superoxides

Summary

Summary: Highly reactive compounds produced when oxygen is reduced by a single electron. In biological systems, they may be generated during the normal catalytic function of a number of enzymes and during the oxidation of hemoglobin to METHEMOGLOBIN. In living organisms, SUPEROXIDE DISMUTASE protects the cell from the deleterious effects of superoxides.

Top Publications

  1. pmc Mitochondrial formation of reactive oxygen species
    Julio F Turrens
    Department of Biomedical Sciences, University of South Alabama, Mobile, AL 36688, USA
    J Physiol 552:335-44. 2003
  2. pmc How mitochondria produce reactive oxygen species
    Michael P Murphy
    MRC Dunn Human Nutrition Unit, Hills Road, Cambridge CB20XY, UK
    Biochem J 417:1-13. 2009
  3. ncbi Topology of superoxide production from different sites in the mitochondrial electron transport chain
    Julie St-Pierre
    MRC Medical Research Council Dunn Human Nutrition Unit, Hills Road, Cambridge CB2 2XY, England
    J Biol Chem 277:44784-90. 2002
  4. pmc Distinct roles of Nox1 and Nox4 in basal and angiotensin II-stimulated superoxide and hydrogen peroxide production
    Sergey I Dikalov
    Division of Cardiology, Department of Medicine, Emory University School of Medicine, 1639 Pierce Drive, Atlanta, GA 30322, USA
    Free Radic Biol Med 45:1340-51. 2008
  5. pmc Cellular defenses against superoxide and hydrogen peroxide
    James A Imlay
    Department of Microbiology, University of Illinois, Urbana, IL 61801, USA
    Annu Rev Biochem 77:755-76. 2008
  6. ncbi Apocynin is not an inhibitor of vascular NADPH oxidases but an antioxidant
    Sabine Heumüller
    Institut für Kardiovaskuläre Physiologie, Johann Wolfgang Goethe Universitat, Theodor Stern Kai 7, D 60596 Frankfurt am Main, Germany
    Hypertension 51:211-7. 2008
  7. ncbi Superoxide activates mitochondrial uncoupling proteins
    Karim S Echtay
    Medical Research Council Dunn Human Nutrition Unit, Hills Road, Cambridge CB2 2XY, UK
    Nature 415:96-9. 2002
  8. pmc The sites and topology of mitochondrial superoxide production
    Martin D Brand
    Buck Institute for Age Research, 8001 Redwood Blvd, Novato, CA 94945, USA
    Exp Gerontol 45:466-72. 2010
  9. pmc Selective fluorescent imaging of superoxide in vivo using ethidium-based probes
    Kristine M Robinson
    Linus Pauling Institute, Department of Biochemistry and Biophysics, Oregon State University, Corvallis, OR 97331, USA
    Proc Natl Acad Sci U S A 103:15038-43. 2006
  10. ncbi Complex III releases superoxide to both sides of the inner mitochondrial membrane
    Florian L Muller
    Department of Cellular Biology, University of Texas Health Science Center, San Antonio, TX 78284 7762, USA
    J Biol Chem 279:49064-73. 2004

Detail Information

Publications325 found, 100 shown here

  1. pmc Mitochondrial formation of reactive oxygen species
    Julio F Turrens
    Department of Biomedical Sciences, University of South Alabama, Mobile, AL 36688, USA
    J Physiol 552:335-44. 2003
    ..We also discuss various physiological and pathological scenarios resulting from an increased steady state concentration of mitochondrial oxidants...
  2. pmc How mitochondria produce reactive oxygen species
    Michael P Murphy
    MRC Dunn Human Nutrition Unit, Hills Road, Cambridge CB20XY, UK
    Biochem J 417:1-13. 2009
    ....
  3. ncbi Topology of superoxide production from different sites in the mitochondrial electron transport chain
    Julie St-Pierre
    MRC Medical Research Council Dunn Human Nutrition Unit, Hills Road, Cambridge CB2 2XY, England
    J Biol Chem 277:44784-90. 2002
    ..This difference was solely due to an elevated concentration of complex I in rat compared with pigeon heart mitochondria...
  4. pmc Distinct roles of Nox1 and Nox4 in basal and angiotensin II-stimulated superoxide and hydrogen peroxide production
    Sergey I Dikalov
    Division of Cardiology, Department of Medicine, Emory University School of Medicine, 1639 Pierce Drive, Atlanta, GA 30322, USA
    Free Radic Biol Med 45:1340-51. 2008
    ..These findings also provide important insight into the origin of H2O2 in vascular cells, and may partially account for the limited pharmacological effect of antioxidant treatments with O2*- scavengers that do not affect H2O2...
  5. pmc Cellular defenses against superoxide and hydrogen peroxide
    James A Imlay
    Department of Microbiology, University of Illinois, Urbana, IL 61801, USA
    Annu Rev Biochem 77:755-76. 2008
    ..Current research seeks to identify these, and bacteria comprise an exceptionally accessible experimental system that has provided many of the answers. This manuscript reviews recent developments and identifies remaining puzzles...
  6. ncbi Apocynin is not an inhibitor of vascular NADPH oxidases but an antioxidant
    Sabine Heumüller
    Institut für Kardiovaskuläre Physiologie, Johann Wolfgang Goethe Universitat, Theodor Stern Kai 7, D 60596 Frankfurt am Main, Germany
    Hypertension 51:211-7. 2008
    ..These observations indicate that apocynin predominantly acts as an antioxidant in endothelial cells and vascular smooth muscle cells and should not be used as an NADPH oxidase inhibitor in vascular systems...
  7. ncbi Superoxide activates mitochondrial uncoupling proteins
    Karim S Echtay
    Medical Research Council Dunn Human Nutrition Unit, Hills Road, Cambridge CB2 2XY, UK
    Nature 415:96-9. 2002
    ..Our findings indicate that the interaction of superoxide with UCPs may be a mechanism for decreasing the concentrations of reactive oxygen species inside mitochondria...
  8. pmc The sites and topology of mitochondrial superoxide production
    Martin D Brand
    Buck Institute for Age Research, 8001 Redwood Blvd, Novato, CA 94945, USA
    Exp Gerontol 45:466-72. 2010
    ....
  9. pmc Selective fluorescent imaging of superoxide in vivo using ethidium-based probes
    Kristine M Robinson
    Linus Pauling Institute, Department of Biochemistry and Biophysics, Oregon State University, Corvallis, OR 97331, USA
    Proc Natl Acad Sci U S A 103:15038-43. 2006
    ..Monitoring oxidation at both 396 and 510 nm of excitation wavelengths can facilitate the more selective detection of superoxide in vivo...
  10. ncbi Complex III releases superoxide to both sides of the inner mitochondrial membrane
    Florian L Muller
    Department of Cellular Biology, University of Texas Health Science Center, San Antonio, TX 78284 7762, USA
    J Biol Chem 279:49064-73. 2004
    ..This explains extramitochondrial release of superoxide but raises the question of how superoxide could reach the matrix. We discuss two models explaining this result...
  11. pmc Oxidation of tetrahydrobiopterin leads to uncoupling of endothelial cell nitric oxide synthase in hypertension
    Ulf Landmesser
    Division of Cardiology, Emory University School of Medicine and Atlanta Veterans Administration Hospital, 1639 Pierce Drive, Atlanta, GA 30322, USA
    J Clin Invest 111:1201-9. 2003
    ..Treatment strategies that increase tetrahydrobiopterin or prevent its oxidation may prove useful in preventing vascular complications of this common disease...
  12. ncbi Killing activity of neutrophils is mediated through activation of proteases by K+ flux
    Emer P Reeves
    Centre for Molecular Medicine, University College London, 5 University Street, London WC1E 6JJ, UK
    Nature 416:291-7. 2002
    ..We show that it is the proteases, thus activated, that are primarily responsible for the destruction of the bacteria...
