sphingomyelin phosphodiesterase

Summary

Summary: An enzyme that catalyzes the hydrolysis of sphingomyelin to ceramide (N-acylsphingosine) plus choline phosphate. A defect in this enzyme leads to NIEMANN-PICK DISEASE. EC 3.1.4.12.

Top Publications

  1. ncbi Ceramide triggers budding of exosome vesicles into multivesicular endosomes
    Katarina Trajkovic
    Centre for Biochemistry and Molecular Cell Biology, University of Gottingen, 37073 Gottingen, Germany
    Science 319:1244-7. 2008
  2. ncbi Endothelial apoptosis as the primary lesion initiating intestinal radiation damage in mice
    F Paris
    Laboratory of Signal Transduction and, Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA
    Science 293:293-7. 2001
  3. ncbi Tumor response to radiotherapy regulated by endothelial cell apoptosis
    Monica Garcia-Barros
    Laboratory of Signal Transduction, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA
    Science 300:1155-9. 2003
  4. pmc Exocytosis of acid sphingomyelinase by wounded cells promotes endocytosis and plasma membrane repair
    Christina Tam
    Section of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06536, USA
    J Cell Biol 189:1027-38. 2010
  5. pmc Deregulation of sphingolipid metabolism in Alzheimer's disease
    Xingxuan He
    Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, NY 10029, USA
    Neurobiol Aging 31:398-408. 2010
  6. ncbi Ceramide in stress response
    Mariana N Nikolova-Karakashian
    Department of Physiology, University of Kentucky College of Medicine, Lexington, Kentucky 40536, USA
    Adv Exp Med Biol 688:86-108. 2010
  7. ncbi Acid sphingomyelinase-deficient human lymphoblasts and mice are defective in radiation-induced apoptosis
    P Santana
    Laboratory of Signal Transduction, Memorial Sloan Kettering Cancer Center New York, New York 10021, USA
    Cell 86:189-99. 1996
  8. ncbi Cisplatin-induced CD95 redistribution into membrane lipid rafts of HT29 human colon cancer cells
    Sandrine Lacour
    Institut National de la Sante et de la Recherche Médicale U517, Dijon, France
    Cancer Res 64:3593-8. 2004
  9. ncbi Ceramide in apoptosis: an overview and current perspectives
    Benjamin J Pettus
    Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC, USA
    Biochim Biophys Acta 1585:114-25. 2002
  10. ncbi Altered adipose and plasma sphingolipid metabolism in obesity: a potential mechanism for cardiovascular and metabolic risk
    Fahumiya Samad
    Division of Vascular Biology, La Jolla Institute for Molecular Medicine, San Diego, CA 92121, USA
    Diabetes 55:2579-87. 2006

Research Grants

  1. Vitamin K and Sulfatides in Brain Aging
    Natalia Crivello; Fiscal Year: 2006
  2. Novel Targets of Rituximab in FSGS
    SANDRA MONIKA MERSCHER; Fiscal Year: 2013
  3. Molecular Genetic Analysis of Lysosomal Storage Disorder Genes in PD
    Lorraine N Clark; Fiscal Year: 2011
  4. Iron Therapy in Renal Disease: Potential Toxicities
    RICHARD ZAGER; Fiscal Year: 2008
  5. LCAT AND PATHOPHYSIOLOGY OF PHOSPHOLIPID SPECIES
    Papasani Subbaiah; Fiscal Year: 2002
  6. ROLE OF SPHINGOMYELIN IN LIPOPROTEIN METABOLISM
    Papasani Subbaiah; Fiscal Year: 2008
  7. ACUTE RENAL FAILURE--IMPACT OF FLUORINATED ANESTHETICS
    RICHARD ZAGER; Fiscal Year: 2001
  8. NEW THERAPEUTICS FOR PATHOGENIC E-COLI DISEASES
    Tom Obrig; Fiscal Year: 2007
  9. SHIGA TOXIN MODE OF ACTION IN BACTERIAL DISEASE
    Tom Obrig; Fiscal Year: 2007
  10. ROLE OF SURFACTANT PROTEIN D IN SURFACTANT HOMEOSTASIS
    Machiko Ikegami; Fiscal Year: 2006

Detail Information

Publications264 found, 100 shown here

  1. ncbi Ceramide triggers budding of exosome vesicles into multivesicular endosomes
    Katarina Trajkovic
    Centre for Biochemistry and Molecular Cell Biology, University of Gottingen, 37073 Gottingen, Germany
    Science 319:1244-7. 2008
    ..Purified exosomes were enriched in ceramide, and the release of exosomes was reduced after the inhibition of neutral sphingomyelinases. These results establish a pathway in intraendosomal membrane transport and exosome formation...
  2. ncbi Endothelial apoptosis as the primary lesion initiating intestinal radiation damage in mice
    F Paris
    Laboratory of Signal Transduction and, Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA
    Science 293:293-7. 2001
    ..This study provides a basis for new approaches to prevent radiation damage to the bowel...
  3. ncbi Tumor response to radiotherapy regulated by endothelial cell apoptosis
    Monica Garcia-Barros
    Laboratory of Signal Transduction, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA
    Science 300:1155-9. 2003
    ..These studies indicate that microvascular damage regulates tumor cell response to radiation at the clinically relevant dose range...
  4. pmc Exocytosis of acid sphingomyelinase by wounded cells promotes endocytosis and plasma membrane repair
    Christina Tam
    Section of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06536, USA
    J Cell Biol 189:1027-38. 2010
    ....
  5. pmc Deregulation of sphingolipid metabolism in Alzheimer's disease
    Xingxuan He
    Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, NY 10029, USA
    Neurobiol Aging 31:398-408. 2010
    ..The reduced levels of S1P in the AD brain, together with elevated ceramide, likely contribute to the disease pathogenesis...
  6. ncbi Ceramide in stress response
    Mariana N Nikolova-Karakashian
    Department of Physiology, University of Kentucky College of Medicine, Lexington, Kentucky 40536, USA
    Adv Exp Med Biol 688:86-108. 2010
    ....
  7. ncbi Acid sphingomyelinase-deficient human lymphoblasts and mice are defective in radiation-induced apoptosis
    P Santana
    Laboratory of Signal Transduction, Memorial Sloan Kettering Cancer Center New York, New York 10021, USA
    Cell 86:189-99. 1996
    ..These genetic models provide definitive evidence for the involvement of acid sphingomyelinase in one form of stress-induced apoptosis...
  8. ncbi Cisplatin-induced CD95 redistribution into membrane lipid rafts of HT29 human colon cancer cells
    Sandrine Lacour
    Institut National de la Sante et de la Recherche Médicale U517, Dijon, France
    Cancer Res 64:3593-8. 2004
    ..Such redistribution contributes to cell death and sensitizes tumor cells to CD95-mediated apoptosis...
  9. ncbi Ceramide in apoptosis: an overview and current perspectives
    Benjamin J Pettus
    Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC, USA
    Biochim Biophys Acta 1585:114-25. 2002
    ....
