a group of healthy controls (HC)...
  20. pmc Paraoxonase 1 (PON1) gene variants are not associated with clopidogrel response
    J P Lewis
    Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, Maryland, USA
    Clin Pharmacol Ther 90:568-74. 2011
    ..01, P = 0.78). None of 49 additional PON1 variants evaluated was associated with post-clopidogrel platelet aggregation. These findings do not support a role for PON1 as a determinant of clopidogrel response...
  21. ncbi Human and murine paraoxonase 1 are host modulators of Pseudomonas aeruginosa quorum-sensing
    Egon A Ozer
    Department of Internal Medicine Roy J and Lucille A Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
    FEMS Microbiol Lett 253:29-37. 2005
    ..Thus, paraoxonase interruption of bacterial communication represents a novel mechanism to modulate quorum-sensing by bacteria. The consequences for host immunity are yet to be determined...
  22. doi Paraoxonase 2 is down-regulated by the Pseudomonas aeruginosa quorumsensing signal N-(3-oxododecanoyl)-L-homoserine lactone and attenuates oxidative stress induced by pyocyanin
    Sven Horke
    Department of Pharmacology, University Medicine Mainz, Obere Zahlbacher Strasse 67, 55131 Mainz, Germany
    Biochem J 426:73-83. 2010
    ..These findings support a key role for PON2 in the defence against Ps. aeruginosa virulence, but also reveal a mechanism by which the bacterium may subvert the protection afforded by PON2...
  23. ncbi Functional genomic of the paraoxonase (PON1) polymorphisms: effects on pesticide sensitivity, cardiovascular disease, and drug metabolism
    Lucio G Costa
    Department of Environmental Health, University of Washington, Seattle, Washington 98195, USA
    Annu Rev Med 54:371-92. 2003
    ..A more recent area of investigation, the role of PON1 in drug metabolism, is also discussed. We emphasize the importance of considering both PON1 isoforms and PON1 levels in disease/sensitivity association studies...
  24. ncbi Opposite regulation of the human paraoxonase-1 gene PON-1 by fenofibrate and statins
    Cédric Gouédard
    Institut National de la Santé et de la Recherche Médicale Unité 490, Centre Universitaire des Saints Peres, Paris, France
    Mol Pharmacol 63:945-56. 2003
    ..Regarding the toxicological aspects, the induction achieved with fenofibric acid, although limited, could increase organophosphate metabolism and may be relevant in certain conditions for protective treatments...
  25. ncbi Paraoxonase (PON1) deficiency is associated with increased macrophage oxidative stress: studies in PON1-knockout mice
    Orit Rozenberg
    Lipid Research Laboratory, Department of Anatomy and Cell Biology, The Technion Faculty of Medicine, The Rappaport Family Institute for Research in the Medical Sciences and Rambam Medical Center, Haifa, Israel
    Free Radic Biol Med 34:774-84. 2003
    ....
  26. ncbi Human serum paraoxonase (PON 1) is inactivated by oxidized low density lipoprotein and preserved by antioxidants
    M Aviram
    The Lipid Research Laboratory, Technion Faculty of Medicine, The Rappaport Family Institute for Research in the Medical Sciences and Rambam Medical Center, Haifa, Israel
    Free Radic Biol Med 26:892-904. 1999
    ..e. prevention of its formation, and removal of Ox-LDL associated oxidized lipids which are generated during LDL oxidation...
  27. ncbi Paraoxonase activity in high-density lipoproteins: a comparison between healthy and obese females
    G Ferretti
    Istituto di Biochimica, Facolta di Medicina e Chirurgia, Universita Politecnica delle Marche, Via Ranieri, 60131 Ancona, Italy
    J Clin Endocrinol Metab 90:1728-33. 2005
    ..The lower paraoxonase activity and the compositional changes in HDL and LDL could contribute to the greater risk of cardiovascular disease associated with obesity...
  28. doi Anti-inflammatory properties of paraoxonase-1 in atherosclerosis
    Bharti Mackness
    Universitat Rovari i Virgili, Center de Recerca Biomedica Hospital Universitari de Sant Joan, 43201, Reus, Spain
    Adv Exp Med Biol 660:143-51. 2010
    ....
  29. doi No association of paraoxonase-1 Q192R genotypes with platelet response to clopidogrel and risk of stent thrombosis after coronary stenting
    Dirk Sibbing
    Deutsches Herzzentrum München and 1 Medizinische Klinik, Klinikum rechts der Isar, Technische Universitat Munchen, Lazarettstrasse 36, Munich, Germany
    Eur Heart J 32:1605-13. 2011
    ..The aim of this study was to assess the impact of the PON1 Q192R genotype in parallel to that of CYP2C19*2 on the antiplatelet effect of clopidogrel and the risk of ST in clopidogrel-treated patients...
  30. pmc Paraoxonase 1 polymorphisms and ischemic stroke risk: A systematic review and meta-analysis
    Issa J Dahabreh
    Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Boston, Massachusetts, USA
    Genet Med 12:606-15. 2010
    ..We performed a meta-analysis of published studies investigating the association between ischemic stroke and two nonsynonymous PON1 polymorphisms, rs662 (p.Q192R) and rs854560 (p.L55M) in humans...
  31. ncbi The 'evolvability' of promiscuous protein functions
    Amir Aharoni
    Department of Biological Chemistry, The Weizmann Institute of Science, Rehovot 76100, Israel
    Nat Genet 37:73-6. 2005
    ..Thus, an evolving protein can initially acquire increased fitness for a new function without losing its original function. Gene duplication and the divergence of a completely new protein may then follow...
  32. ncbi Paraoxonase-2 reduces oxidative stress in vascular cells and decreases endoplasmic reticulum stress-induced caspase activation
    Sven Horke
    Department of Pharmacology, Johannes Gutenberg University, Obere Zahlbacher Strasse 67, 55131 Mainz, Germany
    Circulation 115:2055-64. 2007
    ..Here, we analyzed the ROS-reducing capability of paraoxonase-2 (PON2) in different vascular cells and its involvement in the endoplasmic reticulum stress pathway known as the unfolded protein response...
  33. ncbi Human serum paraoxonases (PON1) Q and R selectively decrease lipid peroxides in human coronary and carotid atherosclerotic lesions: PON1 esterase and peroxidase-like activities
    M Aviram
    Lipid Research Laboratory, Technion Faculty of Medicine, The Rappaport Family Institute for Research in the Medical Sciences, Rambam Medical Center, Haifa, Israel
    Circulation 101:2510-7. 2000
    ..PON1 protects LDL from oxidation, and during LDL oxidation, PON1 is inactivated...