  13. pmc Superoxide is a mediator of an altruistic aging program in Saccharomyces cerevisiae
    Paola Fabrizio
    Andrus Gerontology Center and Dept of Biological Sciences, University of Southern California, 3715 McClintock Avenue, Los Angeles, CA 90089 0191, USA
    J Cell Biol 166:1055-67. 2004
    ..The role of similar pathways in the regulation of longevity in organisms ranging from yeast to mice raises the possibility that mammals may also undergo programmed aging...
  14. ncbi Superoxide production and expression of nox family proteins in human atherosclerosis
    Dan Sorescu
    Department of Medicine, Emory University, Atlanta, GA 30322, USA
    Circulation 105:1429-35. 2002
    ....
  15. ncbi Mouse model of X-linked chronic granulomatous disease, an inherited defect in phagocyte superoxide production
    J D Pollock
    Department of Pediatrics, James Whitcomb Riley Hospital for Children, Indianapolis, Indiana, USA
    Nat Genet 9:202-9. 1995
    ..This animal model should aid in developing new treatments for CGD and in evaluating the role of phagocyte-derived oxidants in inflammation...
  16. ncbi Hyperglycemia increases mitochondrial superoxide in retina and retinal cells
    Yunpeng Du
    Department of Medicine, Case Western Reserve University, Cleveland, OH 44106 4951, USA
    Free Radic Biol Med 35:1491-9. 2003
    ....
  17. ncbi Mechanisms underlying endothelial dysfunction in diabetes mellitus
    U Hink
    Universitatskrankenhaus Eppendorf, Germany
    Circ Res 88:E14-22. 2001
    ..The full text of this article is available at http://www.circresaha.org...
  18. pmc NOX4 activity is determined by mRNA levels and reveals a unique pattern of ROS generation
    Lena Serrander
    Foundation for Medical Research, University of Geneva, 64 av de la Roseraie, 1205, Geneva, Switzerland
    Biochem J 406:105-14. 2007
    ..In conclusion, NOX4 has a distinct pharmacology and pattern of ROS generation. The close correlation between NOX4 mRNA and ROS generation might hint towards a function as an inducible NOX isoform...
  19. pmc Hydroethidine- and MitoSOX-derived red fluorescence is not a reliable indicator of intracellular superoxide formation: another inconvenient truth
    Jacek Zielonka
    Department of Biophysics and Free Radical Research Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA
    Free Radic Biol Med 48:983-1001. 2010
    ....
  20. pmc Superoxide flashes in single mitochondria
    Wang Wang
    Laboratories of Cardiovascular Sciences, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA
    Cell 134:279-90. 2008
    ..We propose that superoxide flashes could serve as a valuable biomarker for a wide variety of oxidative stress-related diseases...
  21. pmc Inhibition of GAPDH activity by poly(ADP-ribose) polymerase activates three major pathways of hyperglycemic damage in endothelial cells
    Xueliang Du
    Diabetes Research Center, Albert Einstein College of Medicine, Bronx, New York, USA
    J Clin Invest 112:1049-57. 2003
    ..Elevated glucose increased poly(ADP-ribosyl)ation of GAPDH in WT aortae, but not in the aortae from PARP-1-deficient mice. Thus, inhibition of PARP blocks hyperglycemia-induced activation of multiple pathways of vascular damage...
  22. ncbi Mechanism of superoxide and hydrogen peroxide formation by fumarate reductase, succinate dehydrogenase, and aspartate oxidase
    Kevin R Messner
    Department of Microbiology, University of Illinois, Urbana, Illinois 61801, USA
    J Biol Chem 277:42563-71. 2002
    ..In contrast, succinate dehydrogenase, with high potential clusters, generates O2*- exclusively. The identities of enzyme autoxidation products are significant because O2*- and H2O2 damage cells in different ways...
  23. pmc Myocardial ischemia results in tetrahydrobiopterin (BH4) oxidation with impaired endothelial function ameliorated by BH4
    Cristian Dumitrescu
    Davis Heart and Lung Research Institute, Division of Cardiovascular Medicine, Department of Internal Medicine, College of Medicine, Ohio State University, Columbus, OH 43210, USA
    Proc Natl Acad Sci U S A 104:15081-6. 2007
    ..Supplementation of BH(4) may therefore be an important therapeutic approach to reverse endothelial dysfunction in postischemic tissues...
  24. ncbi Novel competitive inhibitor of NAD(P)H oxidase assembly attenuates vascular O(2)(-) and systolic blood pressure in mice
    F E Rey
    Hypertension and Vascular Research Division, Henry Ford Hospital, Detroit, MI 48202-2689, USA
    Circ Res 89:408-14. 2001
    ..These data support the hypothesis that inhibition of the interaction of p47(phox) and gp91(phox) (or its homologues) can block O(2)(-) production and attenuate blood pressure elevation in mice...
  25. ncbi 2-(2-Fluorobenzamido)benzoate ethyl ester (EFB-1) inhibits superoxide production by human neutrophils and attenuates hemorrhagic shock-induced organ dysfunction in rats
    Huang Ping Yu
    Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan
    Free Radic Biol Med 50:1737-48. 2011
    ..Therefore, EFB-1 is a new inhibitor of cAMP-specific PDE that potently suppresses O(2•-) release and CD11b expression by human neutrophils and attenuates T/H-induced MOD in rats...
  26. ncbi Naloxone protects rat dopaminergic neurons against inflammatory damage through inhibition of microglia activation and superoxide generation
    B Liu
    Neuropharmacology Section, Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA
    J Pharmacol Exp Ther 293:607-17. 2000
    ....
  27. pmc Upregulation of Nox4 by hypertrophic stimuli promotes apoptosis and mitochondrial dysfunction in cardiac myocytes
    Tetsuro Ago
    Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, Newark, NJ 07103, USA
    Circ Res 106:1253-64. 2010
    ..NADPH oxidases are a major source of superoxide (O(2)(-)) in the cardiovascular system. The function of Nox4, a member of the Nox family of NADPH oxidases, in the heart is poorly understood...
  28. ncbi Mitochondrial alpha-ketoglutarate dehydrogenase complex generates reactive oxygen species
    Anatoly A Starkov
    Department of Neurology and Neuroscience, Weill Medical College, Cornell University, New York, New York 10021, USA
    J Neurosci 24:7779-88. 2004
    ..These mitochondria also produced significantly less H(2)O(2) than mitochondria isolated from their littermate wild-type mice. The data strongly indicate that KGDHC is a primary site of ROS production in normally functioning mitochondria...
  29. ncbi α-Linolenic acid intake attenuates myocardial ischemia/reperfusion injury through anti-inflammatory and anti-oxidative stress effects in diabetic but not normal rats
    Nianlin Xie
    Department of Cardiac Surgery, Xijing Hospital, Fourth Military Medical University, Xi an, China
    Arch Med Res 42:171-81. 2011
    ..The present study attempted to investigate the effects of ALA intake on MI/R injury in normal and diabetic rats and its mechanisms...
  30. ncbi Superoxide production in vascular smooth muscle contributes to oxidative stress and impaired relaxation in atherosclerosis
    F J Miller
    Department of Internal Medicine, University of Iowa College of Medicine and Cardiovascular Center, and Veterans Administration Medical Center, Iowa City, USA
    Circ Res 82:1298-305. 1998
    ..Reduction in endothelial O2-. levels is not sufficient to improve endothelium-dependent relaxation. Generation of reactive oxygen species within the media may contribute to vasomotor dysfunction in atherosclerosis...
  31. pmc Genome-wide transcriptional profiling of the Escherichia coli responses to superoxide stress and sodium salicylate
    P J Pomposiello
    Department of Cancer Cell Biology, Harvard School of Public Health, Boston, Massachusetts 02115, USA
    J Bacteriol 183:3890-902. 2001
    ..A large number of PQ- and NaSal-responsive genes have no known function, suggesting that many adaptive metabolic changes that ensue after stress remain uncharacterized...