  10. ncbi Altered adipose and plasma sphingolipid metabolism in obesity: a potential mechanism for cardiovascular and metabolic risk
    Fahumiya Samad
    Division of Vascular Biology, La Jolla Institute for Molecular Medicine, San Diego, CA 92121, USA
    Diabetes 55:2579-87. 2006
    ....
  11. ncbi Absorption and lipoprotein transport of sphingomyelin
    Ake Nilsson
    Department of Medicine, University of Lund, University Hospital, S 22185 Lund, Sweden
    J Lipid Res 47:154-71. 2006
    ..Some SM must be degraded via receptor-mediated catabolism of chylomicron and VLDL remnants and by scavenger receptor class B type I receptor-mediated transfer into cells...
  12. ncbi Functional Inhibitors of Acid Sphingomyelinase (FIASMAs): a novel pharmacological group of drugs with broad clinical applications
    Johannes Kornhuber
    Department of Psychiatry and Psychotherapy, University of Erlangen, Erlangen, Germany
    Cell Physiol Biochem 26:9-20. 2010
    ..Most of the available FIASMAs are licensed for medical use in humans, are minimally toxic and may therefore be applied for disease states associated with increased activity of ASM...
  13. pmc Drug targeting of sphingolipid metabolism: sphingomyelinases and ceramidases
    Daniel Canals
    Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC, USA
    Br J Pharmacol 163:694-712. 2011
    ....
  14. pmc The therapeutic potential of modulating the ceramide/sphingomyelin pathway
    Richard Kolesnick
    Laboratory of Signal Transduction, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA
    J Clin Invest 110:3-8. 2002
  15. ncbi Biological aspects of ceramide-enriched membrane domains
    Heike Grassme
    Institute of Molecular Biology, University of Duisburg Essen, 45122 Essen, Germany
    Prog Lipid Res 46:161-70. 2007
    ..In addition, ceramide directly interacts with and stimulates intracellular enzymes that may act together with signals initiated in ceramide-enriched membrane domains to transmit signals into a cell...
  16. ncbi Cathepsin D links TNF-induced acid sphingomyelinase to Bid-mediated caspase-9 and -3 activation
    M Heinrich
    Institute of Immunology, University of Kiel, Kiel D 24105, Germany
    Cell Death Differ 11:550-63. 2004
    ..Our results link as novel endosomal intermediates the A-SMase and the acid aspartate protease CTSD to the mitochondrial apoptotic TNF pathway...
  17. ncbi Acid sphingomyelinase overexpression enhances the antineoplastic effects of irradiation in vitro and in vivo
    Eric L Smith
    Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, New York 10029, USA
    Mol Ther 16:1565-71. 2008
    ..Based on the data presented in this article, we propose that further investigation of this protein and gene as antineoplastic agents also is warranted...
  18. ncbi Loxosceles sphingomyelinase induces complement-dependent dermonecrosis, neutrophil infiltration, and endogenous gelatinase expression
    Denise V Tambourgi
    Laboratório de Imunoquímica, Instituto Butantan, Sao Paulo, Brazil
    J Invest Dermatol 124:725-31. 2005
    ..Furthermore, skin fibroblasts also secreted MMP-9 and MMP-2 upon incubation with venom, suggesting that locally produced MMPs can also contribute to proteolytic tissue destruction...
  19. ncbi Small molecule inhibitors of acid sphingomyelinase
    Christoph Arenz
    Institut fur Chemie, Humboldt Universitat zu Berlin, Berlin, Germany
    Cell Physiol Biochem 26:1-8. 2010
    ..Very recently, some new and promising inhibitors from different substance classes have been developed. In this review, previous and current developments in the field are summarized...
  20. ncbi Biochemical properties of mammalian neutral sphingomyelinase 2 and its role in sphingolipid metabolism
    Norma Marchesini
    Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston 29425, USA
    J Biol Chem 278:13775-83. 2003
    ..In conclusion, these results 1) show that nSMase2 is a structural gene for nSMase, 2) suggest that nSMase2 acts as a bona fide N-SMase in cells, and 3) implicate nSMase2 in the regulation of cell growth and cell signaling...
  21. pmc The unconventional role of acid sphingomyelinase in regulation of retinal microangiopathy in diabetic human and animal models
    Madalina Opreanu
    Department of Physiology, Michigan State University, East Lansing, Michigan, USA
    Diabetes 60:2370-8. 2011
    ..The role of ASM in retinal vascular inflammation and vessel loss associated with diabetic retinopathy is not known and represents the goal of this study...
  22. ncbi The roles of neutral sphingomyelinases in neurological pathologies
    Charles R Horres
    Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC, USA
    Neurochem Res 37:1137-49. 2012
    ....
  23. ncbi Phospholipases C and sphingomyelinases: Lipids as substrates and modulators of enzyme activity
    Felix M Goni
    Unidad de Biofisica, Centro Mixto CSIC UPV EHU, Universidad del Pais Vasco, Aptdo 644, 48080 Bilbao, Spain
    Prog Lipid Res 51:238-66. 2012
    ....
  24. pmc Niemann-Pick disease: a frequent missense mutation in the acid sphingomyelinase gene of Ashkenazi Jewish type A and B patients
    O Levran
    Division of Medical and Molecular Genetics, Mount Sinai School of Medicine, New York, NY 10029
    Proc Natl Acad Sci U S A 88:3748-52. 1991
    ..The identification of this ASM mutation in Ashkenazi Jewish patients should facilitate the prevention of NPD in this population by carrier detection with molecular diagnostic techniques...
  25. ncbi Ceramide metabolism is affected by obesity and diabetes in human adipose tissue
    A U Błachnio-Zabielska
    Department of Physiology, Medical University of Bialystok, Białystok, Poland
    J Cell Physiol 227:550-7. 2012
    ..67, P < 0.001). We have found that both obesity and diabetes affected pathways of sphingolipid metabolism in the adipose tissue...
  26. ncbi Neonatal screening for lysosomal storage disorders: feasibility and incidence from a nationwide study in Austria
    Thomas P Mechtler
    Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria
    Lancet 379:335-41. 2012
    ....
  27. pmc Identification of factors contributing to T-cell toxicity of Staphylococcus aureus clinical isolates
    James Collins
    Department of Zoology, University of Oxford, Oxford OX1 3PS, United Kingdom
    J Clin Microbiol 46:2112-4. 2008
    ..We found that the beta and delta hemolysins are involved and that methicillin-resistant S. aureus strains are less toxic than methicillin-susceptible S. aureus strains...
  28. pmc Identification of novel functional inhibitors of acid sphingomyelinase
    Johannes Kornhuber
    Department of Psychiatry and Psychotherapy, University of Erlangen, Erlangen, Germany
    PLoS ONE 6:e23852. 2011
    ..Virtual screening revealed that only six out of 768 (0.78%) compounds of natural products functionally inhibit ASM, whereas this inhibitory activity occurs in 135 out of 2028 (6.66%) drugs licensed for medical use in humans...