  34. ncbi Paraoxonase-2 deficiency enhances Pseudomonas aeruginosa quorum sensing in murine tracheal epithelia
    David A Stoltz
    Department of Internal Medicine, Roy J and Lucille A Carver College of Medicine, University of Iowa, 440 EMRB, Iowa City, IA 52242, USA
    Am J Physiol Lung Cell Mol Physiol 292:L852-60. 2007
    ..In summary, these results show that loss of PON2 impairs 3OC12-HSL degradation by airway epithelial cells and suggests that diffusion of 3OC12-HSL into the airway cells can be the rate-limiting step for degradation of the molecule...
  35. ncbi The 192R/Q polymorphs of serum paraoxonase PON1 differ in HDL binding, lipolactonase stimulation, and cholesterol efflux
    Leonid Gaidukov
    Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, Israel
    J Lipid Res 47:2492-502. 2006
    ....
  36. ncbi Dietary determinants of serum paraoxonase activity in healthy humans
    Paivi Kleemola
    Department of Applied Chemistry and Microbiology Nutrition, University of Helsinki, PO Box 27, FW 00014 Helsinki, Finland
    Atherosclerosis 160:425-32. 2002
    ..Malondialdehyde levels showed conflicting associations with diet. The results suggest that the significantly lower PON activity associated with high vegetable intake needs to be studied further...
  37. doi Paraoxonase 1 (PON1) status in gastroesophageal malignancies and associated paraneoplastic syndromes - connection with inflammation
    Malgorzata Krzystek-Korpacka
    Department of Medical Biochemistry, Wroclaw Medical University, Wroclaw, Poland
    Clin Biochem 41:804-11. 2008
    ..To evaluate the status and diagnostic utility of antioxidant paraoxonase 1 (PON1) in gastroesophageal cancers...
  38. ncbi Butyrylcholinesterase, paraoxonase, and albumin esterase, but not carboxylesterase, are present in human plasma
    Bin Li
    University of Nebraska Medical Center, Eppley Institute, Omaha, NE 68198 6805, USA
    Biochem Pharmacol 70:1673-84. 2005
    ..Since human plasma contains no carboxylesterase, only BChE, PON1, and albumin esterases need to be considered when evaluating hydrolysis of an ester drug in human plasma...
  39. ncbi Leptin decreases plasma paraoxonase 1 (PON1) activity and induces oxidative stress: the possible novel mechanism for proatherogenic effect of chronic hyperleptinemia
    Jerzy Bełtowski
    Department of Pathophysiology, Medical University, ul Jaczewskiego 8, 20 090 Lublin, Poland
    Atherosclerosis 170:21-9. 2003
    ..These mechanisms may be involved in atherogenesis in hyperleptinemic obese individuals...
  40. doi Circulating endothelial cells are elevated in patients with type 1 diabetes mellitus
    Ebru Asicioglu
    Division of Nephrology, Department of Internal Medicine, Marmara University School of Medicine, Tophanelioglu Caddesi, No 15 10, Altunizade, Uskudar, Istanbul 32622, Turkey
    Eur J Endocrinol 162:711-7. 2010
    ..Since type 1 diabetes is associated with vascular damage, we hypothesized high CEC numbers in this patient population...
  41. pmc New markers of early cardiovascular risk in multiple sclerosis patients: oxidized-LDL correlates with clinical staging
    Filipe Palavra
    Neurology Department, General Hospital, University and Hospital Centre of Coimbra, Coimbra, Portugal
    Dis Markers 34:341-8. 2013
    ....
  42. doi Oxidative inactivation of lactonase activity of purified human paraoxonase 1 (PON1)
    Su Duy Nguyen
    Laboratory of Lipid Biochemistry and Protein Interactions, Department of Molecular Cell Biology, KU Leuven, Herestraat 49, 3000 Leuven, Belgium
    Biochim Biophys Acta 1790:155-60. 2009
    ..In addition, we have showed that radical-induced inactivation of lactonase activity is prevented by some lipids...
  43. doi CYP2C19 but not PON1 genetic variants influence clopidogrel pharmacokinetics, pharmacodynamics, and clinical efficacy in post-myocardial infarction patients
    Jean Sebastien Hulot
    Universite Pierre et Marie Curie Paris 6, INSERM UMR S 956, Pharmacology Department, Pitie Salpetriere University Hospital, Paris, France
    Circ Cardiovasc Interv 4:422-8. 2011
    ..We tested the effects of PON1 polymorphisms on clopidogrel pharmacokinetics and pharmacodynamics and the occurrence of cardiovascular outcomes in young post-myocardial infarction (MI) patients treated with clopidogrel...
  44. doi HDL-paraoxonase and membrane lipid peroxidation: a comparison between healthy and obese subjects
    Gianna Ferretti
    Department of Biochemistry, Biology and Genetics, Marche Polytechnic University, Ancona, Italy
    Obesity (Silver Spring) 18:1079-84. 2010
    ..In conclusion, the decrease of HDL-PON activity and the lower HDL protective action against membrane peroxidation in obese patients could contribute to accelerate the cellular oxidative damage and arteriosclerosis in obesity...
  45. doi Paraoxonase-1 status in Crohn's disease and ulcerative colitis
    Dorota Boehm
    Department of Medical Biochemistry, Wroclaw Medical University, Wroclaw, Poland
    Inflamm Bowel Dis 15:93-9. 2009
    ..Paraoxonase 1 (PON1) is an extracellular enzyme, which in the gastrointestinal tract may act as a local detoxifier, antioxidant, immunomodulator, and/or quorum-quenching factor. There are no data on PON1 activity in Crohn's disease (CD)...
  46. doi PON1 and oxidative stress in human sepsis and an animal model of sepsis
    Dragomir Draganov
    Head of Toxicokinetics, Metabolism Department, WIL Research Laboratories, LLC, Ashland, OH 44805, USA
    Adv Exp Med Biol 660:89-97. 2010
    ..Persistently low PON1 activity in plasma was associated with lethal outcome in human and murine sepsis...
  47. doi Modulation of paraoxonase 1 and protein N-homocysteinylation by leptin and the synthetic liver X receptor agonist T0901317 in the rat
    Jerzy Beltowski
    Department of Pathophysiology, Medical University, 20 090 Lublin, Poland
    J Endocrinol 204:191-8. 2010
    ..LXR agonists normalize Hcy-thiolactonase levels and decrease protein N-homocysteinylation, especially under conditions associated with excess leptin such as metabolic syndrome...