  32. ncbi Nox4 as the major catalytic component of an endothelial NAD(P)H oxidase
    Tetsuro Ago
    Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Maidashi 3 1 1, Higashi ku, Fukuoka 812 8582, Japan
    Circulation 109:227-33. 2004
    ..However, the precise molecular structure and the mechanism of activation of the oxidase have remained poorly understood...
  33. pmc Against the oxidative damage theory of aging: superoxide dismutases protect against oxidative stress but have little or no effect on life span in Caenorhabditis elegans
    Ryan Doonan
    Institute of Healthy Ageing and Research Department of Genetics, Evolution and Environment, University College London, London WC1E 6BT, United Kingdom
    Genes Dev 22:3236-41. 2008
    ..However, loss of the extracellular Cu/ZnSOD sod-4 enhances daf-2 longevity and constitutive diapause, suggesting a signaling role for sod-4. Overall, these findings imply that O(2)(-) is not a major determinant of aging in C. elegans...
  34. ncbi Viscolin, a new chalcone from Viscum coloratum, inhibits human neutrophil superoxide anion and elastase release via a cAMP-dependent pathway
    Tsong Long Hwang
    Graduate Institute of Natural Products, College of Medicine, Chang Gung University, Kweishan 333, Taoyuan, Taiwan
    Free Radic Biol Med 41:1433-41. 2006
    ..In summary, viscolin is a novel inhibitor of PDE and might be useful for treatment of neutrophilic inflammation...
  35. pmc The mechanism of superoxide production by NADH:ubiquinone oxidoreductase (complex I) from bovine heart mitochondria
    Lothar Kussmaul
    Medical Research Council Dunn Human Nutrition Unit, Wellcome Trust Medical Research Council Building, Hills Road, Cambridge CB2 2XY, United Kingdom
    Proc Natl Acad Sci U S A 103:7607-12. 2006
    ..Therefore, our mechanism forms a foundation for formulating causative connections between complex I defects and pathological effects...
  36. ncbi The identification of primary sites of superoxide and hydrogen peroxide formation in the aerobic respiratory chain and sulfite reductase complex of Escherichia coli
    K R Messner
    Department of Microbiology, University of Illinois, Urbana, Illinois 61801, USA
    J Biol Chem 274:10119-28. 1999
    ..Thus these environmental parameters may also directly affect the O-2 and H2O2 loads that organisms must bear...
  37. pmc Cladielloides A and B: new eunicellin-type diterpenoids from an Indonesian octocoral Cladiella sp
    Yung Husan Chen
    National Museum of Marine Biology and Aquarium, Pingtung 944, Taiwan
    Mar Drugs 8:2936-45. 2010
    ..Cladielloide B (2) exhibited moderate cytotoxicity toward CCRF-CEM tumor cells and this compound displayed significant inhibitory effects on superoxide anion generation and elastase release by human neutrophils...
  38. pmc Detection and characterization of the product of hydroethidine and intracellular superoxide by HPLC and limitations of fluorescence
    Hongtao Zhao
    Department of Biophysics and Free Radical Research Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA
    Proc Natl Acad Sci U S A 102:5727-32. 2005
    ..We conclude that the HPLC/fluorescence assay using HE as a probe is more suitable [corrected] for detecting intracellular O(2)(.-)...
  39. pmc A Measurable increase in oxidative damage due to reduction in superoxide detoxification fails to shorten the life span of long-lived mitochondrial mutants of Caenorhabditis elegans
    Wen Yang
    Department of Biology, McGill University, Montreal, Quebec H3A 1B1, Canada
    Genetics 177:2063-74. 2007
    ..We discuss the significance of our findings in light of the oxidative stress theory of aging...
  40. pmc eNOS uncoupling and endothelial dysfunction in aged vessels
    Yang Ming Yang
    Department of Physiology, New York Medical College, Valhalla, NY 10595, USA
    Am J Physiol Heart Circ Physiol 297:H1829-36. 2009
    ....
  41. ncbi Superoxide reacts with hydroethidine but forms a fluorescent product that is distinctly different from ethidium: potential implications in intracellular fluorescence detection of superoxide
    Hongtao Zhao
    Biophysics Research Institute and Free Radical Research Center, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA
    Free Radic Biol Med 34:1359-68. 2003
    ..We conclude that the reaction between superoxide and HE forms a fluorescent marker product that is different from ethidium. Potential implications of this finding in intracellular detection and imaging of superoxide are discussed...
  42. ncbi Redox control of endothelial function and dysfunction: molecular mechanisms and therapeutic opportunities
    Shane R Thomas
    Centre for Vascular Research, School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia
    Antioxid Redox Signal 10:1713-65. 2008
    ....
  43. pmc Hv1 proton channels are required for high-level NADPH oxidase-dependent superoxide production during the phagocyte respiratory burst
    I Scott Ramsey
    Howard Hughes Medical Institute, Department of Neurobiology, Harvard Medical School, and Department of Cardiovascular Research, Manton Center for Orphan Disease, Children s Hospital, 320 Longwood Avenue, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 106:7642-7. 2009
    ..Despite significant reduction in superoxide production, Hv1(-/-) mice are able to clear several types of bacterial infections...
  44. ncbi Inhibitors of the quinone-binding site allow rapid superoxide production from mitochondrial NADH:ubiquinone oxidoreductase (complex I)
    Adrian J Lambert
    Medical Research Council Dunn Human Nutrition Unit, Hills Road, Cambridge CB2 2XY, United Kingdom
    J Biol Chem 279:39414-20. 2004
    ....
  45. pmc The ratio between tetrahydrobiopterin and oxidized tetrahydrobiopterin analogues controls superoxide release from endothelial nitric oxide synthase: an EPR spin trapping study
    Jeannette Vasquez-Vivar
    Biophysics Research Institute and Free Radical Research Center, Medical College of Wisconsin, Milwaukee, WI 53226, U S A
    Biochem J 362:733-9. 2002
    ..NO formation. Collectively, these results indicate that the ratio between oxidized and reduced BH(4) metabolites tightly regulates superoxide formation from eNOS. The pathological significance of this scenario is discussed...
  46. ncbi Assembly of the phagocyte NADPH oxidase
    William M Nauseef
    Inflammation Program and Department of Medicine, Roy J and Lucille A Carver College of Medicine, University of Iowa, D160 MTF, 2501 Crosspark Road, Coralville, IA 52241, USA
    Histochem Cell Biol 122:277-91. 2004
    ..This review summarizes data on the structural features of the phagocyte oxidase components and on the agonist-dependent conformational rearrangements that contribute to oxidase assembly and activation...
  47. ncbi Mitochondrial reactive oxygen species reduce insulin secretion by pancreatic beta-cells
    Koji Sakai
    Department of Metabolic Medicine, Kumamoto University School of Medicine, 1 1 1 Honjo, Japan
    Biochem Biophys Res Commun 300:216-22. 2003
    ..We propose that mitochondrial overwork is a potential mechanism causing impaired first-phase of GIIS in the early stages of diabetes mellitus...
  48. pmc Effects of p38 MAPK inhibition on early stages of diabetic retinopathy and sensory nerve function
    Yunpeng Du
    Case Western Reserve University, Cleveland, Ohio, USA
    Invest Ophthalmol Vis Sci 51:2158-64. 2010
    ....
  49. ncbi Topical administration of nepafenac inhibits diabetes-induced retinal microvascular disease and underlying abnormalities of retinal metabolism and physiology
    Timothy S Kern
    Medicine and Ophthalmology, 434 Biomedical Research Building, Case Western Reserve University, 10900 Euclid Ave, Cleveland, OH 44106, USA
    Diabetes 56:373-9. 2007
    ..Local inhibition of inflammatory pathways in the eye offers a novel therapeutic approach toward inhibiting the development of lesions of diabetic retinopathy...