  29. pmc The demographics and distribution of type B Niemann-Pick disease: novel mutations lead to new genotype/phenotype correlations
    Calogera M Simonaro
    Department of Human Genetics, Mount Sinai School of Medicine, New York, NY 10029, USA
    Am J Hum Genet 71:1413-9. 2002
    ..These data provide the first extensive demographic assessment of this disorder and describe several new mutations that can be used to predict phenotypic outcome and to gain new insights into the structure and function of ASM...
  30. pmc Niemann-Pick type B disease. Identification of a single codon deletion in the acid sphingomyelinase gene and genotype/phenotype correlations in type A and B patients
    O Levran
    Division of Medical and Molecular Genetics, Mount Sinai School of Medicine, New York, New York 10029
    J Clin Invest 88:806-10. 1991
    ..Although only two patients have been studied, it appears that the delta R608 mutation occurs frequently in Type B Niemann-Pick disease patients of Ashkenazi Jewish descent...
  31. pmc Degradation of host sphingomyelin is essential for Leishmania virulence
    Ou Zhang
    Department of Biological Sciences, Texas Tech University, Lubbock, Texas, USA
    PLoS Pathog 5:e1000692. 2009
    ..Together, these findings strongly suggest that degradation of host-derived sphingomyelin plays a pivotal role in the proliferation of Leishmania in mammalian hosts and the manifestation of acute disease pathology...
  32. ncbi The pathogenesis and treatment of acid sphingomyelinase-deficient Niemann-Pick disease
    E H Schuchman
    Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, NY 10029, USA
    Int J Clin Pharmacol Ther 47:S48-57. 2009
    ..Based on these studies, clinical trials of ERT are underway in patients with non-neurological ASM-deficient NPD...
  33. ncbi Secretory sphingomyelinase is upregulated in chronic heart failure: a second messenger system of immune activation relates to body composition, muscular functional capacity, and peripheral blood flow
    Wolfram Doehner
    Division of Applied Cachexia Research, Department of Cardiology, Charite Medical School, Campus Virchow Klinikum, Berlin, Germany
    Eur Heart J 28:821-8. 2007
    ....
  34. pmc Gilenya (FTY720) inhibits acid sphingomyelinase by a mechanism similar to tricyclic antidepressants
    Glyn Dawson
    Department of Pediatrics, University of Chicago, Chicago, IL 60637, USA
    Biochem Biophys Res Commun 404:321-3. 2011
    ....
  35. pmc Withanolide D induces apoptosis in leukemia by targeting the activation of neutral sphingomyelinase-ceramide cascade mediated by synergistic activation of c-Jun N-terminal kinase and p38 mitogen-activated protein kinase
    Susmita Mondal
    Infectious Diseases and Immunology Division, Indian Institute of Chemical Biology, A Unit of Council of Scientific and Industrial Research, Govt, of India 4, Raja S, C, Mullick Road, Kolkata 700032, India
    Mol Cancer 9:239. 2010
    ..Manipulation in ceramide production by physiological and pharmacological modulators therefore will give additive effect in leukemia chemotherapy...
  36. ncbi Ceramide-mediated clustering is required for CD95-DISC formation
    Heike Grassme
    Department of Molecular Biology, University of Duisburg Essen, Hufelandstrasse 55, 45122 Essen, Germany
    Oncogene 22:5457-70. 2003
    ....
  37. ncbi Plasma sphingomyelin level as a risk factor for coronary artery disease
    X C Jiang
    Department of Medicine, Columbia University, New York, NY 10032, USA
    Arterioscler Thromb Vasc Biol 20:2614-8. 2000
    ..Plasma SM levels could be a marker for atherogenic remnant lipoprotein accumulation and may predict lipoprotein susceptibility to arterial wall sphingomyelinase...
  38. pmc Roles for tumor necrosis factor receptor p55 and sphingomyelinase in repairing the cutaneous permeability barrier
    J M Jensen
    Department of Dermatology, and Institute of Immunology, University of Kiel, 24105 Kiel, Germany
    J Clin Invest 104:1761-70. 1999
    ..Together, these results suggest that TNF-R55 signaling pathways contribute to cutaneous permeability barrier repair through SMase-mediated generation of ceramide...
  39. ncbi Acid sphingomyelinase deficient mice: a model of types A and B Niemann-Pick disease
    K Horinouchi
    Department of Human Genetics, Mount Sinai School of Medicine, New York, New York 10029, USA
    Nat Genet 10:288-93. 1995
    ..Thus, the ASM deficient mice should be of great value for studying the pathogenesis and treatment of NPD, and for investigations into the role of ASM in signal transduction and apoptosis...
  40. ncbi Zn2+-stimulated sphingomyelinase is secreted by many cell types and is a product of the acid sphingomyelinase gene
    S L Schissel
    Department of Anatomy, Columbia University, New York, New York 10032, USA
    J Biol Chem 271:18431-6. 1996
    ..This secreted enzyme may play roles in physiological and pathophysiological processes involving extracellular sphingomyelin hydrolysis...
  41. pmc A critical role for ceramide synthase 2 in liver homeostasis: I. alterations in lipid metabolic pathways
    Yael Pewzner-Jung
    Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel
    J Biol Chem 285:10902-10. 2010
    ..Together, these results demonstrate novel modes of cross-talk and regulation between the various branches of lipid metabolic pathways upon inhibition of very long acyl chain ceramide synthesis...
  42. pmc Structure and biological activities of beta toxin from Staphylococcus aureus
    Medora Huseby
    Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minnesota, USA
    J Bacteriol 189:8719-26. 2007
    ..Structure-directed active site mutations show that biological activities, including hemolysis and lymphotoxicity, are due to the sphingomyelinase activity of the enzyme...
  43. pmc Mammalian neutral sphingomyelinases: regulation and roles in cell signaling responses
    Bill X Wu
    Department of Biochemistry and Molecular Biology, Medical University of South Carolina, 173 Ashley Ave, Charleston, SC 29425, USA
    Neuromolecular Med 12:320-30. 2010
    ..In this review, we summarize recent findings for the cloned nSMases and discuss the insights for their roles in regulation ceramide metabolism and cellular signaling pathway...
  44. pmc The neutral sphingomyelinase family: identifying biochemical connections
    Christopher J Clarke
    Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 29425, USA
    Adv Enzyme Regul 51:51-8. 2011
    ..With this in mind, we sincerely hope that the next decade of research will even surpass the last ten years in advancing our understanding of the eukaryotic N-SMase family...
  45. ncbi Acid sphingomyelinase inhibitors normalize pulmonary ceramide and inflammation in cystic fibrosis
    Katrin Anne Becker
    Professor and Chair, Department of Molecular Biology, University of Duisburg Essen, Hufelandstrasse 55, D 45122 Essen, Germany
    Am J Respir Cell Mol Biol 42:716-24. 2010
    ..Inhaling an Asm inhibitor may be a beneficial treatment for CF, with minimal adverse systemic effects...
  46. pmc Roles and regulation of secretory and lysosomal acid sphingomyelinase
    Russell W Jenkins
    Department of Biochemistry and Molecular Biology, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, USA
    Cell Signal 21:836-46. 2009
    ..How a single gene product has the capacity to function in these diverse settings, and the subsequent impact on downstream ceramide-mediated biology is the subject of this review...