  48. doi Effect of homocysteinylation on high density lipoprotein physico-chemical properties
    Gianna Ferretti
    Dipartimento di Biochimica, Biologia e Genetica, Universita Politecnica delle Marche, Via Ranieri, 60131 Ancona, Italy
    Chem Phys Lipids 163:228-35. 2010
    ....
  49. pmc Human PON1, a biomarker of risk of disease and exposure
    C E Furlong
    University of Washington, Department of Medicine Div of Medical Genetics, Seattle, WA, United States
    Chem Biol Interact 187:355-61. 2010
    ..Immunolocalization studies of PONs 1, 2 and 3 in nearly all mouse tissues suggest that the functions of PONs 1 and 3 extend beyond the plasma and the HDL particle...
  50. ncbi Prenatal pesticide and PCB exposures and birth outcomes
    Mary S Wolff
    Department of Community and Preventive Medicine, Mount Sinai School of Medicine, New York, New York 10029, USA
    Pediatr Res 61:243-50. 2007
    ..In summary, we found suggestive relationships between prenatal environmental biomarkers and birth outcomes in this population. Maternal susceptibility factors including PON1 and maternal weight contributed to the observed effects...
  51. pmc Paraoxonase 2 attenuates macrophage triglyceride accumulation via inhibition of diacylglycerol acyltransferase 1
    Mira Rosenblat
    Lipid Research Laboratory, Technion Faculty of Medicine, Rappaport Family Institute for Research in the Medical Sciences, Rambam Medical Center, Haifa, Israel
    J Lipid Res 50:870-9. 2009
    ..We thus conclude that PON2 attenuates macrophage triglyceride accumulation and foam cell formation via inhibition of microsomal DGAT1 activity, which appears to be sensitive to oxidative state...
  52. ncbi Acetylcholinesterase/paraoxonase interactions increase the risk of insecticide-induced Parkinson's disease
    Liat BenMoyal-Segal
    The Life Sciences Institute, The Hebrew University of Jerusalem, Israel
    FASEB J 19:452-4. 2005
    ..Our findings suggest that inherited interactive weakness of AChE and PON1 expression increases the insecticide-induced occurrence of Parkinson's disease...
  53. doi Paraoxonase 1 (PON1) inhibits monocyte-to-macrophage differentiation
    Mira Rosenblat
    The Lipid Research Laboratory, Technion Faculty of Medicine, The Rappaport Family Institute for Research in the Medical Sciences, Rambam Medical Center, Haifa, Israel
    Atherosclerosis 219:49-56. 2011
    ..To analyze paraoxonase 1 (PON1) effect on monocyte-to-macrophage differentiation...
  54. doi Paraoxonase 1, quorum sensing, and P. aeruginosa infection: a novel model
    M L Estin
    Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA
    Adv Exp Med Biol 660:183-93. 2010
    ..This work demonstrates the value of a D. melanogaster model for investigating the specific functions of members of the paraoxonase family in vivo, and suggests that PON1 plays a role in innate immunity...
  55. pmc Diminished antioxidant activity of high-density lipoprotein-associated proteins in systolic heart failure
    W H Wilson Tang
    Center for Cardiovascular Diagnostics and Prevention, Department of Cell Biology, Lerner Research Institute, The Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA
    Circ Heart Fail 4:59-64. 2011
    ..In the present study, we sought to determine the prognostic role of serum arylesterase activity in subjects with systolic heart failure, particularly in relation to established cardiac biomarkers...
  56. ncbi The importance of high-density lipoproteins for paraoxonase-1 secretion, stability, and activity
    Richard W James
    Clinical Diabetes Unit, Division of Endocrinology, Diabetes, and Nutrition, Faculty of Medicine, University Hospital, 24 Rue Micheli du Crest, 1211 Geneva 14, Switzerland
    Free Radic Biol Med 37:1986-94. 2004
    ..Finally, we highlight questions concerning the HDL-PON1 association that remain unanswered but are of particular importance in defining PON1 efficiency...
  57. pmc Association of organophosphate pesticide exposure and paraoxonase with birth outcome in Mexican-American women
    Kim G Harley
    Center for Environmental Research and Children s Health, School of Public Health, University of California, Berkeley, California, United States of America
    PLoS ONE 6:e23923. 2011
    ..We explored whether paraoxonase (PON1), a key enzyme involved in detoxification of OPs, could be an effect modifier in this association...
  58. pmc The roles of PON1 and PON2 in cardiovascular disease and innate immunity
    Diana M Shih
    Division of Cardiology, Department of Medicine, University of California, Los Angeles, California 90095 1679, USA
    Curr Opin Lipidol 20:288-92. 2009
    ..In this review, we summarize studies published within the last year, elucidating involvement of PON1 and PON2 in oxidative stress, CVD, and innate immune responses...
  59. ncbi Adenovirus mediated expression of human paraoxonase 2 protects against the development of atherosclerosis in apolipoprotein E-deficient mice
    Carey J Ng
    Atherosclerosis Research Unit, Division of Cardiology, Department of Medicine, 47 123 CHS, Los Angeles, CA 90095, USA
    Mol Genet Metab 89:368-73. 2006
    ....
  60. ncbi Genetic variation in the paraoxonase-3 (PON3) gene is associated with serum PON1 activity
    Dharambir K Sanghera
    Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA
    Ann Hum Genet 72:72-81. 2008
    ..To our knowledge, this is the first study reporting the association of the PON3 gene variants with PON1 activity...
  61. pmc The Gln-Arg191 polymorphism of the human paraoxonase gene (HUMPONA) is not associated with the risk of coronary artery disease in Finns
    M Antikainen
    National Public Health Institute, Department of Biochemistry, Helsinki, Finland
    J Clin Invest 98:883-5. 1996
    ..In conclusion, we found no association between the Gln-Arg 191 polymorphism of the human paraoxonase gene and coronary artery disease in Finns...
  62. doi Maternal exposure to floricultural work during pregnancy, PON1 Q192R polymorphisms and the risk of low birth weight
    G Moreno-Banda
    Population Health Research Center, National Institute of Public Health, Avenida Universidad 655, Colonia Santa Maria Ahuacatitlan, 62508 Cuernavaca, Morelos, Mexico
    Sci Total Environ 407:5478-85. 2009
    ..Paraoxonase (PON1) detoxifies organophosphates by cleavage of active oxons. Some PON1 gene polymorphisms could reduce the enzyme activity and increase susceptibility to OP toxicity...
  63. pmc Drosophila are protected from Pseudomonas aeruginosa lethality by transgenic expression of paraoxonase-1
    David A Stoltz
    Department of Internal Medicine, University of Iowa, Carver College of Medicine, Iowa City, Iowa 52242, USA
    J Clin Invest 118:3123-31. 2008
    ....