  50. ncbi Molecular mechanisms of superoxide production by the mitochondrial respiratory chain
    Stefan Dröse
    Center for Membrane Proteomics, Johann Wolfgang Goethe Universitat, Frankfurt am Main, Germany
    Adv Exp Med Biol 748:145-69. 2012
    ..Regulatory contributions of other components of the respiratory chain, especially complex II (succinate:ubiquinone oxidoreductase) and the redox state of the ubiquinone pool (Q-pool) will be briefly discussed...
  51. ncbi High rates of superoxide production in skeletal-muscle mitochondria respiring on both complex I- and complex II-linked substrates
    Florian L Muller
    Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, Texas Research Park Campus, 15355 Lambda Drive, San Antonio, TX 78229 3900, USA
    Biochem J 409:491-9. 2008
    ....
  52. ncbi High glucose via peroxynitrite causes tyrosine nitration and inactivation of prostacyclin synthase that is associated with thromboxane/prostaglandin H(2) receptor-mediated apoptosis and adhesion molecule expression in cultured human aortic endothelial cel
    Ming Hui Zou
    Vascular Biology Unit, Whitaker Cardiovascular Institute, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts 02118, USA
    Diabetes 51:198-203. 2002
    ....
  53. ncbi Inhibition of NADPH oxidase activation in endothelial cells by ortho-methoxy-substituted catechols
    David K Johnson
    Department of Chemistry, State University of New York College at Geneseo, USA
    Endothelium 9:191-203. 2002
    ..These findings identify a metabolite of an ortho-methoxy-substituted catechol, which may be the active compound formed within stimulated ECs that prevents NADPH oxidase complex assembly and activation...
  54. ncbi Endothelial nitric oxide synthase dysfunction in diabetic mice: importance of tetrahydrobiopterin in eNOS dimerisation
    S Cai
    Department of Cardiovascular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DU, UK
    Diabetologia 48:1933-40. 2005
    ..In this regard, we investigated the role of tetrahydrobiopterin (BH4) bioavailability in regulating endothelial nitric oxide synthase (eNOS) activity, dimerisation and SO production in streptozotocin-induced diabetic mice...
  55. pmc Mitochondrial reactive oxygen species production in excitable cells: modulators of mitochondrial and cell function
    David F Stowe
    Anesthesiology Research Laboratories, Department of Anesthesiology, The Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA
    Antioxid Redox Signal 11:1373-414. 2009
    ....
  56. pmc VDAC-dependent permeabilization of the outer mitochondrial membrane by superoxide induces rapid and massive cytochrome c release
    M Madesh
    Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA
    J Cell Biol 155:1003-15. 2001
    ..Thus, O2*- triggers apoptosis via VDAC-dependent permeabilization of the mitochondrial outer membrane without apparent contribution of proapoptotic Bcl-2 family proteins...
  57. pmc Imaging superoxide flash and metabolism-coupled mitochondrial permeability transition in living animals
    Huaqiang Fang
    Institute of Molecular Medicine, College of Life Science, Peking University, Beijing 100871, China
    Cell Res 21:1295-304. 2011
    ....
  58. pmc Endothelial dihydrofolate reductase: critical for nitric oxide bioavailability and role in angiotensin II uncoupling of endothelial nitric oxide synthase
    Karel Chalupsky
    Section of Cardiology, Department of Medicine, Division of Biological Sciences and Pritzker School of Medicine, University of Chicago, Chicago, IL 60637, USA
    Proc Natl Acad Sci U S A 102:9056-61. 2005
    ..This signaling cascade may represent a universal mechanism underlying eNOS dysfunction under pathophysiological conditions associated with oxidant stress...
  59. ncbi NOX5 is expressed at the plasma membrane and generates superoxide in response to protein kinase C activation
    Lena Serrander
    Foundation for Medical Research, University of Geneva, 64 av de la Roseraie, 1205 Geneva, Switzerland
    Biochimie 89:1159-67. 2007
    ..In summary, we demonstrate that NOX5 can be found intracellularly and at the cell surface. We also describe that it can be activated through protein kinase C, in addition to its Ca(2+) activation...
  60. ncbi Mechanisms of increased vascular superoxide production in human diabetes mellitus: role of NAD(P)H oxidase and endothelial nitric oxide synthase
    Tomasz J Guzik
    Department of Cardiovascular Medicine, University of Oxford, Oxford, UK
    Circulation 105:1656-62. 2002
    ..We characterized the sources and mechanisms underlying vascular superoxide production in human blood vessels from diabetic patients with coronary artery disease compared with nondiabetic patients...
  61. pmc Superoxide production by NADH:ubiquinone oxidoreductase (complex I) depends on the pH gradient across the mitochondrial inner membrane
    Adrian J Lambert
    Medical Research Council Dunn Human Nutrition Unit, Hills Road, Cambridge CB2 2XY, UK
    Biochem J 382:511-7. 2004
    ....
  62. ncbi Direct evidence of a role for Nox2 in superoxide production, reduced nitric oxide bioavailability, and early atherosclerotic plaque formation in ApoE-/- mice
    Courtney P Judkins
    Department of Pharmacology, Monash University, Clayton, Victoria, Australia
    Am J Physiol Heart Circ Physiol 298:H24-32. 2010
    ....
  63. pmc Tetrahydrobiopterin-dependent preservation of nitric oxide-mediated endothelial function in diabetes by targeted transgenic GTP-cyclohydrolase I overexpression
    Nicholas J Alp
    Department of Cardiovascular Medicine, University of Oxford, John Radcliffr Hospital, United Kingdom
    J Clin Invest 112:725-35. 2003
    ..These findings indicate that BH4 is an important mediator of eNOS regulation in diabetes and is a rational therapeutic target to restore NO-mediated endothelial function in diabetes and other vascular disease states...
  64. ncbi Transcriptional upregulation of mitochondrial uncoupling protein 2 protects against oxidative stress-associated neurogenic hypertension
    Samuel H H Chan
    Center for Translational Research in Biomedical Sciences, Chang Gung Memorial Hospital Kaohsiung Medical Center, Republic of China
    Circ Res 105:886-96. 2009
    ..Mitochondrial uncoupling proteins (UCPs) belong to a superfamily of mitochondrial anion transporters that uncouple ATP synthesis from oxidative phosphorylation and mitigates mitochondrial reactive oxygen species production...
  65. ncbi Quantitative regulation of intracellular endothelial nitric-oxide synthase (eNOS) coupling by both tetrahydrobiopterin-eNOS stoichiometry and biopterin redox status: insights from cells with tet-regulated GTP cyclohydrolase I expression
    Mark J Crabtree
    Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom
    J Biol Chem 284:1136-44. 2009
    ....
  66. ncbi Rosmarinic acid inhibits the formation of reactive oxygen and nitrogen species in RAW264.7 macrophages
    Shanlou Qiao
    Department of Biochemistry, Aichi Medical University School of Medicine, Nagakute, Aichi 480 1195, Japan
    Free Radic Res 39:995-1003. 2005
    ....
  67. pmc New Briarane diterpenoids from the gorgonian coral Junceella juncea
    Jiun Yang Chang
    School of Pharmacy, College of Medicine, National Taiwan University, Jen Ai Rd Sec 1, Taipei 101 200, Taiwan
    Mar Drugs 10:1321-30. 2012
    ..The anti-inflammatory activities tested on superoxide anion generation and elastase release by human neutrophils in response to FMLP/CB were evaluated...
  68. pmc Nicotinamide adenine dinucleotide phosphate reduced oxidase 5 (Nox5) regulation by angiotensin II and endothelin-1 is mediated via calcium/calmodulin-dependent, rac-1-independent pathways in human endothelial cells
    Augusto C Montezano
    Kidney Research Centre, University of Ottawa, 451 Smyth Rd, Ottawa, K1H 8M5, Ontario, Canada
    Circ Res 106:1363-73. 2010
    ..Although Nox5 (Nox2 homolog) has been identified in the vasculature, its regulation and functional significance remain unclear...