  47. ncbi p53-Independent ceramide formation in human glioma cells during gamma-radiation-induced apoptosis
    S Hara
    Department of Neurosurgery, Gifu University School of Medicine, Tsukasamachi 40, Gifu 500 8705, Japan
    Cell Death Differ 11:853-61. 2004
    ....
  48. pmc Acid sphingomyelinase activity triggers microparticle release from glial cells
    Fabio Bianco
    CNR Institute of Neuroscience and Department of Medical Pharmacology, University of Milano, Milano, Italy
    EMBO J 28:1043-54. 2009
    ....
  49. ncbi Bax and Bak do not exhibit functional redundancy in mediating radiation-induced endothelial apoptosis in the intestinal mucosa
    Jimmy A Rotolo
    Laboratory of Signal Transduction, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Int J Radiat Oncol Biol Phys 70:804-15. 2008
    ..To address in vivo the issue of whether Bax and Bak are functionally redundant in signaling apoptosis, capable of substituting for each other...
  50. pmc Protection from high fat diet-induced increase in ceramide in mice lacking plasminogen activator inhibitor 1
    Charmi Shah
    Torrey Pines Institute for Molecular Studies, San Diego, California 92121, USA
    J Biol Chem 283:13538-48. 2008
    ..This study has identified a novel link between sphingolipid metabolism and PAI-1 and also suggests that ceramide may be an intermediary molecule linking elevated PAI-1 to insulin resistance...
  51. ncbi Fusogenicity of membranes: the impact of acid sphingomyelinase on innate immune responses
    Olaf Utermöhlen
    Institute for Medical Microbiology, Immunology and Hygiene, Medical Center, University of Cologne, Goldenfelsstrasse 19 21, 50935 Cologne, Germany
    Immunobiology 213:307-14. 2008
    ..In light of the biochemical and biophysical properties of ceramide, we provide a model suggesting that ASMase regulates select vesicular fusion processes by modifying the steric conformation of cellular membranes...
  52. ncbi The extended family of neutral sphingomyelinases
    Christopher J Clarke
    Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, South Carolina 29425, USA
    Biochemistry 45:11247-56. 2006
    ..We also briefly consider the major future directions for N-SMase research which promises highly significant and specific insight into sphingolipid-mediated functions...
  53. pmc Lack of ceramide generation and altered sphingolipid composition are associated with drug resistance in human ovarian carcinoma cells
    Alessandro Prinetti
    Centre of Excellence for Neurodegenerative Disease, Department of Medical Chemistry, Biochemistry and Biotechnology, University of Milan, 20090 Segrate, Italy
    Biochem J 395:311-8. 2006
    ....
  54. ncbi Acid sphingomyelinase: identification of nine novel mutations among Italian Niemann Pick type B patients and characterization of in vivo functional in-frame start codon
    M G Pittis
    Unita di Malattie Metaboliche, I R C C S Burlo Garofolo, Trieste, Italy
    Hum Mutat 24:186-7. 2004
    ..96G>A (p.W32X), the most frequent allele among Italian NPD type B population, and c.1799G>C (p.R600P) as compound heterozygotes in association with severe mutations suggested a beneficial effect for both mutations...
  55. pmc Anti-ceramide antibody prevents the radiation gastrointestinal syndrome in mice
    Jimmy Rotolo
    Laboratory of Signal Transduction, Memorial Sloan Kettering Cancer Center MSKCC, New York, New York, USA
    J Clin Invest 122:1786-90. 2012
    ..As such, we suggest that 2A2 represents a prototype of a new class of anti-ceramide therapeutics and an effective countermeasure against radiation GI syndrome mortality...
  56. pmc Staphylococcus aureus hijacks a skin commensal to intensify its virulence: immunization targeting β-hemolysin and CAMP factor
    Chih Wei Lo
    Division of Dermatology, Department of Medicine, University of California, San Diego, San Diego, California 92121, USA
    J Invest Dermatol 131:401-9. 2011
    ..acnes and S. aureus. These observations suggest a previously unreported immunotherapy targeting the interaction of S. aureus with a skin commensal...
  57. ncbi Screening of 25 Italian patients with Niemann-Pick A reveals fourteen new mutations, one common and thirteen private, in SMPD1
    V Ricci
    Laboratorio Diagnosi Pre Postnatale Malattie Metaboliche, University of Genoa, Istituto G Gaslini, Genova, Italy
    Hum Mutat 24:105. 2004
    ..However, new genotype/phenotype correlations were observed for this disorder that could in the future facilitate genetic counseling and guide selection of patients for therapy...
  58. ncbi nSMase2 activation and trafficking are modulated by oxidative stress to induce apoptosis
    Michal Levy
    Signal Transduction Laboratory, Department of Internal Medicine, University of California, School of Medicine, Davis, CA 95616, USA
    Biochem Biophys Res Commun 344:900-5. 2006
    ..On the other hand, exposure to GSH results in nSMase2 trafficking to the nucleus, where it neither generates ceramide nor induces apoptosis...
  59. pmc Role of sphingomyelinase in infectious diseases caused by Bacillus cereus
    Masataka Oda
    Department of Microbiology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Yamashiro cho, Tokushima, Japan
    PLoS ONE 7:e38054. 2012
    ..The results suggest that Bc-SMase is essential for the hydrolysis of SM in membranes, leading to a reduction in phagocytosis...
  60. ncbi Increased acid sphingomyelinase activity in peripheral blood cells of acutely intoxicated patients with alcohol dependence
    Martin Reichel
    Department of Psychiatry and Psychotherapy, University of Erlangen, Erlangen, Germany
    Alcohol Clin Exp Res 34:46-50. 2010
    ..Ethanol-induced activation of ASM has been observed in different cell culture systems, thus raising the question about the effect of alcohol intoxication in human subjects on ASM activity in vivo...
  61. pmc Syntaxin 4 is required for acid sphingomyelinase activity and apoptotic function
    Cristiana Perrotta
    Unit of Clinical Pharmacology, Department of Clinical Sciences, University Hospital Luigi Sacco, Universita degli Studi di Milano, 20157 Milan, Italy
    J Biol Chem 285:40240-51. 2010
    ..The novel actions of syntaxin 4 in sphingolipid metabolism and exocytosis we describe here define signaling mechanisms of broad relevance in cell pathophysiology...
  62. pmc Brain pathology in Niemann Pick disease type A: insights from the acid sphingomyelinase knockout mice
    Maria Dolores Ledesma
    Centro Biologia Molecular Severo Ochoa CSIC UAM, Madrid, Spain
    J Neurochem 116:779-88. 2011
    ..Some of these have already been tested in mice lacking ASM with promising results...
  63. pmc Mutations in the neutral sphingomyelinase gene SMPD3 implicate the ceramide pathway in human leukemias
    Woo Jae Kim
    Massachusetts General Hospital Cancer Center, Boston, MA, USA
    Blood 111:4716-22. 2008
    ..Taken together, these observations suggest that disruption of the ceramide pathway may contribute to a subset of human leukemias...