  64. pmc One enzyme, two functions: PON2 prevents mitochondrial superoxide formation and apoptosis independent from its lactonase activity
    Sebastian Altenhöfer
    Department of Pharmacology, University Medical Center, Johannes Gutenberg University, Obere Zahlbacher Strasse 67, 55131 Mainz, Germany
    J Biol Chem 285:24398-403. 2010
    ..Collectively, our study provides detailed mechanistic insight into the functions of PON2, which is important for its role in innate immunity, atherosclerosis, and cancer...
  65. doi Studies on protective effects of human paraoxonases 1 and 3 on atherosclerosis in apolipoprotein E knockout mice
    C Zhang
    State Key Laboratory of Pharmaceutical Biotechnology, Life Science School, Nanjing University, Nanjing, PR China
    Gene Ther 17:626-33. 2010
    ..In conclusion, hPON1 and hPON3 exhibited similar potentials in reducing arterial lesion size, but they exerted antiatherogenic effects in distinct ways...
  66. doi Relation of PON1 and CYP1A1 genetic polymorphisms to clinical findings in a cross-sectional study of a Greek rural population professionally exposed to pesticides
    A M Tsatsakis
    Centre of Toxicology Sciences and Research, Medical School, University of Crete, Heraklion, Crete, Greece, Voutes, Heraklion, 71409 Crete, Greece
    Toxicol Lett 186:66-72. 2009
    ....
  67. ncbi Calcium-dependent human serum homocysteine thiolactone hydrolase. A protective mechanism against protein N-homocysteinylation
    H Jakubowski
    Department of Microbiology and Molecular Genetics, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, New Jersey 07103, USA
    J Biol Chem 275:3957-62. 2000
    ..By detoxifying homocysteine thiolactone, the thiolactonase/paraoxonase would protect proteins against homocysteinylation, a potential contributing factor to atherosclerosis...
  68. doi Association of paraoxonase gene cluster polymorphisms with ALS in France, Quebec, and Sweden
    P N Valdmanis
    Center of Excellence in Neuromics, University of Montreal, CHUM Research Center, Notre Dame Hospital, Montreal, Quebec, Canada
    Neurology 71:514-20. 2008
    ..In addition, PON variants were shown to be associated with susceptibility to ALS in several North American and European populations...
  69. doi HDL-associated paraoxonase-1 can redistribute to cell membranes and influence sensitivity to oxidative stress
    Sara P Deakin
    Clinical Diabetes Unit, Department of Internal Medicine, University of Geneva, 1211 Geneva 4, Switzerland
    Free Radic Biol Med 50:102-9. 2011
    ..The observations may be of relevance to tissues exposed to oxidative stress and/or bacterial infection...
  70. ncbi The role of paraoxonase 1 activity in cardiovascular disease: potential for therapeutic intervention
    Michael I Mackness
    University Department of Medicine, Manchester Royal Infirmary, Manchester, UK
    Am J Cardiovasc Drugs 4:211-7. 2004
    ....
  71. pmc PON1 and neurodevelopment in children from the CHAMACOS study exposed to organophosphate pesticides in utero
    Brenda Eskenazi
    Center for Environmental Research and Children s Health, School of Public Health, University of California, Berkeley, Berkeley, California 94602, USA
    Environ Health Perspect 118:1775-81. 2010
    ....
  72. doi Paraoxonases role in the prevention of cardiovascular diseases
    Mira Rosenblat
    The Lipid Research Laboratory, Technion Faculty of Medicine, The Rappaport Family Institute for Research in the Medical Sciences, Rambam Medical Center, Haifa, Israel
    Biofactors 35:98-104. 2009
    ....
  73. pmc Molecular basis for the polymorphic forms of human serum paraoxonase/arylesterase: glutamine or arginine at position 191, for the respective A or B allozymes
    S Adkins
    Department of Environmental and Industrial Health, School of Public Health, University of Michigan, Ann Arbor 48109 0572
    Am J Hum Genet 52:598-608. 1993
    ..Pedigree analysis showed both polymorphisms to be inherited in the expected Mendelian manner and confirmed that only the 191 polymorphism showed concordance with the serum paraoxonase/arylesterase phenotypes...
  74. pmc Anti-oxidant properties of high-density lipoprotein and atherosclerosis
    Eugene A Podrez
    Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA
    Clin Exp Pharmacol Physiol 37:719-25. 2010
    ..4. The focus of the present review is on the anti-oxidant and anti-inflammatory functions of HDL and its individual components in relation to protection from atherosclerosis...
  75. ncbi The paraoxonase gene family and atherosclerosis
    Carey J Ng
    Atherosclerosis Research Unit, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
    Free Radic Biol Med 38:153-63. 2005
    ....
  76. doi Paraoxonase-1 is a major determinant of clopidogrel efficacy
    Heleen J Bouman
    Department of Cardiology, St Antonius Hospital Nieuwegein, Nieuwegein, The Netherlands
    Nat Med 17:110-6. 2011
    ..Thus, we identified PON1 as a key factor for the bioactivation and clinical activity of clopidogrel. These findings have therapeutic implications and may be exploited to prospectively assess the clinical efficacy of clopidogrel...
  77. ncbi Paraoxonase-2 is a ubiquitously expressed protein with antioxidant properties and is capable of preventing cell-mediated oxidative modification of low density lipoprotein
    C J Ng
    Atherosclerosis Research Unit, University of California, Los Angeles, California 90095 1679, USA
    J Biol Chem 276:44444-9. 2001
    ..However, in contrast to PON1 and PON3, PON2 may exert its antioxidant functions at the cellular level, joining the host of intracellular antioxidant enzymes that protect cells from oxidative stress...
  78. ncbi Human paraoxonases (PON1, PON2, and PON3) are lactonases with overlapping and distinct substrate specificities
    Dragomir I Draganov
    Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
    J Lipid Res 46:1239-47. 2005
    ..None of the recombinant PONs protected low density lipoprotein against copper-induced oxidation in vitro...
  79. ncbi Oxidative inactivation of paraoxonase1, an antioxidant protein and its effect on antioxidant action
    Su Duy Nguyen
    College of Pharmacy, Chungnam National University, Yuseong Ku, Taejon 305 764, South Korea
    Free Radic Res 37:1319-30. 2003
    ....
  80. ncbi Human apolipoprotein A-II enrichment displaces paraoxonase from HDL and impairs its antioxidant properties: a new mechanism linking HDL protein composition and antiatherogenic potential
    Vicent Ribas
    Institut de Recerca de l Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
    Circ Res 95:789-97. 2004
    ..Further, the displacement of PON1 by apoA-II could explain in part why PON1 is mostly found in HDL particles with apoA-I and without apoA-II, as well as the poor antiatherogenic properties of apoA-II-rich HDL...