  69. pmc Activation of neuronal NMDA receptors induces superoxide-mediated oxidative stress in neighboring neurons and astrocytes
    Reno C Reyes
    Department of Neurology, University of California San Francisco, USA
    J Neurosci 32:12973-8. 2012
    ..These findings show that activation of NMDA receptors on one neuron can lead to oxidative stress and cell death in neighboring neurons and astrocytes by a process involving the extracellular release of superoxide by NOX2...
  70. ncbi Sildenafil inhibits the formation of superoxide and the expression of gp47 NAD[P]H oxidase induced by the thromboxane A2 mimetic, U46619, in corpus cavernosal smooth muscle cells
    Anthony J Koupparis
    Urology and Bristol Heart Institute, Bristol Royal Infirmary, Bristol, UK
    BJU Int 96:423-7. 2005
    ..To assess the effect of sildenafil on superoxide formation and p47(phox) (the active subunit of NADPH oxidase) expression in cultured corpus cavernosal smooth muscle cells (CVSMCs)...
  71. pmc Oxygen glucose deprivation in rat hippocampal slice cultures results in alterations in carnitine homeostasis and mitochondrial dysfunction
    Thomas F Rau
    Department of Biomedical and Pharmaceutical Sciences, University of Montana, Missoula, Montana, United States of America
    PLoS ONE 7:e40881. 2012
    ..Thus, we conclude that LCAR supplementation preserves the key enzymes responsible for maintaining carnitine homeostasis and preserves both cell viability and synaptic transmission after OGD...
  72. ncbi 20-hydroxyeicosatetraenoic acid causes endothelial dysfunction via eNOS uncoupling
    Jennifer Cheng
    Department of Pharmacology, New York Medical College, Valhalla, NY 10595, USA
    Am J Physiol Heart Circ Physiol 294:H1018-26. 2008
    ....
  73. pmc Membrane raft-lysosome redox signalling platforms in coronary endothelial dysfunction induced by adipokine visfatin
    Min Xia
    Department of Pharmacology and Toxicology, Medical College of Virginia Campus, Virginia Commonwealth University, 410 N 12th Street, Richmond, VA 23298, USA
    Cardiovasc Res 89:401-9. 2011
    ..The present study was designed to test a hypothesis that visfatin causes coronary endothelial dysfunction through lysosome trafficking and fusion to cell membranes, membrane raft (MR) clustering, and formation of redox signalosomes...
  74. ncbi Small heat shock proteins, IbpA and IbpB, are involved in resistances to heat and superoxide stresses in Escherichia coli
    M Kitagawa
    Department of Biotechnology and High Technology Research Center, Kansai University, Yamate cho 3 3 35, Suita, Osaka, Japan
    FEMS Microbiol Lett 184:165-71. 2000
    ..The heat sensitivity of a rpoH amber mutant was partially suppressed by the overexpression of plac::ibpAB. These results suggest that IbpA and IbpB may be involved in the resistances to heat and oxidative stress...
  75. ncbi Mitochondrial superoxide: production, biological effects, and activation of uncoupling proteins
    Martin D Brand
    MRC Dunn Human Nutrition Unit, Cambridge CB2 2XY, UK
    Free Radic Biol Med 37:755-67. 2004
    ..More recently evolved roles of uncoupling proteins are in adaptive thermogenesis (UCP1) and perhaps as part of a signaling pathway to regulate insulin secretion in pancreatic beta cells (UCP2)...
  76. pmc Protective effect of extracellular superoxide dismutase on endothelial function during aging
    Donald D Lund
    Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52242 1081, USA
    Am J Physiol Heart Circ Physiol 296:H1920-5. 2009
    ..In conclusion, endogenous ecSOD plays an important role in protection against endothelial dysfunction during aging...
  77. ncbi Effect of gender on NADPH-oxidase activity, expression, and function in the cerebral circulation: role of estrogen
    Alyson A Miller
    Department of Pharmacology, Monash University, Clayton, Victoria, Australia
    Stroke 38:2142-9. 2007
    ..This study tested whether NADPH-oxidase activity, expression, and functional effects on vascular tone are influenced by gender in the rat cerebral circulation and whether such differences are estrogen-dependent...
  78. ncbi The circularly permuted yellow fluorescent protein cpYFP that has been used as a superoxide probe is highly responsive to pH but not superoxide in mitochondria: implications for the existence of superoxide 'flashes'
    Markus Schwarzlander
    Department of Plant Science, University of Oxford, South Parks Road, Oxford OX1 3RB, UK
    Biochem J 437:381-7. 2011
    ..In contrast, genetic and pharmacological manipulation of matrix superoxide had no detectable effect on the cpYFP signal. These findings question the existence of superoxide flashes in mitochondria...
  79. ncbi Reactive oxygen species as mediators of angiotensin II signaling
    K K Griendling
    Division of Cardiology, School of Medicine, Emory University, 319 WMB, 1639 Pierce Drive, 30322, Atlanta, GA 30322, USA
    Regul Pept 91:21-7. 2000
    ..Future work will be directed towards identifying other important redox-sensitive signaling pathways and their relationship to the physiology and pathophysiology of the renin-angiotensin system...
  80. ncbi Stoichiometric relationships between endothelial tetrahydrobiopterin, endothelial NO synthase (eNOS) activity, and eNOS coupling in vivo: insights from transgenic mice with endothelial-targeted GTP cyclohydrolase 1 and eNOS overexpression
    Jennifer K Bendall
    Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, United Kingdom
    Circ Res 97:864-71. 2005
    ..These data indicate that eNOS coupling is directly related to eNOS-BH4 stoichiometry even in the absence of a vascular disease state. Endothelial BH4 availability is a pivotal regulator of eNOS activity and enzymatic coupling in vivo...
  81. ncbi Endothelial cell superoxide generation: regulation and relevance for cardiovascular pathophysiology
    Jian Mei Li
    Department of Cardiology, GKT School of Medicine, King s College of London, SE5 9PJ, UK
    Am J Physiol Regul Integr Comp Physiol 287:R1014-30. 2004
    ....
  82. pmc Endothelial NO and O₂·⁻ production rates differentially regulate oxidative, nitroxidative, and nitrosative stress in the microcirculation
    Saptarshi Kar
    Department of Biomedical Engineering, Wayne State University, Detroit, MI 48202, USA
    Free Radic Biol Med 63:161-74. 2013
    ....
  83. pmc Contribution of guanine nucleotide exchange factor Vav2 to hyperhomocysteinemic glomerulosclerosis in rats
    Fan Yi
    Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, 410 N 12th St, Richmond, VA 23298, USA
    Hypertension 53:90-6. 2009
    ..We concluded that Vav2-mediated activation of NADPH oxidase is an important initiating mechanism resulting in hyperhomocysteinemic glomerular injury through enhanced local oxidative stress...
  84. pmc Trimetazidine, administered at the onset of reperfusion, ameliorates myocardial dysfunction and injury by activation of p38 mitogen-activated protein kinase and Akt signaling
    Mahmood Khan
    Division of Cardiovascular Medicine, Department of Internal Medicine, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio 43210, USA
    J Pharmacol Exp Ther 333:421-9. 2010
    ..The study emphasizes the importance of administering TMZ before reflow to prevent reperfusion-mediated cardiac injury and dysfunction...
  85. pmc Mitochondrial superoxide radicals mediate programmed cell death in Trypanosoma cruzi: cytoprotective action of mitochondrial iron superoxide dismutase overexpression
    Lucia Piacenza
    Departamento de Bioquimica, Center for Free Radical and Biomedical Research, Facultad de Medicina, Universidad de la Republica, Montevideo, Uruguay
    Biochem J 403:323-34. 2007
    ....
  86. ncbi Superoxide sensitivity of the Escherichia coli aconitase
    P R Gardner
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710
    J Biol Chem 266:19328-33. 1991
    ....
