amino acid chloromethyl ketones

Summary

Summary: Inhibitors of SERINE ENDOPEPTIDASES and sulfhydryl group-containing enzymes. They act as alkylating agents and are known to interfere in the translation process.

Top Publications

  1. pmc Cytochrome c maintains mitochondrial transmembrane potential and ATP generation after outer mitochondrial membrane permeabilization during the apoptotic process
    N J Waterhouse
    Division of Cellular Immunology, La Jolla Institute for Allergy and Immunology, San Diego, California 92121, USA
    J Cell Biol 153:319-28. 2001
  2. ncbi Q-VD-OPh, a broad spectrum caspase inhibitor with potent antiapoptotic properties
    T M Caserta
    Department of Physiology and Biophysics, Wright State University School of Medicine, Dayton, Ohio 45435, USA
    Apoptosis 8:345-52. 2003
  3. ncbi Nanosecond, high-intensity pulsed electric fields induce apoptosis in human cells
    Stephen J Beebe
    Center for Pediatric Research, 855 W Brambleton Ave, Norfolk, VA 23510, USA
    FASEB J 17:1493-5. 2003
  4. ncbi Dual antiglioma action of metformin: cell cycle arrest and mitochondria-dependent apoptosis
    A Isakovic
    Institute of Biochemistry, School of Medicine, University of Belgrade, Belgrade, Serbia
    Cell Mol Life Sci 64:1290-302. 2007
  5. ncbi Inhibition of human caspases by peptide-based and macromolecular inhibitors
    M Garcia-Calvo
    Department of Enzymology, Merck Research Laboratories, Rahway, New Jersey 07065, USA
    J Biol Chem 273:32608-13. 1998
  6. ncbi zVAD-fmk upregulates caspase-9 cleavage and activity in etoposide-induced cell death of mouse embryonic fibroblasts
    Aida Rodriguez-Enfedaque
    Universite de Versailles Saint Quentin en Yvelines, Ecole Pratique des Hautes Etudes, Versailles, France
    Biochim Biophys Acta 1823:1343-52. 2012
  7. ncbi Caspase inhibitor facilitates recovery of hearing by protecting the cochlear lateral wall from acute cochlear mitochondrial dysfunction
    Kunio Mizutari
    Laboratory of Auditory Disorders, National Institute of Sensory Organs, National Tokyo Medical Center, Tokyo, Japan
    J Neurosci Res 86:215-22. 2008
  8. ncbi The optimal activity of a pseudozymogen form of recombinant matriptase under the mildly acidic pH and low ionic strength conditions
    Kuniyo Inouye
    Laboratory of Enzyme Chemistry, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Sakyo ku, Kyoto City 606 8502, Japan
    J Biochem 147:485-92. 2010
  9. ncbi Caspase-3 is required for alpha-fodrin cleavage but dispensable for cleavage of other death substrates in apoptosis
    R U Jänicke
    Institute of Molecular and Cell Biology, The National University of Singapore, 30 Medical Dr, Singapore 117609, Republic of Singapore
    J Biol Chem 273:15540-5. 1998
  10. ncbi G-protein-coupled OX1 orexin/hcrtr-1 hypocretin receptors induce caspase-dependent and -independent cell death through p38 mitogen-/stress-activated protein kinase
    Sylwia Ammoun
    Department of Neuroscience, Unit of Physiology, Uppsala University, Sweden
    J Biol Chem 281:834-42. 2006

Detail Information

Publications201 found, 100 shown here

  1. pmc Cytochrome c maintains mitochondrial transmembrane potential and ATP generation after outer mitochondrial membrane permeabilization during the apoptotic process
    N J Waterhouse
    Division of Cellular Immunology, La Jolla Institute for Allergy and Immunology, San Diego, California 92121, USA
    J Cell Biol 153:319-28. 2001
    ....
  2. ncbi Q-VD-OPh, a broad spectrum caspase inhibitor with potent antiapoptotic properties
    T M Caserta
    Department of Physiology and Biophysics, Wright State University School of Medicine, Dayton, Ohio 45435, USA
    Apoptosis 8:345-52. 2003
    ..Our data indicate that the specificity, effectiveness, and reduced toxicity of caspase inhibitors can be significantly enhanced using carboxyterminal o-phenoxy groups and may have important uses in vivo...
  3. ncbi Nanosecond, high-intensity pulsed electric fields induce apoptosis in human cells
    Stephen J Beebe
    Center for Pediatric Research, 855 W Brambleton Ave, Norfolk, VA 23510, USA
    FASEB J 17:1493-5. 2003
    ..NsPEF technology provides a unique, high-power, energy-independent tool to recruit plasma membrane and/or intracellular signaling mechanisms that can delete aberrant cells by apoptosis...
  4. ncbi Dual antiglioma action of metformin: cell cycle arrest and mitochondria-dependent apoptosis
    A Isakovic
    Institute of Biochemistry, School of Medicine, University of Belgrade, Belgrade, Serbia
    Cell Mol Life Sci 64:1290-302. 2007
    ..Similar effects were observed in the human glioma cell line U251, while rat primary astrocytes were completely resistant to the antiproliferative and proapoptotic action of metformin...
  5. ncbi Inhibition of human caspases by peptide-based and macromolecular inhibitors
    M Garcia-Calvo
    Department of Enzymology, Merck Research Laboratories, Rahway, New Jersey 07065, USA
    J Biol Chem 273:32608-13. 1998
    ....
  6. ncbi zVAD-fmk upregulates caspase-9 cleavage and activity in etoposide-induced cell death of mouse embryonic fibroblasts
    Aida Rodriguez-Enfedaque
    Universite de Versailles Saint Quentin en Yvelines, Ecole Pratique des Hautes Etudes, Versailles, France
    Biochim Biophys Acta 1823:1343-52. 2012
    ..Altogether, our data suggest that caspase-9 activity is up-regulated by zVAD-fmk and is involved in an amplification loop of etoposide-induced cell death at the mitochondrial level in MEFs...
  7. ncbi Caspase inhibitor facilitates recovery of hearing by protecting the cochlear lateral wall from acute cochlear mitochondrial dysfunction
    Kunio Mizutari
    Laboratory of Auditory Disorders, National Institute of Sensory Organs, National Tokyo Medical Center, Tokyo, Japan
    J Neurosci Res 86:215-22. 2008
    ..Moreover, the results of the present study suggest that systemic administration of a caspase inhibitor may be an effective therapy for sensorineural hearing loss caused by acute energy failure such as that observed in cochlear ischemia...