  64. ncbi Delivery of acid sphingomyelinase in normal and niemann-pick disease mice using intercellular adhesion molecule-1-targeted polymer nanocarriers
    Carmen Garnacho
    Department of Pharmacology, John Morgan Bldg, 3620 Hamilton Walk, Philadelphia, PA 19104 6068, USA
    J Pharmacol Exp Ther 325:400-8. 2008
    ..These data demonstrate that ICAM-1-targeted nanocarriers may enhance enzyme replacement therapy for type B NPD and perhaps other lysosomal storage disorders...
  65. pmc Sphingomyelin phosphodiesterase-1 (SMPD1) coding variants do not contribute to low levels of high-density lipoprotein cholesterol
    Zari Dastani
    Cardiovascular Research Laboratories, Division of Cardiology, McGill University Health Centre Royal Victoria Hospital, Montreal, Quebec H3A 1A1, Canada
    BMC Med Genet 8:79. 2007
    ..disease type A and B is caused by a deficiency of acid sphingomyelinase due to mutations in the sphingomyelin phosphodiesterase-1 (SMPD1) gene...
  66. ncbi Acid sphingomyelinase and its redox amplification in formation of lipid raft redox signaling platforms in endothelial cells
    Andrew Y Zhang
    Department of Pharmacology and Toxicology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA 23298, USA
    Antioxid Redox Signal 9:817-28. 2007
    ..This ASM-mediated feedforwarding mechanism may be critical for an efficient transmembrane signaling through LRs...
  67. pmc Free insulin-like growth factor binding protein-3 (IGFBP-3) reduces retinal vascular permeability in association with a reduction of acid sphingomyelinase (ASMase)
    Jennifer L Kielczewski
    Departments of Pharmacology and Therapeutics, University of Florida, Gainesville, Florida 32610 0267, USA
    Invest Ophthalmol Vis Sci 52:8278-86. 2011
    ..To examine the effect of free insulin-like growth factor (IGF) binding protein-3 (IGFBP-3), independent of the effect of insulin-like growth factors, in modulating retinal vascular permeability...
  68. ncbi Endoplasmic reticulum stress-mediated inhibition of NSMase2 elevates plasma membrane cholesterol and attenuates NO production in endothelial cells
    Ruchi Chaube
    Department of Chemistry and Biochemistry, University of Windsor, Windsor, ON, Canada
    Biochim Biophys Acta 1821:313-23. 2012
    ..This study establishes NSMase2 as a pivotal enzyme in the onset of endothelial ER stress-mediated vascular dysfunction as its inactivation leads to the attenuation of NO production and the elevation of cellular cholesterol...
  69. pmc Identification and characterization of eight novel SMPD1 mutations causing types A and B Niemann-Pick disease
    Jonathan P Desnick
    Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine of New York University, New York, New York 10029, United States of America
    Mol Med 16:316-21. 2010
    ..NPD) result from the deficient activity of acid sphingomyelinase (ASM), due to mutations in the sphingomyelin phosphodiesterase 1 (SMPD1) gene...
  70. ncbi Seven novel acid sphingomyelinase gene mutations in Niemann-Pick type A and B patients
    J Sikora
    Institute of Inherited Metabolic Disorders, Charles University, 1st Faculty of Medicine, Prague, Czech Republic
    Ann Hum Genet 67:63-70. 2003
    ..Geographical and/or social isolation of the affected families are likely contributing factors for the high number of homozygotes in our group...
  71. pmc Familial adenomatous polyposis is associated with a marked decrease in alkaline sphingomyelinase activity: a key factor to the unrestrained cell proliferation?
    E Hertervig
    Department of Medicine, Lund University Hospital, Sweden
    Br J Cancer 81:232-6. 1999
    ..We conclude that the markedly reduced levels of alkaline sphingomyelinase activities in FAP adenomas and in the surrounding mucosa may be a pathogenic factor that can lead to unrestrained cell proliferation and neoplastic transformation...
  72. ncbi Requirement of FADD for tumor necrosis factor-induced activation of acid sphingomyelinase
    K Wiegmann
    Institute of Immunology, University of Kiel, 24105 Kiel, Germany
    J Biol Chem 274:5267-70. 1999
    ..The results of this study suggest that FADD, in addition to its role in triggering a proapoptotic caspase cascade, is required for TNF-induced activation of A-SMase...
  73. ncbi Identification of human intestinal alkaline sphingomyelinase as a novel ecto-enzyme related to the nucleotide phosphodiesterase family
    Rui Dong Duan
    Gastroenterology Laboratory, Biomedical Center, B11, Lund University, S 221 84 Lund, Sweden
    J Biol Chem 278:38528-36. 2003
    ..In conclusion, we identified the amino acid and cDNA sequences of human intestinal alk-SMase, and found that it is a novel ecto-enzyme related to the NPP family with specific features essential for its SMase activity...
  74. ncbi Activation of human acid sphingomyelinase through modification or deletion of C-terminal cysteine
    Huawei Qiu
    Cell and Protein Therapeutics R and D Department, Genzyme Corp, Framingham, Massachusetts 01701, USA
    J Biol Chem 278:32744-52. 2003
    ..This method of activation is similar to the cysteine switch mechanism described previously for matrix metalloproteinases and could represent a means of posttranslational regulation of ASM activity in vivo...
  75. pmc Defective TNF-alpha-mediated hepatocellular apoptosis and liver damage in acidic sphingomyelinase knockout mice
    Carmen Garcia-Ruiz
    Liver Unit, Instituto de Malalties Digestives, Hospital Clinic i Provincial, Instituto de Investigaciones Biomédicas August Pi Suñer, Barcelona, Spain
    J Clin Invest 111:197-208. 2003
    ..Thus, ASMase contributes to TNF-alpha-induced hepatocellular apoptosis by promoting the mitochondrial targeting of glycosphingolipids...
  76. pmc Lipopolysaccharide induces disseminated endothelial apoptosis requiring ceramide generation
    A Haimovitz-Friedman
    Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York 10021, USA
    J Exp Med 186:1831-41. 1997
    ..These investigations demonstrate that LPS induces a disseminated form of endothelial apoptosis, mediated sequentially by TNF and ceramide generation, and suggest that this cascade is mandatory for evolution of the endotoxic syndrome...
  77. pmc The unexpected role of acid sphingomyelinase in cell death and the pathophysiology of common diseases
    Eric L Smith
    Department of Genetics and Genomic Sciences, Mt Sinai School of Medicine, 1425 Madison Ave, New York, NY 10029, USA
    FASEB J 22:3419-31. 2008
    ....
  78. ncbi A fluorescence-based, high-performance liquid chromatographic assay to determine acid sphingomyelinase activity and diagnose types A and B Niemann-Pick disease
    Xingxuan He
    Department of Human Genetics, Mount Sinai School of Medicine, New York, NY 10029, USA
    Anal Biochem 314:116-20. 2003
    Acid sphingomyelinase (ASM; sphingomyelin phosphodiesterase, EC 3.1.4.12) is the lysosomal enzyme that hydrolyzes sphingomyelin (SPM) to phosphorylcholine and ceramide...