  81. ncbi Combined serum paraoxonase knockout/apolipoprotein E knockout mice exhibit increased lipoprotein oxidation and atherosclerosis
    D M Shih
    Division of Cardiology, Department of Medicine, UCLA, Los Angeles, California 90095, USA
    J Biol Chem 275:17527-35. 2000
    ..These data demonstrate that PON1 deficiency promotes LDL oxidation and atherogenesis in apoE KO mice...
  82. ncbi Paraoxonase 1 (PON1) is present in postprandial chylomicrons
    Bianca Fuhrman
    The Lipid Research Laboratory, Technion Faculty of Medicine, The Rappaport Family Institute for Research in the Medical Sciences and Rambam Medical Center, Haifa 31096, Israel
    Atherosclerosis 180:55-61. 2005
    ..We conclude that postprandial chylomicrons contain PON1, which may function in the removal of atherogenic oxidized lipids...
  83. doi Immunohistochemical analysis of paraoxonases-1, 2, and 3 expression in normal mouse tissues
    Judit Marsillach
    Centre de Recerca Biomedica, Hospital Universitari de Sant Joan, Institut d Investigacions Sanitaries Pere Virgili, Universitat Rovira i Virgili, Reus, Spain
    Free Radic Biol Med 45:146-57. 2008
    ..This study provides an experimental model to investigate the role played by these enzymes as antioxidants and their relationship with the development of a variety of diseases...
  84. ncbi Paraoxonase gene variants are associated with autism in North America, but not in Italy: possible regional specificity in gene-environment interactions
    M D'Amelio
    Laboratory of Molecular Psychiatry and Neurogenetics, University Campus Bio Medico, Rome, Italy
    Mol Psychiatry 10:1006-16. 2005
    ....
  85. pmc Dominant role of paraoxonases in inactivation of the Pseudomonas aeruginosa quorum-sensing signal N-(3-oxododecanoyl)-L-homoserine lactone
    John F Teiber
    The University of Texas Southwestern Medical Center, Department of Internal Medicine, Division of Epidemiology, 5323 Harry Hines Blvd, Dallas, TX 75390 8874, USA
    Infect Immun 76:2512-9. 2008
    ..These findings suggest that PONs, particularly PON2, could be an important mechanism by which 3OC12-HSL is inactivated in mammals...
  86. pmc Paraoxonase-1 promoter haplotypes and serum paraoxonase: a predominant role for polymorphic position - 107, implicating the Sp1 transcription factor
    Sara Deakin
    Clinical Diabetes Unit, Division of Endocrinology and Diabetology, Medical Faculty, University Hospital, 1211 Geneva 14, Switzerland
    Biochem J 372:643-9. 2003
    ..A potential role for the transcription factor Sp1 has been demonstrated, which is consistent with the disruption of an Sp1 recognition sequence by the -107 polymorphism...
  87. ncbi Assessment of serum paraoxonase and arylesterase activity in patients with endometrial cancer
    D T Arioz
    Department of Obstetrics and Gynecology, Faculty of Medicine, Afyonkarahisar Kocatepe University, Afyonkarahisar, Turkey
    Eur J Gynaecol Oncol 30:679-82. 2009
    ..The aim of this study was to compare the serum levels of paraoxonase and arylesterase activity in patients with endometrial cancer to those of healthy controls...
  88. ncbi Distribution spectrum of paraoxonase activity in HDL fractions
    Christoph Bergmeier
    Labor für angewandte Biochemie, Gustav Embden Zentrum für Biologische Chemie, Klinikum der J W Goethe Universitat, Frankfurt Main, Germany
    Clin Chem 50:2309-15. 2004
    ..However, because HDL is not a homogeneous fraction, it is important to investigate in which subgroups of HDL active PON1 is located. It would also be useful to determine density profiles of the HDL apolipoproteins (Apo) E and J...
  89. ncbi Paraoxonase Gln-Arg(192) and Leu-Met(55) gene polymorphisms and enzyme activity in a population with a low rate of coronary heart disease
    Natalia Ferre
    Centre de Recerca Biomedica, Hospital Universitari de Sant Joan, Reus, Spain
    Clin Biochem 35:197-203. 2002
    ..To assess whether paraoxonase (PON1) polymorphisms at positions 55 and 192 and/or their phenotypic expressions influence the risk of myocardial infarction (MI) in Spanish population...
  90. doi Effect of paraoxonase-1 polymorphism on clinical outcomes in patients treated with clopidogrel after an acute myocardial infarction
    T Simon
    Assistance Publique Hopitaux de Paris APHP, Hopital St Antoine, URC EST, Paris, France
    Clin Pharmacol Ther 90:561-7. 2011
    ..87, 95% CI 2.52-18.72 and adjusted HR 3.06, 95% CI 1.47-6.41). Unlike CYP2C19 polymorphism, PON1 (Q192R) polymorphism is not a major pharmacogenetic contributor of clinical response to clopidogrel in AMI patients...
  91. doi Four genetic polymorphisms of paraoxonase gene and risk of coronary heart disease: a meta-analysis based on 88 case-control studies
    Mingsong Wang
    Department of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai 200433, China
    Atherosclerosis 214:377-85. 2011
    ..Many studies have examined the association between polymorphisms in the PON gene and risk of coronary heart disease (CHD), but the results have been inconsistent...
  92. ncbi Serum paraoxonase levels in gastric cancer
    M N Akçay
    Ataturk University Medical Faculty, Department of General Surgery, Erzurum, Turkey
    Hepatogastroenterology 50:cclxxiii-cclxxv. 2003
    ..So, we intended to measure serum PON, HDL, LDL and very low-density lipoprotein (VLDL) levels and to investigate the relation of serum PON to plasma lipoproteins in the patients with gastric cancer...
  93. ncbi Chromogenic and fluorogenic assays for the lactonase activity of serum paraoxonases
    Olga Khersonsky
    Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel
    Chembiochem 7:49-53. 2006
  94. doi Paraoxonase 1 protects against protein N-homocysteinylation in humans
    Joanna Perla-Kajan
    Department of Microbiology and Molecular Genetics, UMDNJ New Jersey Medical School, International Center for Public Health, 225 Warren St Newark, NJ 07101 1709, USA
    FASEB J 24:931-6. 2010
    ..Perła-Kaján, J., Jakubowski, H. Paraoxonase 1 protects against protein N-homocysteinylation in humans...