  87. ncbi Differential roles of PKCalpha and PKCepsilon in controlling the gene expression of Nox4 in human endothelial cells
    Hui Xu
    Department of Pharmacology, Johannes Gutenberg University, D 55131 Mainz, Germany
    Free Radic Biol Med 44:1656-67. 2008
    ..Both effects could be reduced by inhibition of NADPH oxidase. Thus, a selective inhibition/knockdown of PKCalpha may represent a novel therapeutic strategy for vascular disease...
  88. ncbi Transcriptional upregulation of brain-derived neurotrophic factor in rostral ventrolateral medulla by angiotensin II: significance in superoxide homeostasis and neural regulation of arterial pressure
    Samuel H H Chan
    Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Taiwan 813, Republic of China
    Circ Res 107:1127-39. 2010
    ..Emerging evidence suggests that brain-derived neurotrophic factor (BDNF) manifests "nontrophic" actions...
  89. ncbi Contractile activity-induced oxidative stress: cellular origin and adaptive responses
    A McArdle
    Department of Medicine, University of Liverpool, Liverpool L69 3GA, United Kingdom
    Am J Physiol Cell Physiol 280:C621-7. 2001
    ..These changes occurred in the absence of overt damage to the muscle cells...
  90. ncbi Contribution of nitric oxide, superoxide anion, and peroxynitrite to activation of mitochondrial apoptotic signaling in hippocampal CA3 subfield following experimental temporal lobe status epilepticus
    Yao Chung Chuang
    Department of Neurology, Chang Gung Memorial Hospital Kaohsiung Medical Center, Chang Gung University College of Medicine, Taiwan, Republic of China
    Epilepsia 50:731-46. 2009
    ....
  91. ncbi IFN-beta impairs superoxide-dependent parasite killing in human macrophages: evidence for a deleterious role of SOD1 in cutaneous leishmaniasis
    Ricardo Khouri
    Laboratory of Immunoregulation and Microbiology, Centro de Pesquisa Gonçalo Moniz, Fundacao Oswaldo Cruz, Salvador Bahia, Brazi
    J Immunol 182:2525-31. 2009
    ..amazonensis as well as L. braziliensis infection, major human pathogens...
  92. ncbi Superoxide activates mitochondrial uncoupling protein 2 from the matrix side. Studies using targeted antioxidants
    Karim S Echtay
    Medical Research Council Dunn Human Nutrition Unit, Hills Road, Cambridge CB2 2XY, UK
    J Biol Chem 277:47129-35. 2002
    ..We conclude that superoxide (or its products) exerts its uncoupling effect by activating the proton transport mechanism of uncoupling proteins at the matrix side of the mitochondrial inner membrane...
  93. pmc Evidence for two sites of superoxide production by mitochondrial NADH-ubiquinone oxidoreductase (complex I)
    Jason R Treberg
    Buck Institute for Research on Aging, Novato, California 94945, USA
    J Biol Chem 286:27103-10. 2011
    ....
  94. ncbi Signaling functions of free radicals superoxide & nitric oxide under physiological & pathological conditions
    Igor B Afanas'ev
    Vitamin Research Institute, Moscow, Russia
    Mol Biotechnol 37:2-4. 2007
    ..In conclusion, interplay between superoxide and nitric oxide, one of major factors of aging development, is considered...
  95. ncbi Suppressing production of reactive oxygen species (ROS) for influenza A virus therapy
    Ross Vlahos
    Respiratory Research Group, Department of Pharmacology, The University of Melbourne, Victoria, Australia
    Trends Pharmacol Sci 33:3-8. 2012
    ..Therefore, we propose that Nox2 oxidase inhibitors, in combination with current therapeutics (i.e. antivirals and vaccines), could be useful for suppression of influenza A virus-induced lung disease...
  96. ncbi Wogonin sensitizes resistant malignant cells to TNFalpha- and TRAIL-induced apoptosis
    Stefanie C Fas
    Tumor Immunology Program D030, German Cancer Research Center DKFZ, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
    Blood 108:3700-6. 2006
    ..Our data suggest a potential use of wogonin as a TNFalpha or TRAIL adjuvant for cancer treatment. Our data also demonstrate how a herbal compound enhances killing of tumor cells with reduced side effects compared with other treatments...
  97. pmc Treatment of CoQ(10) deficient fibroblasts with ubiquinone, CoQ analogs, and vitamin C: time- and compound-dependent effects
    Luis C Lopez
    Department of Neurology, Columbia University Medical Center, New York, New York, United States of America
    PLoS ONE 5:e11897. 2010
    ..However, published studies suggest that different ubiquinone analogs may produce divergent effects on oxidative phosphorylation and oxidative stress...
  98. pmc Gp91phox (NOX2) in classically activated microglia exacerbates traumatic brain injury
    Kenji Dohi
    Department of Emergency and Critical Care Medicine, Showa University School of Medicine, Shinagawa ku, Tokyo 142 8555, Japan
    J Neuroinflammation 7:41. 2010
    ..We also used a microglial cell line to determine the activated cell phenotype that contributes to gp91phox generation...
  99. 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...
  100. pmc Tryptophan/kynurenine metabolism in human leukocytes is independent of superoxide and is fully maintained in chronic granulomatous disease
    Suk See De Ravin
    Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Blood 116:1755-60. 2010
    ....
  101. ncbi Endothelial Nox2 overexpression potentiates vascular oxidative stress and hemodynamic response to angiotensin II: studies in endothelial-targeted Nox2 transgenic mice
    Jennifer K Bendall
    Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, OX39DU, UK
    Circ Res 100:1016-25. 2007
    ..Endothelial cell Nox2-containing NADPH oxidase plays an important functional role in vascular redox signaling...

Research Grants71

  1. Anti-tumor properties of curcumin in oral cancers: role of thioredoxin reductase
    STEPHEN WILLIAM TUTTLE; Fiscal Year: 2010
    ..However, curcumin has been effective in tumors, such as colon and HNC, where direct access to the drug is possible. The primary aim of this study is to develop curcumin as a chemotherapeutic and radiation sensitizer for treating HNC.. ..
  2. Correction of glutathione deficiency for treatment of diabetic nephropathy
    Paolo Fanti; Fiscal Year: 2013
    ....
  3. A Hybrid PARP Inhibitor and Redox Catalyst for Lung Transplantation
    GARRY JOHN SOUTHAN; Fiscal Year: 2012
    ..At present there are no approved prophylactic measures. We are developing a novel drug that targets the basic mechanisms of this condition and will test this agent in a clinically-relevant animal model. ..
  4. Peroxynitrite Decomposition Catalyst and Nitric Oxide Donor for Endotoxemia
    GARRY JOHN SOUTHAN; Fiscal Year: 2012
    ..We will now test this agent in a series of investigations in order to determine the optimal dose, to confirm the mechanism of action, and to establish the window of opportunity after disease onset within which therapy may be initiated. ..
  5. Roles of Nitric Oxide and Superoxide in Cystitis
    ANTHONY JOHN KANAI; Fiscal Year: 2013
    ..Hypothesis: FA-NO2 are radioprotective by desensitizing TRPA1 and TRPV1 channels and BDNF-AB and NGF-AB are therapeutic by inhibiting nerve growth and sensitization in bladder and spinal cord. ..
  6. Epigenetic mechanisms relevant to the pathogenesis of ALS
    Neil W Kowall; Fiscal Year: 2013
    ..The urgent need for such studies is highlighted by the prospect that hundreds of thousands of future veterans may be at increased risk for this devastating disease. ..
  7. Enterococcus faecalis, Colorectal Cancer, and Bystander Effects
    Mark M Huycke; Fiscal Year: 2012
    ..These results will identify new approaches and targets for preventing sporadic colorectal cancer. ..
  8. Mitochondrial Dysfunction and Adipose Insulin Resistance
    David A Bernlohr; Fiscal Year: 2013
    ..If the hypothesis is proven to be correct, the study would be immediately translatable to human biology and afford a new view of how type 2 diabetes may be combated. ..
  9. DNA methylation of extracellular superoxide dismutase in pulmonary hypertension
    EVA NOZIK GRAYCK; Fiscal Year: 2012
    ..abstract_text> ..