  79. pmc Isolation of cDNA clones encoding human acid sphingomyelinase: occurrence of alternatively processed transcripts
    L E Quintern
    Institut für Organische Chemie und Biochemie der Universitat Bonn FRG
    EMBO J 8:2469-73. 1989
    Acid sphingomyelinase (sphingomyelin phosphodiesterase, EC 3.1.4.12) was purified from human urine and 12 tryptic peptides were microsequenced (128 residues)...
  80. ncbi Hemolysis induced by Bacillus cereus sphingomyelinase
    Masataka Oda
    Department of Microbiology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Yamashiro cho, Tokushima, Japan 770 8514
    Biochim Biophys Acta 1798:1073-80. 2010
    ..These results show that Bc-SMase-induced hemolysis of sheep erythrocytes is related to the formation of interface between ceramide-rich domains and ceramide-poor domains through production of ceramide from SM...
  81. ncbi Highly variable neural involvement in sphingomyelinase-deficient Niemann-Pick disease caused by an ancestral Gypsy mutation
    Violeta Mihaylova
    Department of Neurology, Medical University, Sofia, Bulgaria
    Brain 130:1050-61. 2007
    Niemann-Pick disease (NPD), an autosomal recessive disorder resulting from mutations in the sphingomyelin phosphodiesterase 1 (SMPD1) gene, is subdivided into the acute, lethal neuronopathic type A, and the chronic visceral type B, ..
  82. ncbi Integrin alpha(v)beta(3), metalloproteinases, and sphingomyelinase-2 mediate urokinase mitogenic effect
    Françoise Maupas-Schwalm
    Inserm U858 Team 10, Dept of Biochemistry and Molecular Biology, Faculty of Medicine Rangueil, University Paul Sabatier Toulouse 3, IFR 150, Toulouse, France
    Cell Signal 21:1925-34. 2009
    ..These findings highlight a new signaling mechanism for uPA, and suggest that, upon uPA stimulation, uPAR, MMPs, integrin alpha(v)beta(3) and NSMase-2 form a signaling complex that take part in mitogenic signaling in ECV304 cells...
  83. pmc The essential neutral sphingomyelinase is involved in the trafficking of the variant surface glycoprotein in the bloodstream form of Trypanosoma brucei
    Simon A Young
    Biomolecular Science, The North Haugh, The University, St Andrews, Fife Scotland KY16 9ST, UK
    Mol Microbiol 76:1461-82. 2010
    ....
  84. ncbi Acid sphingomyelinase is a key regulator of cytotoxic granule secretion by primary T lymphocytes
    Jasmin Herz
    Institute for Medical Microbiology, Immunology and Hygiene, Medical Center, University of Cologne, Germany
    Nat Immunol 10:761-8. 2009
    ..In ASMase-KO CD8+ T cells, the contraction of secretory granules was markedly impaired. Thus, ASMase is required for contraction of secretory granules and expulsion of cytotoxic effector molecules...
  85. pmc Acid Sphingomyelinase Deficiency Prevents Diet-induced Hepatic Triacylglycerol Accumulation and Hyperglycemia in Mice
    Gergana M Deevska
    Departments of Physiology, Pediatrics, and Internal Medicine, University of Kentucky College of Medicine, Lexington, Kentucky 40536, USA
    J Biol Chem 284:8359-68. 2009
    ....
  86. pmc Fibrillar amyloid-beta-activated human astroglia kill primary human neurons via neutral sphingomyelinase: implications for Alzheimer's disease
    Arundhati Jana
    Department of Neurological Science, Rush University Medical Center, Chicago, Illinois 60612, USA
    J Neurosci 30:12676-89. 2010
    ..Together, it is apparent that both the activation of astroglia by Aβ and that the cytotoxicity of activated astroglia on neurons depend on N-SMase...
  87. pmc A Bacillus cereus cytolytic determinant, cereolysin AB, which comprises the phospholipase C and sphingomyelinase genes: nucleotide sequence and genetic linkage
    M S Gilmore
    Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City 73190
    J Bacteriol 171:744-53. 1989
    ..subtilis host. The 3' open reading frame encoded a sphingomyelinase. The two tandemly encoded activities, phospholipase C and sphingomyelinase, constitute a biologically functional cytolytic determinant of B. cereus termed cereolysin AB...
  88. pmc Identification of novel anionic phospholipid binding domains in neutral sphingomyelinase 2 with selective binding preference
    Bill X Wu
    Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, South Carolina 29425, USA
    J Biol Chem 286:22362-71. 2011
    ..The analysis of interactions between nSMase2 and APLs will contribute to our understanding of signaling pathways mediated by sphingolipid metabolites...
  89. pmc Acid sphingomyelinase deficiency attenuates bleomycin-induced lung inflammation and fibrosis in mice
    Rajwinder Dhami
    Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, NY 10029, USA
    Cell Physiol Biochem 26:749-60. 2010
    ..Here we used the bleomycin model of pulmonary fibrosis to investigate fibrotic responses in normal and ASM knockout (ASM(-/-)) mice, and in NIH3T3 fibroblasts with and without ASM siRNA treatment...
  90. ncbi Lipid raft-dependent activation of dual oxidase 1/H2O2/NF-κB pathway in bronchial epithelial cells
    Lifen Wang
    Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
    Am J Physiol Cell Physiol 301:C171-80. 2011
    ..Our results for the first time demonstrate that Duox1-mediated redox signaling in bronchial epithelial cells is associated with LR clustering dependent on the production of ceramide through ASMase...
  91. pmc Sphingomyelin synthase 2 is one of the determinants for plasma and liver sphingomyelin levels in mice
    Jing Liu
    Department of Anatomy and Cell Biology, State University of New York Downstate Medical Center, 450 Clarkson Ave, Box 5, Brooklyn, NY 11203, USA
    Arterioscler Thromb Vasc Biol 29:850-6. 2009
    ..Sphingomyelin synthase (SMS) is the last enzyme for SM de novo biosynthesis. Two SMS genes, SMS1 and SMS2, have been cloned and characterized...
  92. pmc A potent sphingomyelinase inhibitor from Cordyceps mycelia contributes its cytoprotective effect against oxidative stress in macrophages
    Shwu Huey Wang
    Graduate Institute of Medical Sciences, Taipei Medical University, Taipei, Taiwan, Republic of China
    J Lipid Res 52:471-9. 2011
    ..7 cells. Results suggest that CME-1 protects RAW264.7 cells against oxidative stress through inhibition of SMase activity and reduction of C16- and C18-ceramide levels...
  93. pmc Acidic sphingomyelinase controls hepatic stellate cell activation and in vivo liver fibrogenesis
    Anna Moles
    Liver Unit, Hospital Clinic, Centre d Investigació Biomèdica Esther Koplowitz, Centro de Investigación Biomédicas en Red en el Area temática de Enfermedades Hepáticas y Digestivas, Barcelona, Spain
    Am J Pathol 177:1214-24. 2010
    ..These findings illustrate a novel role of ASMase in HSC biology and liver fibrogenesis by regulating its downstream effectors CtsB/D...