  8. ncbi The optimal activity of a pseudozymogen form of recombinant matriptase under the mildly acidic pH and low ionic strength conditions
    Kuniyo Inouye
    Laboratory of Enzyme Chemistry, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Sakyo ku, Kyoto City 606 8502, Japan
    J Biochem 147:485-92. 2010
    ..These findings suggest that the in vivo activation of matriptase zymogen occurs via a mechanism involving the zymogen activity...
  9. ncbi Caspase-3 is required for alpha-fodrin cleavage but dispensable for cleavage of other death substrates in apoptosis
    R U Jänicke
    Institute of Molecular and Cell Biology, The National University of Singapore, 30 Medical Dr, Singapore 117609, Republic of Singapore
    J Biol Chem 273:15540-5. 1998
    ....
  10. ncbi G-protein-coupled OX1 orexin/hcrtr-1 hypocretin receptors induce caspase-dependent and -independent cell death through p38 mitogen-/stress-activated protein kinase
    Sylwia Ammoun
    Department of Neuroscience, Unit of Physiology, Uppsala University, Sweden
    J Biol Chem 281:834-42. 2006
    ....
  11. ncbi A giant protease with potential to substitute for some functions of the proteasome
    E Geier
    Max Planck Institute of Immunobiology, Stubeweg 51, D 79108 Freiburg, Germany
    Science 283:978-81. 1999
    ..In addition, TPPII may be able to substitute for some metabolic functions of the proteasome...
  12. ncbi Caspase 6 activity initiates caspase 3 activation in cerebellar granule cell apoptosis
    T E Allsopp
    Fujisawa Institute for Neuroscience in Edinburgh, The Department of Neuroscience, The University of Edinburgh, Edinburgh EH8 9JZ, UK
    Cell Death Differ 7:984-93. 2000
    ..This would indicate that caspase 6 is a significant inducer of the early caspase 3 activity in apoptotic CGCs...
  13. pmc Caspase activation is required for terminal erythroid differentiation
    Y Zermati
    Centre National de la Recherche Scientifique Unité Mixte de Recherche 8603, Universite Rene Descartes, Paris V, France
    J Exp Med 193:247-54. 2001
    ..These observations indicate a new function for caspases as key proteases in the process of erythroid differentiation...
  14. ncbi Regulation of an ATG7-beclin 1 program of autophagic cell death by caspase-8
    Li Yu
    Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Science 304:1500-2. 2004
    ..Clinical therapies involving caspase inhibitors may arrest apoptosis but also have the unanticipated effect of promoting autophagic cell death...
  15. ncbi Caspases induce cytochrome c release from mitochondria by activating cytosolic factors
    E Bossy-Wetzel
    Division of Cellular Immunology, La Jolla Institute for Allergy and Immunology, San Diego, California 92121, USA
    J Biol Chem 274:17484-90. 1999
    ..Our data suggest that cytochrome c release, initiated by the action of caspases on a cytosolic substrates, may act to amplify a caspase cascade during apoptosis...
  16. ncbi Differential effects of caspase inhibitors on endotoxin-induced myocardial dysfunction and heart apoptosis
    H Fauvel
    , Lille Cedex, 59045, France
    Am J Physiol Heart Circ Physiol 280:H1608-14. 2001
    ..Caspase inhibition strategy may represent a therapeutic approach to endotoxin-induced myocardial dysfunction...
  17. ncbi The augmentation of TNFalpha-induced cell death in murine L929 fibrosarcoma by the pan-caspase inhibitor Z-VAD-fmk through pre-mitochondrial and MAPK-dependent pathways
    Jian Huang
    China Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang, PR China
    Acta Med Okayama 59:253-60. 2005
    ....
  18. pmc Inhibition of caspase 3 abrogates lipopolysaccharide-induced nitric oxide production by preventing activation of NF-kappaB and c-Jun NH2-terminal kinase/stress-activated protein kinase in RAW 264.7 murine macrophage cells
    D Chakravortty
    Department of Microbiology and Immunology and Division of Bacterial Toxin, Research Center for Infectious Disease, Aichi Medical University School of Medicine, Nagakute, Aichi 480-1195, Japan
    Infect Immun 69:1315-21. 2001
    ..The caspase family, especially caspase 3, is likely to play an important role in the signal transduction for iNOS-mediated NO production in LPS-stimulated mouse macrophages...
  19. pmc Ligand binding to anion-binding exosites regulates conformational properties of thrombin
    Marina V Malovichko
    Chemistry Department, University of Louisville, Louisville, Kentucky 40292, USA
    J Biol Chem 288:8667-78. 2013
    ..The results obtained support the proposal that thrombin is a highly dynamic protein. The transmission of ligand-specific local and long range conformational events is proposed to help regulate this multifunctional enzyme...
  20. ncbi Long-lasting antinociceptive effect of DAMGO chloromethyl ketone in rats
    G Szabo
    Department of Pathophysiology, Albert Szent Gyorgyi Medical University, Szeged, Hungary
    Peptides 20:1321-6. 1999
    ..Central administration of DAMCK also elicited time- and concentration-dependent, profound, opioid receptor mediated, apparently irreversible antinociception...
  21. ncbi ICE-protease inhibitors block murine liver injury and apoptosis caused by CD95 or by TNF-alpha
    G Künstle
    Department of Biochemical Pharmacology, Faculty of Biology, University of Konstanz, Germany
    Immunol Lett 55:5-10. 1997
    ..These findings show in vitro and in vivo in mammals that CD95 and the TNF-alpha receptor share a distal proteolytic apoptosis signal...
  22. ncbi The coordinate release of cytochrome c during apoptosis is rapid, complete and kinetically invariant
    J C Goldstein
    Division of Cellular Immunology, La Jolla Institute for Allergy and Immunology, 10355 Science Center Drive, San Diego, California 92121, USA
    Nat Cell Biol 2:156-62. 2000
    ..Further, we find that the electron-transport chain can maintain the mitochondrial transmembrane potential even after cytochrome c has been released...
  23. ncbi Requirement for caspase-8 in NF-kappaB activation by antigen receptor
    Helen Su
    Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Science 307:1465-8. 2005
    ..These findings thus explain the paradoxical association of defective apoptosis and combined immunodeficiency in human CED...