  10. A Hybrid Katp Channel Opener to Prevent Radiocontrast-Induced Nephropathy
    Kanneganti Murthy; Fiscal Year: 2012
    ..We now propose to test this agent in a clinically-relevant small animal model of radiocontrast-induced kidney failure. ..
  11. Nanoparticle Coupled Antioxidants for Respiratory Illness in Veterans
    RODNEY JON SCHLOSSER; Fiscal Year: 2013
    ..We will use a murine model of allergic fungal rhinosinusitis with exacerbation by smoke or DEP exposure to determine the efficacy of antiMUC1-SOD/CAT-NPs. ..
  12. Vascular dysfunction and oxidative stress in primary amyloidosis
    RAYMOND QUEZON MIGRINO; Fiscal Year: 2010
    ..The research will provide important information on the basis and possible treatment of primary systemic amyloidosis that may lead to improvement in survival in these patients. ..
  13. Systemic Inflammation and Central Nervous System Dysfunction
    Laura L Dugan; Fiscal Year: 2013
    ..abstract_text> ..
  14. Prevention of UV-induced carcinogenesis by cyanidin-3-glucoside
    Xianglin Shi; Fiscal Year: 2013
    ..Present study attempts to identify cyanidin-3-glucoside, a plant-derived compound, as a mechanism-based preventive agent against UV-induced skin cancers. ..
  15. Protein Nitration in the Placenta
    Leslie Myatt; Fiscal Year: 2012
    ....
  16. REGULATION OF PULMONARY CIRCULATION IN FETUS AND NEWBORN
    Girija G Konduri; Fiscal Year: 2013
    ..These studies will identify an important new source of oxidative stress in PPHN. These observation may lead to new targeted therapies to improve vasodilation and oxygenation in PPHN. ..
  17. Hybrid Katp Channel Opener and Redox Catalyst for Lung Transplantation
    Prakash Jagtap; Fiscal Year: 2013
    ..R-801 therapy is expected to translate into decreased primary graft dysfunction and mortality after lung transplant. ..
  18. Conference on Autonomic Regulation of Cardiovascular Function in Health and Disea
    Martin Frank; Fiscal Year: 2012
    ..At least 1 symposium and several talks will be dedicated to sympathetic regulation in humans. These talks will include heart failure, hypertension, POTS, panic disorder and obesity/metabolic syndrome. ..
  19. Small Molecule targeting of NADPH oxidase in neutrophils
    Marie Dominique Filippi; Fiscal Year: 2010
    ..Therefore, our study will help delivering a novel pharmaceutical target, and suitable lead compounds for the treatment of lung inflammation, such as ALI and ARDS. ..
  20. Role of Peroxidasin in Glomerular Matrix Homeostasis
    Gautam Bhave; Fiscal Year: 2013
    ..Ultimately, Dr. Bhave hopes to translate his seminal biochemical discovery into an independent line of investigation examining the role of peroxidasin in matrix remodeling and expansion in renal disease. ..
  21. Genetic Studies of Optic Atrophy
    Taosheng Huang; Fiscal Year: 2012
    ..This study will allow us to understand how mutations of OPA1 cause optic atrophy and explore its novel function in lifespan and provide us a potential opportunity to develop treatments for the disease. ..
  22. X chromosome, injury and infection
    Zoltan Spolarics; Fiscal Year: 2012
    ..Better understanding of the protecting cellular mechanisms that are in effect during septic conditions could lead to advanced protocols in treating the critically ill. ..
  23. Prevention of Inherited Retinal Diseases by Therapeutic Rare Earth Nanoparticles
    JAMES FRANCIS MCGINNIS; Fiscal Year: 2010
    ..The nanoceria are expected to function in humans as they do in other mammals and therefore should preserve vision and prevent blindness in humans. ..
  24. Complex I: Role of L Subunit in Proton Translocation
    Steven B Vik; Fiscal Year: 2011
    ..The work in described in this proposal will allow greater understanding of key aspects of the functioning of Complex I. ..
  25. A Novel Thioredoxin Mimetic Prodrug for Prevention of Bronchopulmonary Dysplasia
    Prakash Jagtap; Fiscal Year: 2013
    ..The heart will undergo morphometric analysis for evidence of PAH (as shown by right ventricular (RV) hypertrophy). ..
  26. Mitochondrial Dysfunction and Adipose Insulin Resistance
    DAVID BERNLOHR; Fiscal Year: 2009
    ..Aim 3. Develop and characterize aP2-HA-GSTA4 transgenic mice maintained on low and high fat diets. Aim 4. Characterize the regulation of insulin signaling by the Trx2-ASK1-JNK pathway in animal and cell culture models...
  27. N-Acetylcysteine and Milk Thistle for Treatment of Diabetic Nephropathy
    Paolo Fanti; Fiscal Year: 2011
    ..Throughout the trial, we will monitor the safety and tolerability of this combination treatment. ..
  28. PET Imaging of Myocardial Oxidative Stress in T2DM
    KOORESH ISAAC SHOGHI; Fiscal Year: 2013
    ..abstract_text> ..
  29. Roles of oxidation and inflammation in aortic stiffening
    David G Harrison; Fiscal Year: 2013
    ..Our combined expertise in the physiology of hypertension, connective tissue biochemistry and cardiovascular histomorphology place us in a unique position to pursue these directions of research. ..
  30. Metabolic regulation of diabetic nephropathy
    Karen Block; Fiscal Year: 2013
    ..This work may have major therapeutic implications. ..
  31. Pharmacologic Interventions for Cardiovascular Disease in Obstructive Sleep Apnea
    Barbara J Morgan; Fiscal Year: 2013
    ..These interventions are novel, relevant, unobtrusive, relatively inexpensive, and could drasticallv change the treatment and possible prevention of cardiovascular disease in OSA. ..
  32. PARP inhibitor and Redox Catalyst Conjugate for Traumatic Brain Injury
    Kanneganti Murthy; Fiscal Year: 2012
    ..We are developing a novel drug that targets the basic mechanisms of this condition and will test this agent in a clinically-relevant animal model. ..
  33. Ca Signaling in Progression of Amyotrophic Lateral Sclerosis in Skeletal Muscle
    Jingsong Zhou; Fiscal Year: 2013
    ....
  34. Citrulline to Prevent or Mitigate Acute Lung Injury in Severe Sepsis
    Todd W Rice; Fiscal Year: 2013
    ..P/F and S/F ratios and lung injury score will be compared to evaluate the extent of ALI. Differences in clinical outcomes, including organ dysfunction, ventilator time, and survival will also be evaluated. ..
  35. Role of Potent Trophic Factors on Glia and Motor Neurons in ALS
    Brian K Kaspar; Fiscal Year: 2013
    ..We will subsequently test the optimal combination of these factors using gene delivery in a rodent model of this devastating disease in order to define an optimal therapy for this debilitating disorder. ..
  36. Contribution of c-Jun N-terminal kinase activity to vestibular schwannoma growth
    Marlan R Hansen; Fiscal Year: 2013
    ..Inhibition of JNK activity increases accumulation of reactive oxygen species (ROS), including mitochondrial superoxides. Further ROS scavengers prevent apoptosis in VS cells with suppressed JNK, implying that the prosurvival ..
  37. Brain Delivery of Nanoformulated Superoxide Dismutase
    Erin G Rosenbaugh; Fiscal Year: 2013
    ..In addition to the proposed scientific research, this fellowship will support the applicant's participation in nanotechnology-based coursework and career development. ..
  38. Colitis Induced by immune responses to luminal bacteria-mouse
    Ryan B Sartor; Fiscal Year: 2012
    ....
  39. INTERACTION OF THE ESTROGEN RECEPTOR WITH DNA
    ANN NARDULLI; Fiscal Year: 2013
    ..Our studies will provide critical new information about the role of a variety of estrogens and progestins in the brain and aid in the design of more effective hormonal treatments for women of all ages. ..