  94. pmc Increase in sphingolipid catabolic enzyme activity during aging
    Santosh J Sacket
    Laboratories of Pharmacology, College of Pharmacy BK21 Project and Longevity Institute of Life Science and Technology, Pusan National University, Busan 609 735, Republic of Korea
    Acta Pharmacol Sin 30:1454-61. 2009
    ..To understand the contribution of sphingolipid metabolism and its metabolites to development and aging...
  95. pmc Acid sphingomyelinase in macrophage biology
    Jean Philip Truman
    Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC 29425, USA
    Cell Mol Life Sci 68:3293-305. 2011
    ..We also address the importance of ASMase to several disease processes that are mediated by activated macrophages...
  96. ncbi Lactosylceramide is required in apoptosis induced by N-Smase
    Sergio F Martin
    Lipid Research Atherosclerosis Division, Johns Hopkins University, Baltimore, Maryland, USA
    Glycoconj J 23:147-57. 2006
    ..But it is not sufficient to induce apoptosis. Rather, the conversion of ceramide to LacCer and ROS generation are critical for apoptosis...
  97. ncbi Reactive nitrogen and oxygen species activate different sphingomyelinases to induce apoptosis in airway epithelial cells
    S Sianna Castillo
    Signal Transduction, UC Davis, Genome Biomedical Sciences Facility 451 E Health Sciences Dr, Davis, CA 95616, USA
    Exp Cell Res 313:2680-6. 2007
    ..These findings add to the complexity of how oxidative stress promotes lung cell injury...
  98. ncbi CD95-mediated apoptosis in vivo involves acid sphingomyelinase
    S Kirschnek
    Department of Physiology, University of Tuebingen, Gmelinstrasse 5, Germany
    J Biol Chem 275:27316-23. 2000
    ..Likewise, ASM-deficient mice or hepatocytes and splenocytes ex vivo manifest resistance to anti-CD95 treatment. These results provide in vivo evidence for an important physiological function of ASM in CD95-induced apoptosis...
  99. ncbi Sphingomyelin/cholesterol ratio: an important determinant of glucose transport mediated by GLUT-1 in 3T3-L1 preadipocytes
    Nehmann Al-Makdissy
    Laboratoire de Nutrition et Maladies Métaboliques, EA 3446, Faculte de Medecine, Universite Henri Poincare Nancy 1, BP 184, 54505 Vandoeuvre Les Nancy Cedex, France
    Cell Signal 15:1019-30. 2003
    ..The SM/CL ratio might represent an important parameter controlling basal glucose uptake and a mechanism by which insulin resistance might be induced...
  100. pmc Studies on the role of acid sphingomyelinase and ceramide in the regulation of tumor necrosis factor alpha (TNFalpha)-converting enzyme activity and TNFalpha secretion in macrophages
    Krasimira A Rozenova
    Department of Physiology, University of Kentucky College of Medicine, Lexington, KY 40536, USA
    J Biol Chem 285:21103-13. 2010
    ....
  101. ncbi Pivotal role for acidic sphingomyelinase in cerebral ischemia-induced ceramide and cytokine production, and neuronal apoptosis
    Z F Yu
    Sanders Brown Research Center on Aging, University of Kentucky, Lexington 40536, USA
    J Mol Neurosci 15:85-97. 2000
    ....

Research Grants46

  1. Vitamin K and Sulfatides in Brain Aging
    Natalia Crivello; Fiscal Year: 2006
    ..These studies will provide the foundation for future studies on the role of dietary vitamin K in sphingolipid metabolism as it relates to healthy aging, and ultimately its role in motor and cognitive behavior. [unreadable] [unreadable]..
  2. Novel Targets of Rituximab in FSGS
    SANDRA MONIKA MERSCHER; Fiscal Year: 2013
    ..Finally, our in vitro assay treating normal human podocytes with patient sera may become a pre-transplant assessment test for the identifications of patients at high-risk. ..
  3. Molecular Genetic Analysis of Lysosomal Storage Disorder Genes in PD
    Lorraine N Clark; Fiscal Year: 2011
    ..gene and other lysosomal genes in the same biochemical pathway including Hexosaminidase A (HEXA), Sphingomyelin phosphodiesterase 1 (SMPD1) and mucolipin 1 (MCOLN1) may disrupt the cellular processing and trafficking of a-Synuclein ..
  4. Iron Therapy in Renal Disease: Potential Toxicities
    RICHARD ZAGER; Fiscal Year: 2008
    ..Potential reasons for these differences will be assessed, with the ultimate goal of defining the safest way of administering parenteral irons to renal disease patients. ..
  5. LCAT AND PATHOPHYSIOLOGY OF PHOSPHOLIPID SPECIES
    Papasani Subbaiah; Fiscal Year: 2002
    ..These studies should provide novel insights into the physiological importance of LCAT beyond its role in cholesterol esterification. ..
  6. ROLE OF SPHINGOMYELIN IN LIPOPROTEIN METABOLISM
    Papasani Subbaiah; Fiscal Year: 2008
    ..These studies will provide novel insights into the physiological role of this important phospholipid, and could possibly open up novel therapeutic targets against inflammation and atherosclerosis. ..
  7. ACUTE RENAL FAILURE--IMPACT OF FLUORINATED ANESTHETICS
    RICHARD ZAGER; Fiscal Year: 2001
    ....
  8. NEW THERAPEUTICS FOR PATHOGENIC E-COLI DISEASES
    Tom Obrig; Fiscal Year: 2007
    ..coli 0157:H7-associated disease will be further defined using A2A receptor deficient mice and adoptive bone marrow transfer to determine the role of circulating inflammatory cells in this disease. [unreadable] [unreadable]..
  9. SHIGA TOXIN MODE OF ACTION IN BACTERIAL DISEASE
    Tom Obrig; Fiscal Year: 2007
    ..The goal of these studies is to reveal the opportunities available for effective application of therapeutic agents in STEC-associated renal disease. ..
  10. ROLE OF SURFACTANT PROTEIN D IN SURFACTANT HOMEOSTASIS
    Machiko Ikegami; Fiscal Year: 2006
    ..The intended studies will provide fundamental insights into the role of SP-D in the protection of the lung, as well as into the basic mechanisms determining surfactant homeostasis. ..
  11. Regulation of Transepithelial Transport in PKD
    Rajeev Rohatgi; Fiscal Year: 2008
    ..SA II: To identify those factors that regulate the avid Na absorption seen in ARPKD cyst lining epithelial cells. ..
  12. Brain tumor angiogenesis: Integrin ceramide signaling
    Anat Erdreich Epstein; Fiscal Year: 2008
    ..abstract_text> ..
  13. SCIEX 4000 QTRAP Mass Spectrometer
    Yusuf Hannun; Fiscal Year: 2008
    ..Strong institutional commitment ensures long term operation and maintenance of the requested instrument and overall facility. [unreadable] [unreadable] [unreadable]..
  14. MODULATION OF CERAMIDE INDUCED APOPTOSIS IN VIVO
    Richard Kolesnick; Fiscal Year: 2009
    ..If results indicate that overexpressing ASMase effectively radiosensitizes tumor microvasculature, applicability to human tumor radiotherapy will be examined directly using human versions of lentiviral asmase vectors. ..