  24. ncbi z-VAD-fmk inhibits peptide:N-glycanase and may result in ER stress
    S Misaghi
    Cell Death Differ 13:163-5. 2006
  25. ncbi Mitochondria are selectively eliminated from eukaryotic cells after blockade of caspases during apoptosis
    L Xue
    Department of Biochemistry, University of Cambridge, Cambridge CB2 1QW, United Kingdom
    Curr Biol 11:361-5. 2001
    ..Prevention of mitochondrial loss may be crucial for the long-term regeneration of tissues emerging from an apoptotic episode in which death was prevented by caspase blockade...
  26. ncbi Docetaxel-induced apoptosis in melanoma cells is dependent on activation of caspase-2
    Nizar M Mhaidat
    Immunology and Oncology Unit, Royal Newcastle Hospital, Room 443, David Maddison Clinical Sciences Building, Corner King and Watt Streets, Newcastle, NSW 2300, Australia
    Mol Cancer Ther 6:752-61. 2007
    ..These results suggest that docetaxel induces apoptosis in melanoma cells by pathways that are dependent on activation of caspase-2, which initiates mitochondrial dependent apoptosis by direct or indirect activation of Bax...
  27. ncbi Modulation of tumor necrosis factor apoptosis-inducing ligand- induced NF-kappa B activation by inhibition of apical caspases
    N Harper
    MRC Toxicology Unit, Hodgkin Building, University of Leicester, P. O. Box 138, Lancaster Road, Leicester LE1 9HN, United Kingdom
    J Biol Chem 276:34743-52. 2001
    ..Thus, in some contexts, modulation of NF-kappaB activation possibly at the level of apical caspase activation at the DISC may be a key determinant of sensitivity to TRAIL-induced apoptosis...
  28. ncbi The role of caspases in cryoinjury: caspase inhibition strongly improves the recovery of cryopreserved hematopoietic and other cells
    Christopher Stroh
    Institute of Experimental Dermatology, University of Munster, D 48149 Munster, Germany
    FASEB J 16:1651-3. 2002
    ..The addition of caspase inhibitors may be an important tool for the cryopreservation of living cells and advantageous in cell transplantation, tissue engineering, and other genetic technologies...
  29. ncbi Caspase activation contributes to endotoxin-induced diaphragm weakness
    Gerald S Supinski
    Department of Medicine, 1120 15th St, Rm BBR 5513, Medical College of Georgia, Augusta, GA 30912 3135, USA
    J Appl Physiol (1985) 100:1770-7. 2006
    ..001). Caspase inhibitors also prevented spectrin degradation. In conclusion, endotoxin administration elicits significant diaphragm caspase 3 activation and caspase-mediated diaphragmatic weakness...
  30. ncbi The caspase selective inhibitor EP1013 augments human islet graft function and longevity in marginal mass islet transplantation in mice
    Juliet A Emamaullee
    Department of Surgery, University of Alberta, Edmonton, Alberta, Canada
    Diabetes 57:1556-66. 2008
    ..EP1013 (N-benzyloxycabonyl-Val Asp-fluoromethyl ketone [zVD-FMK]), is a broad-spectrum caspase selective inhibitor with no observed toxicity in rodents...
  31. pmc Sex differences in caspase activation after stroke
    Fudong Liu
    Department of Neurology and Neuroscience, University of Connecticut Health Center, Farmington, Connecticut, USA
    Stroke 40:1842-8. 2009
    ..The aim of this study is to examine whether sex differences exist in caspase activation in adult mice after stroke and to determine if interference with stroke-induced caspase activation preferentially protects females...
  32. ncbi Efficient nuclear targeting of granzyme B and the nuclear consequences of apoptosis induced by granzyme B and perforin are caspase-dependent, but cell death is caspase-independent
    J A Trapani
    The John Connell Laboratory, The Austin Research Institute, Studley Road, Heidelberg 3084, Australia
    J Biol Chem 273:27934-8. 1998
    ..We conclude that cell death in response to perforin and granzyme B does not require caspase activation and still proceeds efficiently through non-nuclear pathways when nuclear substrate cleavage is inhibited...
  33. ncbi Alternative cleavage of Alzheimer-associated presenilins during apoptosis by a caspase-3 family protease
    T W Kim
    Genetics and Aging Unit, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA
    Science 277:373-6. 1997
    ....
  34. ncbi Apoptosis by pan-caspase inhibitors in lipopolysaccharide-activated macrophages
    S O Kim
    Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA
    Am J Physiol Lung Cell Mol Physiol 281:L1095-105. 2001
    ....
  35. ncbi Two Arabidopsis metacaspases AtMCP1b and AtMCP2b are arginine/lysine-specific cysteine proteases and activate apoptosis-like cell death in yeast
    Naohide Watanabe
    Biotechnology Center for Agriculture and the Environment, Rutgers, The State University of New Jersey, New Brunswick, New Jersey 08901 8520, USA
    J Biol Chem 280:14691-9. 2005
    ..Metacaspases from higher plants may serve similar functions...
  36. ncbi Anti-apoptotic factor z-Val-Ala-Asp-fluoromethylketone promotes the survival of cochlear hair cells in a mouse model for human deafness
    O Atar
    Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
    Neuroscience 168:851-7. 2010
    ..These results help towards providing a comprehensive understanding of the molecular mechanisms of hair cell death, which might lead to the development of new therapeutic anti-apoptotic agents to alleviate hereditary hearing loss (HL)...
  37. pmc Expansion of cord blood CD34 cells in presence of zVADfmk and zLLYfmk improved their in vitro functionality and in vivo engraftment in NOD/SCID mouse
    V M Sangeetha
    Stem Cell Biology Laboratory, National Centre for Cell Science, Pune, Maharashtra, India
    PLoS ONE 5:e12221. 2010
    ..The present study was undertaken to assess whether pharmacological inhibition of apoptosis could improve the outcome of expansion...
  38. pmc The refined 1.9 A crystal structure of human alpha-thrombin: interaction with D-Phe-Pro-Arg chloromethylketone and significance of the Tyr-Pro-Pro-Trp insertion segment
    W Bode
    Max Planck Institut fur Biochemie, Martinsried, FRG
    EMBO J 8:3467-75. 1989
    ..The narrow active site cleft, with a more polar base and hydrophobic rims, extends towards the arginine-rich surface of loop Lys70-Glu80 that probably represents part of the anionic binding region for hirudin and fibrinogen...
  39. pmc Role of Bcl-2 family members in caspase-independent apoptosis during Chlamydia infection
    Jean Luc Perfettini
    Unité de Biologie Moléculaire du Gène, INSERM U 277, Universite Paris 7, France
    Infect Immun 70:55-61. 2002
    ....