  95. ncbi Role of paraoxonase (PON1) status in pesticide sensitivity: genetic and temporal determinants
    Clement E Furlong
    Genome Sciences and Medicine, Division of Medical Genetics, University of Washington, Box 357720, Seattle, WA 98195 7720, USA
    Neurotoxicology 26:651-9. 2005
    ..Our studies indicate that children less than 2 years old, especially those homozygous for PON1Q192, would be predicted to be particularly susceptible to CPO toxicity...
  96. ncbi Impaired high density lipoprotein antioxidant activity in healthy postmenopausal women
    Valeria Zago
    Laboratory of Lipids and Lipoproteins, Departament of Clinical Biochemistry, School of Pharmacy and Biochemistry, University of Buenos Aires, Junin 956 C1113AAD, Buenos Aires, Argentina
    Atherosclerosis 177:203-10. 2004
    ..In turn, this was related to triglyceride enrichment of HDL particles. All these alterations were independent from HDL cholesterol plasma levels...
  97. pmc Markers of increased cardiovascular risk in postmenopausal women: focus on oxidized-LDL and HDL subpopulations
    Filipa Mascarenhas-Melo
    Laboratory of Pharmacology and Experimental Therapeutics, IBILI, Faculty of Medicine, University of Coimbra, 3000 548 Coimbra, Portugal
    Dis Markers 35:85-96. 2013
    ..To evaluate the effect of gender and menopause in cardiovascular risk (CVR) in a healthy population based on both classical and nontraditional markers...
  98. ncbi Proinflammatory cytokines but not acute phase serum amyloid A or C-reactive protein, downregulate paraoxonase 1 (PON1) expression by HepG2 cells
    Yoshitaka Kumon
    Second Department of Internal Medicine, Kochi Medical School, Nankoku, Japan
    Amyloid 9:160-4. 2002
    ..These findings suggested that the decrease in serum PON activity after abdominal surgery in our previous clinical study may be ascribed to a decrease in steady state PON1 mRNA expression by liver with proinflammatory cytokines...
  99. ncbi Paraoxonase 2 (PON2) expression is upregulated via a reduced-nicotinamide-adenine-dinucleotide-phosphate (NADPH)-oxidase-dependent mechanism during monocytes differentiation into macrophages
    Maayan Shiner
    Lipid Research Laboratory, Technion Faculty of Medicine, The Rappaport Family Institute for Research in the Medical Sciences and Rambam Medical Center, Haifa 31096, Israel
    Free Radic Biol Med 37:2052-63. 2004
    ..PON2 stimulation may represent a compensatory mechanism against the increase in cellular superoxide anion production and atherogenesis...
  100. ncbi Protective effect of soy isoflavones and activity levels of plasma paraoxonase and arylesterase in the experimental nonalcoholic steatohepatitis model
    Bilal Ustundag
    Department of Biochemistry and Clinical Biochemistry, College of Medicine, Firat Euphrates University, Elazig, Turkey
    Dig Dis Sci 52:2006-14. 2007
    ..They stimulate and increase the activity of the antioxidative paraoxanase enyzme while decreasing the total cholesterol and triglyceride levels...
  101. doi Human paraoxonase-1 activity in childhood obesity and its relation to leptin and adiponectin levels
    Peter Koncsos
    First Department of Medicine, University of Debrecen, Debrecen, Hungary
    Pediatr Res 67:309-13. 2010
    ..Altered levels of leptin, adiponectin and PON1 activities may be useful markers beside the general risk factors in childhood obesity...

Research Grants72

  1. Effect of exposure to organochlorine compounds on the development of obesity and
    GEORGE E HOWELL; Fiscal Year: 2011
    ..This research will determine if exposure to these compounds is a risk factor for development of T2D and if so will provide mechanisms through which these compounds precipitate this disease. ..
  2. RISK FACTORS FOR CVD IN WOMEN
    JOANN ELISABETH MANSON; Fiscal Year: 2012
    ..These promising biochemical and genetic markers may have implications for improving prevention strategies, enhancing treatment options, and generating additional testable hypotheses for heart disease research. ..
  3. Air pollution and the brain: gender as an important determinant of susceptibility
    Lucio G Costa; Fiscal Year: 2013
    ....
  4. Novel mechanisms by which aspirin might protect against atherosclerosis
    Sampath Parthasarathy; Fiscal Year: 2012
    ..In this application, we propose that the actions of aspirin might be mediated by salicylate. We also explore the mechanisms by which PON 1 could be induced by aspirin. ..
  5. Regulation of PTH-induced Osteoanabolism by Inflammatory Lipids
    Yin Tintut; Fiscal Year: 2013
    ..abstract_text> ..
  6. Multicenter ALS Cohort Study of Oxidative Stress and Disease Progression
    Hiroshi Mitsumoto; Fiscal Year: 2013
    ..abstract_text> ..
  7. Biophysics of HDL Dysfunction
    Mary G Sorci-Thomas; Fiscal Year: 2013
    ..Development of these novel assays will make it possible, for the first time, to perform large clinical studies to fully test the idea that dysfunctional HDL is better indicator of atherosclerotic risk. ..
  8. The Rosetta Enzyme ReDesign: Targeting PON1 as OP Scavenger
    Jennifer M Bui; Fiscal Year: 2012
    ..This proposal thus has direct relevance impact in environmental protections and biotechnologies. ..
  9. Pesticides, Paraoxonase and Alzheimer's Disease
    Mark S Kindy; Fiscal Year: 2010
    ..The focus of this proposal is to understand the function of organophosphates (OPs as symbolic ETs) and interrelationship between ETs and paraoxonase (PON- 1) in oxidative stress and inflammation associated with AD. ..
  10. Pc4 PDT for Psoriasis
    Elma D Baron; Fiscal Year: 2011
    ..Our findings may identify the first direct link between psoriasis, inflammation and cardiovascular risk. ..
  11. Center of Catalytic Bioscanvenger Medical Defense Research II: Discovery, Formula
    Dan S Tawfik; Fiscal Year: 2013
    ..In this regard, we will examine the potential of co-administration of conventional therapy with enzymes to protect against GB;synergy may provide unexpectedly high levels of protection against GB. ..
  12. Relationship of Blood Esterases, Pesticide Exposure and Cardiovascular Disease
    Janice Chambers; Fiscal Year: 2009
    ..In addition, we anticipate that we will develop more simplified assay methods for PON1 and CaE that will be more amenable for use as a clinical biomarker. ..