  40. Scavenging of Reactive Oxygen and Nitrogen Species by Cobalamins
    NICOLA ELIZABETH BRASCH; Fiscal Year: 2011
    ..Given a rapidly aging population, the study of the therapeutic potential of vitamin B12 is highly relevant since B12 deficiency is increasingly common, especially amongst the elderly. ..
  41. Mechanism of Irradiation Pulmonary Fibrosis
    Joel S Greenberger; Fiscal Year: 2012
    ..Project Narrative This irradiation application addresses a critical problem in managing the side effects of thoracic radiotherapy for lung and esophagus cancer. ..
  42. Redox regulation of phagocyte NOX2 in inflammation and aging
    Robert A Clark; Fiscal Year: 2013
    ....
  43. The Effects of PP2A on TNF Signaling and Smoke-Induced Lung Injury
    Robert F Foronjy; Fiscal Year: 2013
    ..Importantly, our findings will have important implications for other diseases where TNF signaling and inflammation play a central role. ..
  44. Novel pathways for fat burning that protects from high fat diet-induced metabolic
    Sihem Boudina; Fiscal Year: 2013
    ..abstract_text> ..
  45. Enhance Production of Functional Recombinant Human Protein C Variant In Mammalian
    Nienwen Chow; Fiscal Year: 2010
    ..This application seeks to develop a potential new therapeutic designed to protect blood vessels as well as neurons in the ALS-affected regions. ..
  46. Molecular Mechanism of Acrolein-Induced Vascular Toxicity: Role of PPAR gamma and
    Zivar Yousefipour; Fiscal Year: 2013
    ....
  47. Evaluating Novel Multi-kinase Peptide Inhibitors as a Treatment for Rheumatoid Ar
    DAVID MEN HWEI TSAI; Fiscal Year: 2013
    ..The long term goal of this project is to develop a safe, effective, and cost-efficient therapy to treat RA. ..
  48. NOX1 and NOX2 as Therapeutic Targets in Influenza
    JOHN DAVID LAMBETH; Fiscal Year: 2013
    ....
  49. Glutathione in mitochondrial dysfunction and disease progression in ALS-models
    Marcelo R Vargas; Fiscal Year: 2011
    ..One will also investigate possible ways to restore normal mitochondrial function as a therapy for ALS. ..
  50. Nitric Oxide in Pulmonary Hypertension
    Serpil C Erzurum; Fiscal Year: 2013
    ..Overall our goals are to define the pathophysiology of the abnormal vascular growth in PAH, and in so doing, apply the knowledge to improve the care of patients. ..
  51. Regulation of Cardiac Kv Channel Expression
    Edwin S Levitan; Fiscal Year: 2013
    ..Elucidating this pathway and its downstream effects on channels and other cardiac targets may lead to new therapies for treating heart failure. ..
  52. Mitochondrial Mechanisms of Programmed Necrosis in the Aged Female Heart
    Alexandra M Machikas; Fiscal Year: 2013
    ..The findings from this study will be invaluable in establishing the phenotype of cell death characteristic of I/R injury in the aged female heart and may supply clear evidence of the mitochondria as a therapeutic target for AMI. ..
  53. Transplantation of Reduced-Size Fatty Livers
    Zhi Zhong; Fiscal Year: 2010
    ....
  54. A Novel Murine Model of Chronic Inflammatory Periodontitus
    Helieh S Oz; Fiscal Year: 2010
    ..Specific aims for this proposal will examine targeted antioxidant therapies using mouse models of oral disease as a potential strategy for adjunctive management of human periodontitis. ..
  55. Deacetylation of mitochondrial proteins protect neurons from ischemic injury
    Conrad Alano; Fiscal Year: 2013
    ....
  56. Inhibitors of S. aureus bNOS for adjunctive therapy
    Donald T Moir; Fiscal Year: 2013
    ..These new drugs will prolong the duration of effective concentrations of existing antibiotics, thus reducing selection for resistance and improving therapy. ..
  57. Arsenic co-carcinogenesis with UVR: nitrosation and oxidation of target proteins
    Ke Jian Liu; Fiscal Year: 2013
    ..Additionally, these studies may lead to testable hypotheses regarding potential arsenic targets in cancer and other arsenic-associated diseases. ..
  58. Reperfusion and Neurovascular Injury in Stroke
    Pak H Chan; Fiscal Year: 2013
    ....
  59. Mechanisms and metabolic implications of LRP130 in NAFLD
    Marcus P Cooper; Fiscal Year: 2013
    ..This proposal will investigate the role of a gene called LRP130 in fatty liver disease, and may provide new ways to treat diabetes and heart disease. ..
  60. Therapeutic Strategies for Neonatal Hypoxic-Ischemic Encephalopathy
    RAYMOND CHARLES KOEHLER; Fiscal Year: 2012
    ....
  61. Inflammation and Repair in Cardiac Ischemia-Reperfusion
    Lewis C Becker; Fiscal Year: 2011
    ..abstract_text> ..
  62. Mechanisms of endothelial barrier phenotypes in sickle cell disease
    SOLOMON FIIFI OFORI-ACQUAH; Fiscal Year: 2013
    ..response in transgenic mice [2] Determine whether Nrf2 is essential for protection of the endothelium in sickle cell disease [3] Determine whether lung endothelial barrier integrity in sickle cell disease is dependent on NQO1 activity ..
  63. ADENOSINE AND ANTIOXIDANT ENZYMES
    Vickram Ramkumar; Fiscal Year: 1999
    ..Taken together, these studies will explore a novel mechanism of cytoprotection provided by adenosine and might contribute to the development of new treatments for myocardial and cerebral ischemia. ..
  64. Selenium Coated Dialysis Catheters for Reduced Biofilm Formation
    Eric Tobin; Fiscal Year: 2009
    ..High local concentrations of these superoxides cause lysis of bacterial cells, and could be particularly effective in preventing biofilm formation, since the ..
  65. Mitochondrial SOD & Breast Cancer Risk-Mechanism
    JAMES YAGER; Fiscal Year: 2003
    ..The advantage of this approach is that it will provide two sublines of identical genetic backgrounds and biochemistry except for the differences in the MnSOD import sequences ..
  66. GENETIC RESPONSE TO OXIDATIVE STREET IN E COLI
    SPENCER FARR; Fiscal Year: 1993
    ..V) to determine the relationship between the macromolecular synthesis operon and recovery of macromolecular synthesis after oxidative stress...
  67. MODELS FOR EXPLORING FREE RADICAL DAMAGE
    Julie Andersen; Fiscal Year: 1999
    ....
  68. Renal Control of Blood Pressure in Early Diabetes
    Michael Brands; Fiscal Year: 2007
    ..whether increased SOD1 in transgenic mice protects against hypertension similar to tempol; d. the role of NADPH oxidase, by measuring p22 phox expression and the effect of apocynin. ..
  69. REGULATION OF SUPEROXIDE PRODUCTION BY HUMAN NEUTROPHILS
    Jeffrey Friedman; Fiscal Year: 2007
    ..These studies may ultimately lead to new pharmacological methods for controlling oxygen radical-mediated tissue damage as well as an improved understanding of the pathophysiology of CGD. ..
  70. NITRIC OXIDE/SUPEROXIDE IN LIPID VASCULAR DISEASE
    TIMOTHY O BRIEN; Fiscal Year: 2000
    ..Specific Aim 3 is to determine the relative roles of eNOS and SOD in cholesterol-induced vasomotor dysfunction. It is hypothesized that co-expression of SOD with eNOS will augment vascular relaxation. ..
  71. NITRIC OXIDE AND SUPEROXIDE INTERACTIONS IN THE PLACENTA
    Leslie Myatt; Fiscal Year: 2002
    ..5. Expression of mRNA and protein for SOD isoforms, xanthine oxidase and the cytochrome b558 subunit of NADPH oxidase in normal and pathologic placental tissues using RT-PCR and immunohistochemistry. ..