  40. ncbi The contraction phase of virus-specific CD8+ T cells is unaffected by a pan-caspase inhibitor
    Alexander K Nussbaum
    Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037, USA
    J Immunol 173:6611-8. 2004
    ..We conclude that the contraction phase of the virus-specific T cell response is unlikely to require caspase-dependent PCD. We propose that contraction can be mediated by an alternative, caspase-independent pathway(s)...
  41. ncbi Caspase inhibition causes hyperacute tumor necrosis factor-induced shock via oxidative stress and phospholipase A2
    Anje Cauwels
    Molecular Pathophysiology and Experimental Therapy Unit, Department for Molecular Biomedical Research, Ghent University and Flanders Interuniversity Institute for Biotechnology, Ghent, Belgium
    Nat Immunol 4:387-93. 2003
    ..In addition, survival of TNF toxicity seemed to require a caspase-dependent protective feedback on excessive reactive oxygen species (ROS) formation and phospholipase A2 activation...
  42. ncbi Involvement of lysosomal cathepsins in the cleavage of DNA topoisomerase I during necrotic cell death
    Fabio J Pacheco
    Loma Linda University School of Medicine, Loma Linda, California 92350, USA
    Arthritis Rheum 52:2133-45. 2005
    ..These autoantibodies recognize topo I and fragments of this autoantigen generated during apoptosis and necrosis. We undertook this study to determine whether lysosomal cathepsins are involved in topo I fragmentation during necrosis...
  43. ncbi Cathepsin-dependent apoptosis triggered by supraoptimal activation of T lymphocytes: a possible mechanism of high dose tolerance
    Marie Cecile Michallet
    Laboratoire d Immunopharmacologie, Institut National de la Santé et de la Recherche Médicale Unité 503, Centre d Etudes et de Recherche en Virologie et Immunologie, Lyon, France
    J Immunol 172:5405-14. 2004
    ..These results demonstrate a role for cathepsins in supraoptimal activation-induced apoptosis in vitro and suggest their possible participation in high dose tolerance in vivo...
  44. ncbi Caspase inhibition blocks human T cell proliferation by suppressing appropriate regulation of IL-2, CD25, and cell cycle-associated proteins
    Markus Falk
    Institut fur Immunologie, Universitätsklinikum Schleswig Holstein Campus Kiel, Germany
    J Immunol 173:5077-85. 2004
    ..Finally, we provide evidence that caspase inhibition suppresses the activation of purified monocytes by bacterial Ags...
  45. ncbi Inhibition of papain-like cysteine proteases and legumain by caspase-specific inhibitors: when reaction mechanism is more important than specificity
    J Rozman-Pungercar
    Department of Biochemistry and Molecular Biology, J Stefan Institute, Jamova 39, SI 1000 Ljubljana, Slovenia
    Cell Death Differ 10:881-8. 2003
    ..These results suggest that data based on the use of these inhibitors should be taken with caution and that other proteases may be implicated in the processes previously ascribed solely to caspases...
  46. ncbi Endoplasmic reticulum localized Bcl-2 prevents apoptosis when redistribution of cytochrome c is a late event
    M G Annis
    Department of Biochemistry, McMaster University, Hamilton, L8N 3Z5, Canada
    Oncogene 20:1939-52. 2001
    ..Therefore, Bcl-2 functions in spatially distinct pathways of apoptosis distinguished by the order of cytochrome c release and loss of Deltapsi(m)...
  47. ncbi Role of caspases in CD95L- and TRAIL-induced non-apoptotic signalling in pancreatic tumour cells
    Daniela Siegmund
    Department of Molecular Internal Medicine, Medical Clinic and Polyclinic II, University of Wuerzburg, and Division of Molecular Oncology, Clinic for General Surgery and Thoracic Surgery, University Hospital Schleswig Holstein, Kiel, Germany
    Cell Signal 19:1172-84. 2007
    ..Consequently, an NFkappaB and ERK stimulating, caspase-dependent factor must operate downstream of the DISC in Colo357-BclxL cells...
  48. pmc Caspase-mediated loss of mitochondrial function and generation of reactive oxygen species during apoptosis
    Jean Ehrland Ricci
    Division of Cellular Immunology, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121, USA
    J Cell Biol 160:65-75. 2003
    ....
  49. ncbi Functional caspase-1 is required for Langerhans cell migration and optimal contact sensitization in mice
    C Antonopoulos
    Center for Dermatology, Department of Medicine, University College London, London, United Kingdom
    J Immunol 166:3672-7. 2001
    ..Taken together, these data indicate that caspase-1 may play a central role in the regulation of LC migration and suggest that the activity of this enzyme is amenable to control by specific inhibitors both in vivo and in vitro...
  50. ncbi Secondary necrosis is a source of proteolytically modified forms of specific intracellular autoantigens: implications for systemic autoimmunity
    X Wu
    Loma Linda University School of Medicine, California, USA
    Arthritis Rheum 44:2642-52. 2001
    ....
  51. ncbi Selective inhibition of dipeptidyl peptidase I, not caspases, prevents the partial processing of procaspase-3 in CD3-activated human CD8(+) T lymphocytes
    Nicolas Bidere
    Laboratoire de Greffes d Epithéliums et Régulation de l Activation Lymphocytaire, Unité INSERM 542, Hopital Paul Brousse, 94807 Villejuif, France
    J Biol Chem 277:32339-47. 2002
    ..Small amounts of GrB were indeed exported from cytolytic granules to the cytosol of a significant fraction of GrB-positive cells...
  52. ncbi Inhibition of caspase or FADD function blocks proliferation but not MAP kinase-activation and interleukin-2-production during primary stimulation of T cells
    Astrid Mack
    Institute of Medical Microbiology, Immunology and Hygiene, Technical University Munich, Munich, Germany
    Eur J Immunol 32:1986-92. 2002
    ..These data show a distinct role of caspases during primaryT cell activation and provide evidence for a FADD-caspase-pathway not only in the induction of apoptosis but also of T cell proliferation...
  53. ncbi Rescue of defective branching nephrogenesis in renal-coloboma syndrome by the caspase inhibitor, Z-VAD-fmk
    Patsy Clark
    Department of Human Genetics, McGill University, Montreal, Quebec, Canada
    J Am Soc Nephrol 15:299-305. 2004
    ..Furthermore, it suggests that caspase inhibitors can rescue the branching defect caused by PAX2 mutations...