  13. Role of High Density Lipoprotein Particles in amyotrophic lateral sclerosis
    Teepu Siddique; Fiscal Year: 2012
    ..The results from this work will open paths to therapies that seek to rescue potential dysfunctional HDL states found not only in neurodegenerative disease such as ALS but also in more common cardiovascular and metabolic diseases. ..
  14. Moving Beyond HDL Cholesterol, HDL Function as a Coronary Disease Biomarker
    ANAND KUMAR ROHATGI; Fiscal Year: 2013
    ..Helen Hobbs, the Center for Nutrition led by Dr. Scott Grundy, and the Department of Clinical Sciences led by Dr. Milton Packer. ..
  15. Paraoxonase-2 S311C Polymorphism Alters Glycosylation and Lactonase Activity
    David A Stoltz; Fiscal Year: 2011
    ..Findings from the proposed project will hopefully uncover new therapeutic options for P. aeruginosa infections. ..
  16. LIPID PEROXIDATION IN COLORECTAL CANCER
    Manuela Gago Dominguez; Fiscal Year: 2009
    ..4. To conduct a case-case association study to determine if morphological markers of apoptosis in tumor and surrounding free tissue differ among cases with varying exposure levels of a given putative environmental/genetic risk factor. ..
  17. Neurological Outcomes Among Pesticide Applicators
    Fredric Gerr; Fiscal Year: 2009
    ....
  18. Exploring Gene-Environment Factors in Child Brain Tumors
    Beth Mueller; Fiscal Year: 2004
    ..abstract_text> ..
  19. ACTION OF ALCOHOL & QUERCETIN ON ANTI-ATHEROGENIC FACTORS & ATHEROGENESIS
    Raj Lakshman; Fiscal Year: 2007
    ..Therefore, this mechanistic and clinically releyent study on the actions of alcohol/quercetin has the potential to effectively protect against cardiovascular diseases. [unreadable] [unreadable] [unreadable]..
  20. Enzyme Activity Enhancement in Functionalized Nanoporous Support
    Chenghong Lei; Fiscal Year: 2012
    ..abstract_text> ..
  21. PRESERVATION OF HDL FUNCTION DURING EARLY ATHEROGENESIS
    JOHN BIELICKI; Fiscal Year: 2002
    ..Moreover, the research will uncover novel mechanisms for preserving HDL/LCAT function that can be utilized therapeutically to fight the onset of cardiovascular disease. ..
  22. DIET, ENDOTHELIAL FUNCTION AND PEDIATRIC HYPERLIPIDEMIA
    Marguerite Engler; Fiscal Year: 2004
    ..Preventive nursing strategies aimed at early detection of endothelial dysfunction and dietary modification may restore endothelial function in children and adolescents at high risk for CHD. ..
  23. PON1 and Developmental Sensitivity to OP Pesticides
    Nina T Holland; Fiscal Year: 2010
    ..These data will support planning for the National Children's Study, identify subpopulations susceptible to chemical warfare agents, and inform policy decisions for implementation of the Food Quality Protection Act. ..
  24. Genetics of Oxidative Stress in Ventricular Remodeling
    Vasan Ramachandran; Fiscal Year: 2003
    ....
  25. GENETIC EPIDEMIOLOGY OF LIPOPROTEIN/LIPID LEVELS
    M Kamboh; Fiscal Year: 2000
    ....
  26. INTIMAL THICKENING & ANTITOXIDANTS IN HISPANICS & ANGLOS
    James Dwyer; Fiscal Year: 2003
    ..These additional measures, together with those in the original protocol, will allow investigation of relations between longitudinal change in Ath and dietary antioxidants, antioxidant enzymes, and genetic polymorphisms. ..
  27. Targeted Paraoxonase Fusion Protein as a Neurotherapeutic for Nerve Gas Agents
    RUBEN BOADO; Fiscal Year: 2009
    ..The present work will genetically engineer a novel OP hydrolase fusion protein that is able to cross the BBB in humans by receptor-mediated transport. ..
  28. Lipid Regulation of Vascular and Bone Osteoclastogenesis
    Linda Demer; Fiscal Year: 2004
    ....
  29. OXIDATION RISK FACTORS AND IMT PROGESSION IN FH
    Paul Hopkins; Fiscal Year: 2004
    ..Our major hypothesis is that IMT progression will be strongly related to the balance of pro-oxidant and antioxidant factors. The newly added imaging techniques will allow us to compare and contrast results using these endpoints as well. ..
  30. Genetic & Structure-Function Studies: Paraoxonase In SLE
    M Kamboh; Fiscal Year: 2006
    ..We will systematically screen the three PON genes for new mutations (Aim 1) and, in conjunction with known PON potymorphisms, we will evaluate their genetic and functional significances (Aims 2-4). ..
  31. MODERATE ALCOHOL CONSUMPTION AND HDL
    WILLEM DEVILLIERS; Fiscal Year: 2003
    ..This will be done by measuring the bioactivity of paraoxonase and determining the ability of HDL from human subjects exposed to alcohol to protect against macrophage-mediated LDL. ..
  32. GENETICS OF ATHEROSCLEROSIS--ROLE OF INSULIN RESISTANCE
    Willa Hsueh; Fiscal Year: 2003
    ..abstract_text> ..
  33. Atherogenic Effects of Ambient PM In Susceptible Animals
    Andre Nel; Fiscal Year: 2007
    ..These mice will be exposed to CAPs as discussed in Aims 1 and 2, and select endpoints used to demonstrate the effect on atherosclerotic inflammation and apoptosis. ..
  34. Innate Immunity and Bacterial Quorum Sensing
    Hattie Gresham; Fiscal Year: 2009
    ..Understanding the contribution of these innate effectors to quorum quenching and how pathogens avoid it could augment drug design that targets virulence pheromones for inactivation. ..
  35. Prediction and Progression of Carotid Artery Disease
    GAIL JARVIK; Fiscal Year: 2009
    ..Aim 3: Pathway evaluation of oxidative loci and phenotypes in prediction of CAAD. ..
  36. Inflammatory Genomics in Human Carotid Artery Disease
    GAIL JARVIK; Fiscal Year: 2006
    ..Genes that are implicated in disease may eventually allow targeted therapy. ..
  37. Maternal overnutrition and offspring fat mass, metabolic and vascular function.
    Debbie Lawlor; Fiscal Year: 2009
    ....
  38. DEVELOPMENTAL NEUROTOXICITY OF OP INSECTICIDES
    Janice Chambers; Fiscal Year: 2006
    ..abstract_text> ..
  39. Pesticide Toxicity to the Nervous and Endocrine Systems
    Janice Chambers; Fiscal Year: 2006
    ....