  15. Role of EGFR in Viral Infected Lung Epithelial Cells
    Martha M Monick; Fiscal Year: 2010
    ..Completion of these studies will add to our understanding of mechanisms of RSV infection of airway epithelium and the role of targeted signaling pathways in the subsequent inflammation and life span of infected cells. ..
  16. Lipid Raft Microdomains in Neutrophil Function
    ROBERT GARY SITRIN; Fiscal Year: 2010
    ..Hopefully, targeting the function of lipid raft microdomains will engender new therapeutic strategies for enhancing antimicrobial defenses and suppressing the deleterious effects of acute inflammation. ..
  17. Sphingolipid signaling induced by LDL immune complexes
    Samar M Hammad; Fiscal Year: 2010
    ..abstract_text> ..
  18. INTERACTION OF ATHEROGENIC LIPOPROTEINS WITH MACROPHAGES
    IRA A TABAS; Fiscal Year: 2010
    ..abstract_text> ..
  19. Computational Approach to Ligand Discovery for LPA GPCR and PPAR
    Abby L Parrill; Fiscal Year: 2010
    ..This research can therefore lead to new treatments for cardiovascular disease and cancer. ..
  20. Targeting KSR to Treat Pancreatic Cancer
    Richard N Kolesnick; Fiscal Year: 2010
    ....
  21. Sphingolipids in Ethanol-Induced Neuronal Apoptosis
    Mariko Saito; Fiscal Year: 2010
    ..These studies will reveal the functions of sphingolipids in ethanol-induced apoptosis in the developing brain, and will offer bases for future therapeutic strategies for FASD. ..
  22. CDP-choline: Mechanisms in Cerebral Ischemia
    RAO ADIBHATLA; Fiscal Year: 2006
    ..Arachidonic acid activates neutral sphingomyelinase, resulting in membrane disintegration. PCCT activity was stimulated by exogenous CDP-choline. Aim 2 will be tested in gerbil transient forebrain ischemia. ..
  23. Mechanisms of Cox2 Induced Tumorigenesis
    Timothy Hla; Fiscal Year: 2006
    ..Finally, we will employ a mass-spectrometry based state-of-the-art proteomic technology to identify novel polypeptides regulated by Cox-2 overexpression in the mammary gland, with a focus on mediators of apoptosis and angiogenesis. ..
  24. EDG-1 SIGNALING IN ANGIOGENESIS
    Timothy Hla; Fiscal Year: 2001
    ..The objective of this proposal is to define the signaling pathways involved in this morphogenetic differentiation, as well as definition of the phenotype of the edg-1-induced differentiated state. ..
  25. BLNK PROTEINS IN B CELL RECEPTOR FUNCTION
    Andrew Chan; Fiscal Year: 2002
    ....
  26. Conference--Neuronal Ceroid Lipofuscinosis
    Glyn Dawson; Fiscal Year: 2003
    ..abstract_text> ..
  27. CELLULAR AND MOLECULAR RESPONSES IN LUNG DISEASE
    Guy Zimmerman; Fiscal Year: 2003
    ..abstract_text> ..
  28. The Urokinase-CD87 System in Macrophage Activation
    Robert Sitrin; Fiscal Year: 2004
    ....
  29. FORM CELL APO (A)/LP(A) RECEPTOR--CLONING AND FUNCTION
    Ira Tabas; Fiscal Year: 2002
    ..The studies in this proposal will lead to the molecular identification of a novel cholesterol-induced receptor on foam cells and should provide important insight into the role of foam cell-apo(a)/Lp(a) interactions in atherogenesis. ..
  30. Graduate Medical Education in Genetics
    Margaret McGovern; Fiscal Year: 2004
    ..abstract_text> ..
  31. Keystone Symposium on Stroke, March 9-14, 2002
    Chung Hsu; Fiscal Year: 2002
    ..This conference, focusing on fundamental basic science on stroke, will be a much needed vehicle to advance stroke research. ..
  32. Sphingolipid modulators of vascular growth & homeostasis
    Timothy Hla; Fiscal Year: 2005
    ..These efforts will critically assess the central hypothesis that SKIEDG signaling system is a major regulator of angiogenesis. ..
  33. BASIS FOR ALCOHOL AND COCAINE STROKES--ROLE OF MG2+
    Burton Altura; Fiscal Year: 2004
    ..An understanding of how ethanol and cocaine induce strokes may ultimately suggest new targets for pharmacologic manipulation, and thus, improving the clinical outcome after "binge- drinking" or cocaine intoxication. ..
  34. LC/Q Mass Spectrometry for Lipid Analysis
    Yusuf Hannun; Fiscal Year: 2002
    ..4. Foster and further develop ongoing interdisciplinary research Among the various users. ..
  35. Conference on Cellular Biology of Atherosclerosis
    Ira Tabas; Fiscal Year: 2005
    ....
  36. Tenth International Congress on Ceroid Lipofuscinoses
    Glyn Dawson; Fiscal Year: 2005
    ....
  37. Macrophage Death in Plaque Vulnerability
    Ira Tabas; Fiscal Year: 2005
    ..New insights in this area may suggest new therapeutic strategies to combat cardiovascular disease. ..
  38. INFLAMMATORY APOPTOSIS AFTER SPINAL CORD INJURY
    Chung Hsu; Fiscal Year: 2001
    ..The ultimate goal of this project is to enhance functional recovery after SCI through a reduction in ODC death. ..
  39. SPHINGOMYELIN TURNOVER AND CELLULAR REGULATION
    Yusuf Hannun; Fiscal Year: 2006
    ..These pathways are of direct significance to the biology of stress responses and specifically to cancer therapeutics. ..
  40. REGULATION OF SPERM EXOCYTOSIS
    Nicholas Cross; Fiscal Year: 2002
    ..The cholesterol content of freshly ejaculated and oviductal bovine sperm will be compared to see if sperm lose cholesterol in the female tract. ..
  41. Targeted enzyme delivery systems for treatment of orphan niemann-pick disease
    SILVIA MURO GALINDO; Fiscal Year: 2007
    ..The clinical benefits of this strategy may be extended to other LSDs. [unreadable] [unreadable] [unreadable] [unreadable]..
  42. EFFECT OF DIETARY LIPIDS ON THE FUNCTION OF CHYLOMICRONS
    Byung Hong Chung; Fiscal Year: 2002
    ..abstract_text> ..
  43. Epigenetic toxicity of polycyclic aromatic hydrocarbons
    Brad Upham; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  44. Cellular Signaling Mechanisms in Macrophage Activation.
    Joseph Cuschieri; Fiscal Year: 2007
    ..Through an enhanced understanding of these mechanisms it is our goal that potential therapeutic targets may be discovered to regulate the inflammatory response following trauma/hemorrhage and ischemia/reperfusion. ..
  45. CYTOSKELETAL REGULATION OF ENDOTHELIAL CELL APOPTOSIS
    Irina Petrache; Fiscal Year: 2004
    ..abstract_text> ..
  46. Ceramide in angiogenic integrin signaling
    Anat Erdreich Epstein; Fiscal Year: 2006
    ....