  54. ncbi Caspase-dependent cell death mediates the early phase of aortic hypertrophy regression in losartan-treated spontaneously hypertensive rats
    Eve Lyne Marchand
    Department of Pharmacology, University of Montreal Hospital Research Center, 3840 St Urbain St, Rm 7 132B, Montreal, Quebec H2W 1T8, Canada
    Circ Res 92:777-84. 2003
    ..Together, these data suggest that caspase-dependent SMC death mediates the early phase of vascular remodeling in response to AT1 receptor blockade in this model of hypertension...
  55. ncbi Allosteric changes in solvent accessibility observed in thrombin upon active site occupation
    Carrie Hughes Croy
    Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093 0378, USA
    Biochemistry 43:5246-55. 2004
    ..These results indicate two pathways of allosteric change that connect the active site to the distal anion binding exosite 1...
  56. ncbi Caspase inhibitor therapy enhances marginal mass islet graft survival and preserves long-term function in islet transplantation
    Juliet A Emamaullee
    Department of Surgery, University of Alberta, Edmonton, Alberta, Canada
    Diabetes 56:1289-98. 2007
    ..Our data suggest that caspase inhibitor therapy will reduce the islet mass required in clinical islet transplantation, perhaps to a level that would routinely allow for insulin independence after single-donor infusion...
  57. ncbi Differential localization and regulation of death and decoy receptors for TNF-related apoptosis-inducing ligand (TRAIL) in human melanoma cells
    X D Zhang
    Department of Oncology and Immunology, John Hunter Hospital, Newcastle, Australia
    J Immunol 164:3961-70. 2000
    ....
  58. ncbi Caspase inhibitor Z-VAD-FMK enhances the freeze-thaw survival rate of human embryonic stem cells
    Boon Chin Heng
    Stem Cell Laboratory, Faculty of Dentistry, National University of Singapore, Singapore, Singapore
    Biosci Rep 27:257-64. 2007
    ..The results demonstrated that exposure to Z-VAD-FMK did not significantly enhance the spontaneous differentiation of hESC within post-thaw culture...
  59. ncbi Elevated vulnerability to oxidative stress-induced cell death and activation of caspase-3 by the Swedish amyloid precursor protein mutation
    A Eckert
    Department of Pharmacology, Biocenter, University of Frankfurt, Frankfurt, Germany
    J Neurosci Res 64:183-92. 2001
    ....
  60. ncbi Calpain activation is upstream of caspases in radiation-induced apoptosis
    N J Waterhouse
    Queensland Cancer Fund Research Unit, Queensland Institute of Medical Research, Royal Brisbane Hospital, Herston, Australia
    Cell Death Differ 5:1051-61. 1998
    ..These results support a role for calpain in the early phases of the radiation-induced apoptosis pathway, upstream of the caspases...
  61. pmc Blocking cytochrome c activity within intact neurons inhibits apoptosis
    S J Neame
    Eisai London Research Laboratories, Bernard Katz Building, University College London, London WC1E 6BT, United Kingdom
    J Cell Biol 142:1583-93. 1998
    ..These data suggest that cytochrome c is an intrinsic but not limiting component of the neuronal apoptotic pathway...
  62. pmc Caspase-mediated cleavage of the stacking protein GRASP65 is required for Golgi fragmentation during apoptosis
    Jon D Lane
    School of Biological Sciences, University of Manchester, Manchester M13 9PT, United Kingdom
    J Cell Biol 156:495-509. 2002
    ..Our results suggest that GRASP65 is an important structural component required for maintenance of Golgi apparatus integrity...
  63. ncbi Activation of caspase-3 in renal cell carcinoma cells by anthracyclines or 5-fluorouracil
    X X Wu
    Department of Urology, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan
    Int J Oncol 19:19-24. 2001
    ..These findings provide a mechanistic explanation for anthracyclines and 5-FU induced-apoptosis...
  64. pmc Caspase I-related protease inhibition retards the execution of okadaic acid- and camptothecin-induced apoptosis and PAI-2 cleavage, but not commitment to cell death in HL-60 cells
    P H Jensen
    Department of Medical Biochemistry, Aarhus University, Aarhus C, Denmark
    Br J Cancer 79:1685-91. 1999
    ..The results suggest that caspase I selective protease inhibition could antagonize parameters coupled to the execution phase of okadaic acid- and camptothecin-induced apoptosis, but not the commitment to cell death...
  65. ncbi BID: a novel BH3 domain-only death agonist
    K Wang
    Department of Medicine and Pathology, Howard Hughes Medical Institute, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Genes Dev 10:2859-69. 1996
    ..This BH3-only molecule supports BH3 as a death domain and favors a model in which BID represents a death ligand for the membrane-bound receptor BAX...
  66. ncbi Distinct cleavage products of nuclear proteins in apoptosis and necrosis revealed by autoantibody probes
    C A Casiano
    WM Keck Autoimmune Disease Center, Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USA
    Cell Death Differ 5:183-90. 1998
    ....
  67. ncbi An atypical caspase-independent death pathway for an immunogenic cancer cell line
    Nicolas Larmonier
    INSERM U517, IFR 100, Faculty of Medicine and Pharmacy, 7 Boulevard Jeanne d Arc, 21079 Dijon, France
    Oncogene 21:6091-100. 2002
    ..This unusual mode of cell death that associates necrotic and apoptotic features could provide optimal conditions for triggering a specific immune response...
  68. ncbi Phosphatidylserine efflux and intercellular fusion in a BeWo model of human villous cytotrophoblast
    M Das
    Department of Obstetrics and Gynecology, MetroHealth Medical Center, Case Western Reserve University School of Medicine, Cleveland, OH, USA
    Placenta 25:396-407. 2004
    ..There was no indication of apoptosis associated with differentiation. Thus, PS efflux and intercellular fusion occurred through a vanadate-sensitive mechanism that was independent of apoptosis...
  69. ncbi Expression of dengue ApoptoM sequence results in disruption of mitochondrial potential and caspase activation
    Adeline Catteau
    Unité des Interactions Moléculaires Flavivirus Hôtes, Institut Pasteur, 25, rue du Dr Roux, 75015 Paris, France
    Biochimie 85:789-93. 2003
    ..However, there was no role for caspase-9 in ApoptoM-mediated cell death. Our data suggest that a particular mitochondrion-dependent apoptotic pathway may be involved in induction of apoptosis by ApoptoM...