  40. Metabolism and Age-Related Organophosphate Toxicity
    Janice Chambers; Fiscal Year: 2005
    ..These results will indicate the contribution of detoxication to toxicity level, and will allow more accurate predictions of age-related differences in toxicity. ..
  41. Identifying targets for diagnosing oral candidiasis
    David Schofield; Fiscal Year: 2005
    ..Since Candida species are the most important fungal pathogen of the oral cavity, the rapid and accurate diagnosis of oral candidiasis using novel disease biomarkers will significantly improve oral health. ..
  42. Folate Polymorphisms, Dietary Folate and Prostate Cancer
    Victoria Stevens; Fiscal Year: 2005
    ..The results of this study are expected to indicate the importance of folate for prostate cancer and whether changing folate consumption can modify the risk associated with genetic variants in the pathway for folate metabolism. ..
  43. Siblings With Ischemic Stroke Study (SWISS)
    JAMES MESCHIA; Fiscal Year: 2009
    ..DNA banking and the creation of permanent lymphoblastoid cell lines will be done to permit future collaborative efforts to study the genetic basis for stroke risk. ..
  44. INNOVATIVE BIOMONITORING FOR LEAD IN SALIVA
    Charles Timchalk; Fiscal Year: 2006
    ..It is reasonable to speculate that once this model system has been adequately validated it can readily be employed to screen sensitive populations (e.g. children) that are at greatest risk from chronic Pb exposure. ..
  45. ISGS: The Ischemic Stroke Genetics Study
    JAMES MESCHIA; Fiscal Year: 2006
    ..The application and SWISS share the same definitions for the present and absence of phenotype and key enrollment criteria. ..
  46. Mixture Modeling: Pesticide Drug Interactions
    Charles Timchalk; Fiscal Year: 2009
    ..It is fully anticipated that this approach will facilitate the understanding of a variety of complex chemical interactions as it relates to the occupational health implications of working with insecticides. ..
  47. Development of Selective Nanoporous Sorbents for Radionuclide Decorporation
    Charles Timchalk; Fiscal Year: 2008
    ..abstract_text> ..
  48. Inflammatory Mechanisms of Atherosclerosis
    Peter Libby; Fiscal Year: 2006
    ..5. We will explore a putative functional role of a novel prostaglandin E2 receptor EP4 interacting protein (EPRAP) in endogenous anti-inflammatory pathways. ..
  49. Coenzyme Q10 in Aging: A Planning Grant
    Beatrice Golomb; Fiscal Year: 2005
    ..Thus there is strong conceptual as well as clinical rationale for assessing whether Q10 provides QOL & functional benefits in aging and whether it protects against untoward events associated with age. ..
  50. Apolipoprotein-mediated cholesterol efflux
    W Davidson; Fiscal Year: 2008
    ..This understanding will form a basis for new interventions designed to enhance apolipoprotein-mediated cholesterol efflux from cells, particularly those within the atherosclerotic vessel wall. ..
  51. BIOLOGY OF PROTEOLYTIC DERIVATIVES OF LP(A)
    ANGELO SCANU; Fiscal Year: 2009
    ..The results of the proposed studies should shed light on whether ox-PL adducts play a role in the cardiovascular pathogenicity of Lp(a). ..
  52. Retrograde Dystrophic Influence of IFN-gamma on Neurons
    Pamela Lein; Fiscal Year: 2006
    ..abstract_text> ..
  53. Light & Heavy Alcohol, Paraoxonase & Oxidized LDL Status
    Raj Lakshman; Fiscal Year: 2008
    ..These investigations are likely to lead to new insights in our understanding of the cardioprotective effects of ligh drinking and proatherogenic effects of heavy drinking both at clinical and at molecular levels. ..
  54. Haplotyping for Environmental Genomics
    James Wetmur; Fiscal Year: 2004
    ....
  55. INTERACTIONS OF LP(A) WITH VASCULAR EXTRACELLULAR MATRIX
    ANGELO SCANU; Fiscal Year: 2002
    ..Underlying these studies is the hypothesis, that the MMP-mediated changes in Lp(a)/apo(a) are favored by the inflammatory milieu of the human atheroma. ..
  56. Extracellular matrix in chloracetanilide carcinogenesis
    Mary Beth Genter; Fiscal Year: 2004
    ..abstract_text> ..
  57. MECHANISMS OF ACTIONS OF ALCOHOL AND OMEGA 3-FATTY ACIDS
    Raj Lakshman; Fiscal Year: 2004
    ....
  58. CONFERENCE ON ARTERIOSCLEROSIS AND VASCULAR BIOLOGY
    Trudy Forte; Fiscal Year: 2004
    ..abstract_text> ..
  59. fMRI Assessment of Organophosphate Neurotoxicity
    Steven Bird; Fiscal Year: 2008
    ..Bird with the facilities, equipment and expertise necessary to achieve the goals set forth in this proposal. ..
  60. ApoA-I Helical Domains and Cardiovascular Aging
    JOHN BIELICKI; Fiscal Year: 2005
    ..These studies are relevant for devising novel strategies to combat cardiovascular aging. ..
  61. PATHOBIOLOGY OF MACROVASCULAR DISEASE IN DIABETES
    Alan Chait; Fiscal Year: 2007
    ..abstract_text> ..
  62. Alcohol-Metabolizing Gene Variation, Lipids, Hemostatic Factors and CVD
    Kelly Volcik; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable] [unreadable]..
  63. Use of an Organophosphorus (OP) Hydrolase for Acute OP Poisoning
    Steven Bird; Fiscal Year: 2008
    ..Our central hypothesis is that OpdA is safe and improves survival after poisoning with parathion. ..
  64. The roles of apolipoprotein A-IV structure and lipid affinity in its function
    W Davidson; Fiscal Year: 2009
    ....
  65. Heavy Drinking & Coronary Disease: Acute/Chronic Effects
    Kenneth Mukamal; Fiscal Year: 2006
    ..These results may prove to have important biological, clinical, and public health implications for the care of CHD. ..
  66. Multi-ethnic Genome-wide Alzheimer association study
    Lindsay A Farrer; Fiscal Year: 2010
    ....
  67. Oxidation Hypothesis--Paradoxes and Pitfalls
    Sampath Parthasarathy; Fiscal Year: 2006
    ..Exercise is also recommended for other diseases such as diabetes and hypertension, diseases in which oxidative stress is also implicated. Thus the outcome of this study will have far reaching implications. ..
  68. PBDEs, DDT and Neurodevelopment in School-Aged Mexican-American Children
    Brenda Eskenazi; Fiscal Year: 2010
    ....