  70. ncbi Lethal toxin from Clostridium sordellii induces apoptotic cell death by disruption of mitochondrial homeostasis in HL-60 cells
    Patrice Petit
    Institut Cochin, INSERM U567, Department of Developmental Genetic and Molecular PathologyICGM, 24 rue du Faubourg Saint Jacques, 75014 Paris, France
    Cell Microbiol 5:761-71. 2003
    ..Cell exposure to LT-IP82 leads to a co-localization of the toxin with a mitochondrial marker within 2 h. Therefore, we suggest that LT-IP82 could act at the mitochondrion level independently of its enzymatic effect on small GTPases...
  71. ncbi LIGHT sensitizes IFN-gamma-mediated apoptosis of HT-29 human carcinoma cells through both death receptor and mitochondria pathways
    Man Chao Zhang
    Division of Hematology Oncology, Department of Internal Medicine, The University of Michigan, Ann Arbor, MI 48109 0934, USA
    Cell Res 14:117-24. 2004
    ..These results suggest that LIGHT-induced, IFNg-mediated apoptosis of HT-29 cells is caspase-dependent, and LIGHT signaling is mediated through both death receptor and mitochondria pathways...
  72. ncbi Blocking granule-mediated death by primary human NK cells requires both protection of mitochondria and inhibition of caspase activity
    K A Sedelies
    Cancer Cell Death Laboratory, Cancer Immunology Program, Peter MacCallum Cancer Centre, Locked Bag 1, A Beckett Street, Melbourne, Victoria 8006, Australia
    Cell Death Differ 15:708-17. 2008
    ....
  73. ncbi The histone deacetylase inhibitor suberic bishydroxamate regulates the expression of multiple apoptotic mediators and induces mitochondria-dependent apoptosis of melanoma cells
    Xu Dong Zhang
    Immunology and Oncology Unit, Royal Newcastle Hospital, Newcastle, New South Wales, Australia
    Mol Cancer Ther 3:425-35. 2004
    ..These results suggest that SBHA induces apoptosis by changing the balance between proapoptotic and antiapoptotic proteins in melanoma cells. The protein Bim may be a key initiator of apoptosis in cells treated with SBHA...
  74. ncbi Nonoxynol-9 induces apoptosis of endometrial explants by both caspase-dependent and -independent apoptotic pathways
    John K Jain
    Department of Obstetrics and Gynecology, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA
    Biol Reprod 73:382-8. 2005
    ..It appears that other factors besides caspases are also involved in the N-9-induced apoptosis...
  75. ncbi Caspase-dependent apoptosis induction by phenethyl isothiocyanate, a cruciferous vegetable-derived cancer chemopreventive agent, is mediated by Bak and Bax
    Dong Xiao
    Department of Pharmacology, University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA
    Clin Cancer Res 11:2670-9. 2005
    ....
  76. ncbi Functional dissociation of DeltaPsim and cytochrome c release defines the contribution of mitochondria upstream of caspase activation during granzyme B-induced apoptosis
    N J Waterhouse
    Cancer Cell Death, Peter MacCallum Cancer Centre, Locked Bag 1, A Beckett Street, Melbourne, Victoria 8006, Australia
    Cell Death Differ 13:607-18. 2006
    ..This functional dissociation of cytochrome c and SMAC release from loss of DeltaPsim demonstrates the essential contribution of Bid upstream of caspase activation during granzyme B-induced apoptosis...
  77. ncbi Capsaicin-induced apoptosis and reduced release of reactive oxygen species in MBT-2 murine bladder tumor cells
    Ji Seon Lee
    College of Pharmacy, Yeungnam University, Gyongsan 712 749, Korea
    Arch Pharm Res 27:1147-53. 2004
    ..These results further suggest that capsaicin may be a valuable intravesical chemotherapeutic agent for bladder cancers...
  78. ncbi Caspase-3 is required in the apoptotic disintegration of the nuclear matrix
    Katri Kivinen
    Department of Pathology, University of Turku, MediCity Research Laboratory, Tykistokatu 6 A, 4th Floor, FIN 20520 Turku, Finland
    Exp Cell Res 311:62-73. 2005
    ..These results show that caspase-3 is involved in the cleavage of NuMA and lamins either directly or by activating other proteases. This may be essential for disintegration of the nuclear structure during apoptosis...
  79. ncbi CD95 apoptosis resistance in certain cells can be overcome by noncanonical activation of caspase-8
    B C Barnhart
    The Ben May Institute for Cancer Research, University of Chicago, Chicago, IL 60637, USA
    Cell Death Differ 12:25-37. 2005
    ..Our data suggest that it is possible to overcome the CD95 apoptosis resistance of many tumor cells that do not efficiently form a DISC through noncanonical activation of the caspase-8 proenzyme...
  80. ncbi Contribution of reactive oxygen species and caspase-3 to apoptosis and attenuated ICAM-1 expression by paclitaxel-treated MDA-MB-435 breast carcinoma cells
    Helen Fawcett
    Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia B3H 1X5, Canada
    Int J Oncol 27:1717-26. 2005
    ....
  81. ncbi Protein kinase C delta is not activated by caspase-3 and its inhibition is sufficient to induce apoptosis in the colon cancer line, COLO 205
    Aurélia E Lewis
    Division of Medical Sciences, The Medical School, University of Birmingham, B15 2TT, UK
    Cell Signal 17:253-62. 2005
    ..We conclude that in colonocytes, inhibition of PKCdelta is sufficient to lead to caspase-3-independent apoptosis. Caspase-3 does not cleave PKCdelta to an active form, nor does caspase-3 inhibition block apoptosis...
  82. pmc Khat (Catha edulis)-induced apoptosis is inhibited by antagonists of caspase-1 and -8 in human leukaemia cells
    E A O Dimba
    Department of Odontology Oral Pathology and Forensic Odontology, Faculty of Dentistry and Centre for International Health, University of Bergen, Bergen, Norway
    Br J Cancer 91:1726-34. 2004
    ..It is concluded that khat induces a rather swift and sensitive cell death by apoptosis through mechanisms involving activation of caspase-1, -3 and -8...
  83. ncbi Tauroursodeoxycholic acid modulates p53-mediated apoptosis in Alzheimer's disease mutant neuroblastoma cells
    Rita M Ramalho
    Centro de Patogenese Molecular, Faculty of Pharmacy, University of Lisbon, Portugal
    J Neurochem 98:1610-8. 2006
    ..In conclusion, FAD mutations are associated with the activation of classical apoptotic pathways. TUDCA reduces p53-induced apoptosis and modulates expression of Bcl-2 family...
  84. ncbi Mitochondria-dependent apoptosis induced by nanoscale hydroxyapatite in human gastric cancer SGC-7901 cells
    Xiaojuan Chen
    Department of Gastroenterology, Zhongnan Hospital, Wuhan University, China
    Biol Pharm Bull 30:128-32. 2007
    ....
  85. ncbi Molecular mechanism of diclofenac-induced apoptosis of promyelocytic leukemia: dependency on reactive oxygen species, Akt, Bid, cytochrome and caspase pathway
    Akiko Inoue
    Department of Pediatrics, Osaka Medical College, Takatsuki 569 8686, Japan
    Free Radic Biol Med 37:1290-9. 2004
    ....
  86. ncbi When cells die II: a comprehensive evaluation of apoptosis and programmed cell death
    A Villunger
    Cell Death Differ 11:790-3. 2004
  87. ncbi Apoptosis in human oral squamous cell carcinomas is induced by 15-deoxy-delta 12,14-prostaglandin J2 but not by troglitazone
    K Fukuchi
    First Department of Oral and Maxillofacial Surgery, Osaka Dental University, Hirakata, Japan
    J Dent Res 82:802-6. 2003
    ..Our study demonstrates that treatment with 15-d-PGJ(2), but not troglitazone, induces apoptosis in human SCC cell lines, and 15-d-PGJ(2) appears to work through cytochrome c release and caspase activation...
  88. ncbi Interleukin-5 inhibits translocation of Bax to the mitochondria, cytochrome c release, and activation of caspases in human eosinophils
    G Dewson
    Institute for Lung Health, University of Leicester, Glenfield Hospital, Leicester, United Kingdom
    Blood 98:2239-47. 2001
    ..IL-5 inhibits spontaneous eosinophil apoptosis at a site upstream of Bax translocation...
  89. ncbi Mitochondrial dysfunction is an essential step for killing of non-small cell lung carcinomas resistant to conventional treatment
    Bertrand Joseph
    Institute of Environmental Medicine, Department of Toxicology, Karolinska Institutet, Box 210, S 171 77 Stockholm, Sweden
    Oncogene 21:65-77. 2002
    ..In NSCLC cells, where the caspase-dependent pathway is less efficient, the triggering of an AIF-mediated caspase-independent mechanism circumvents the resistance of these cells to treatment...
  90. ncbi Killing tumour cells by alkylphosphocholines: evidence for involvement of CD95
    A Matzke
    Forschungszentrum Karlsruhe, Institute for Toxicology and Genetics, Germany
    Eur J Cell Biol 80:1-10. 2001
    ..Experiments with FADD dominant negative cells reveal that induction of apoptosis occurs on the level of CD95 and that these compounds can now be optimised for their capacity to activate the apoptosis-inducing receptor CD95...
  91. ncbi Cytoprotection by Jun kinase during nitric oxide-induced cardiac myocyte apoptosis
    P Andreka
    Department of Molecular and Cellular Pharmacology, University of Miami, FL, USA
    Circ Res 88:305-12. 2001
    ..Early, transient activation of JNK serves both to delay and to reduce the total extent of apoptosis in cardiac myocytes...
  92. ncbi Filamin (280-kDa actin-binding protein) is a caspase substrate and is also cleaved directly by the cytotoxic T lymphocyte protease granzyme B during apoptosis
    K A Browne
    Cancer Immunology Laboratory, Peter MacCallum Cancer Institute, Locked Bag 1, A Beckett Street, Melbourne 8006, Australia
    J Biol Chem 275:39262-6. 2000
    ..Thus, filamin is a functionally important substrate for granzyme B, as its cleavage may account at least partly for caspase-independent cell death mediated by the granzyme...
  93. ncbi Ajoene, an experimental anti-leukemic drug: mechanism of cell death
    V M Dirsch
    Department of Pharmacy, Center of Drug Research, University of Munich, Munich, Germany
    Leukemia 16:74-83. 2002
    ..These results indicate that apoptosis in leukemia cells triggered by ajoene is based on the activation of a mitochondria-dependent caspase cascade which includes also the activation of the initiator caspase-8...
  94. ncbi p38 MAP kinase mediates the cell death induced by PrP106-126 in the SH-SY5Y neuroblastoma cells
    Stefano Thellung
    Department of Oncology, Biology and Genetics, National Institute for Cancer Research IST c o, Genova, Italy
    Neurobiol Dis 9:69-81. 2002
    ..Taken together, our data suggest that the p38 MAP kinase pathway can mediate the SH-SY5Y cell death induced by PrP106-126...
  95. ncbi The c-Myc-interacting adaptor protein Bin1 activates a caspase-independent cell death program
    K Elliott
    The Wistar Institute, Philadelphia, PA, USA
    Oncogene 19:4669-84. 2000
    ..Our findings suggest that the tumor suppressor activity of Bin1 reflects engagement of a unique cell death program. We propose that loss of Bin1 may promote malignancy by blunting death penalties associated with oncogene activation...
  96. ncbi JTE-522-induced apoptosis in human gastric adenocarcinoma [correction of adenocarcinoma] cell line AGS cells by caspase activation accompanying cytochrome C release, membrane translocation of Bax and loss of mitochondrial membrane potential
    Hong Liang Li
    Department of Pharmacology, Jinan University Pharmacy College, Guangzhou 510632, Guangdong Province, China
    World J Gastroenterol 8:217-23. 2002
    ..To investigate the role of the mitochondrial pathway in JTE-522-induced apoptosis and to investigate the relationship between cytochrome C release, caspase activity and loss of mitochondrial membrane potential (Deltapsim)...
  97. ncbi Radiation sensitivity and apoptosis in human lymphoma cells
    J Rudner
    Department of Radiotherapy, , Germany
    Int J Radiat Biol 77:1-11. 2001
    ..The execution phase had no influence on survival, whereas the initiation/decision phase controls immediate survival. However, abrogation of both phases did not influence radiation sensitivity...
  98. ncbi Low concentrations of 1-methyl-4-phenylpyridinium ion induce caspase-mediated apoptosis in human SH-SY5Y neuroblastoma cells
    C Gomez
    Unitat de Bioquimica, Departament de Ciències Fisiològiques II, Universitat de Barcelona, Barcelona, Spain
    J Neurosci Res 63:421-8. 2001
    ....
  99. pmc Dlk/ZIP kinase-induced apoptosis in human medulloblastoma cells: requirement of the mitochondrial apoptosis pathway
    D Kogel
    Interdisciplinary Center for Clinical Research IZKF, Research Group Apoptosis and Cell Death, University of Bonn, Germany
    Br J Cancer 85:1801-8. 2001
    ..Alterations of signal transduction pathways leading to Dlk/ZIP kinase induced apoptosis or loss of expression of upstream activators could play important roles in tumour progression and metastasis of neural tumours...
  100. ncbi Hepatocyte growth factor/scatter factor blocks the mitochondrial pathway of apoptosis signaling in breast cancer cells
    M Gao
    Department of Radiation Oncology, Long Island Jewish Medical Center, Long Island Campus for the Albert Einstein College of Medicine, New Hyde Park, NY 11040, USA
    J Biol Chem 276:47257-65. 2001
    ..These findings suggest that HGF/SF functions, in part, upstream of the mitochondria to block mitochondrial apoptosis signaling, prevent activation of multiple caspases, and protect breast cancer cells against apoptosis...
  101. ncbi Cepharanthine activates caspases and induces apoptosis in Jurkat and K562 human leukemia cell lines
    J Wu
    Department of Immunology, Nagoya University Graduate School of Medicine, Japan
    J Cell Biochem 82:200-14. 2001
    ..Our results suggest that CEP, which does not have bone marrow toxicity, may possess therapeutic potential against human leukemias, including CML, which is resistant to anticancer drugs and radiotherapy...

Research Grants45

  1. Therapeutic effect of boswellin in prostate cancer
    Yongkui Jing; Fiscal Year: 2005
    ..We hope our proposal will lead to the discovery of a novel complementary agent for prostate cancer treatment. ..
  2. Factor XIII Activation and Substrate Specificity
    Muriel C Maurer; Fiscal Year: 2010
    ..Research will focus on understanding how Factor XIII is turned on and how it selects its targets. Studies may lead to novel medical strategies to control the actions of Factor XIII and the resultant clot architecture. ..
  3. CDI and Gamma Delta+ in Viral Myocarditis
    Sally Huber; Fiscal Year: 2005
    ..abstract_text> ..
  4. Retinal Cell Death in Diabetic Retinopathy
    Susanne Mohr; Fiscal Year: 2006
    ..abstract_text> ..
  5. Hypoxia regulates trophoblast giant cell differentiation
    Thomas Brown; Fiscal Year: 2006
    ..Understanding how oxygen signaling mediates trophoblast differentiation will help identify altered mechanisms that could cause preeclampsia. ..
  6. Protein Kinase G Regulation of Granulosa Cell Viability
    John Peluso; Fiscal Year: 2006
    ..We now propose to test this hypothesis using biochemical, genetic, imaging and cell biological techniques. [unreadable] [unreadable]..
  7. Proanthocyanidins: Novel Skin Cancer Preventive Agent
    Santosh Katiyar; Fiscal Year: 2006
    ..Prevention of skin cancer risk will result to protect and prolong the human health and lives. ..
  8. Progesterone regulation of human luteal cell viability
    John Peluso; Fiscal Year: 2006
    ..Such selective manipulation of the P4's actions could have far reaching effects on the treatment for infertility, contraception and certain types of cancers. [unreadable] [unreadable]..
  9. IMAGING APOPTOSIS IN VIVO WITH TECHNETIUM 99M ANNEXIN
    Francis Blankenberg; Fiscal Year: 2007
    ..Completion of this proposal will aid in the design and planning of clinical trials that will study the use of serial annexin V imaging as a non-invasive marker of cellular injury and therapeutic efficacy. ..
  10. Targeting AKT as a novel therapy in pancreatic cancer
    Richard Bold; Fiscal Year: 2007
    ..These results will provide mechanistic as well as pre-clinical data in support of our hypothesis and will allow for the development of novel therapy of human pancreatic cancer. [unreadable] [unreadable] [unreadable]..
  11. Sex in Myocarditis
    Sally Huber; Fiscal Year: 2008
    ..By understanding the factors controlling virus infection and induction of innate immunity, better mechanism for controlling viral disease should be possible. ..
  12. Role of BCL-xL in synaptic plasticity in the hippocampus
    Elizabeth Ann Jonas; Fiscal Year: 2010
    ..We hypothesize that these changes are required for long term changes in synaptic strength after high frequency synaptic stimulation, therefore we plan to test whether inhibition of BClxl prevents l TP. ..
  13. Mitochondrial Oxidative Stress and Protection in Pesticide-induced Neurotoxicity
    Jiyang Cai; Fiscal Year: 2008
    ..Results from these studies will define novel protein targets of oxidative injury and will facilitate our understanding towards the molecular mechanisms of environmental toxicities associated with PD. ..
  14. Prevention of skin cancer by green tea polyphenols
    Santosh Katiyar; Fiscal Year: 2009
    ..Importantly, worldwide interest in green tea as a cancer chemopreventive agent for humans is increasing because it is non-toxic, affordable, popular beverage and is effective in a wide range of organs. ..
  15. scVEGF Targeted Radiotherapy of Mammary and Colonic Cancer
    FRANCIS GERARD BLANKENBERG; Fiscal Year: 2010
    ..Successful completion of our proposal will give the needed preclinical data for pursuing scVEGF targeted radiotherapy in other models and ultimately clinical applications. ..
  16. Prevention of UV-carcinogenesis by antioxidant
    Santosh Katiyar; Fiscal Year: 2004
    ..abstract_text> ..
  17. Conference on Photodynamic Therapy
    David Kessel; Fiscal Year: 2002
    ..The most recent PDT meeting, sponsored by the International Photodynamic Assn, has more than 600 participants. ..
  18. NEUROTROPHINS AND AN ANIMAL MODEL OF FIBROMYALGIA
    ALICE LARSON; Fiscal Year: 2003
    ..If kainic acid activity proves to be a useful model of FMS, therapeutic options may be more readily developed for this disease. ..
  19. 9th International Neurotoxicology Assoc (INA9) Meeting
    Michael Aschner; Fiscal Year: 2003
    ....
  20. Prevention of Photocarcinogenesis by antioxidant
    Santosh Katiyar; Fiscal Year: 2003
    ..abstract_text> ..
  21. T reg Cells in Myocarditis
    Sally A Huber; Fiscal Year: 2010
    ..Determine whether the T reg cells are antigen specific (virus), cardiovascular specific (autoimmunity), or non-antigen specific. ..
  22. IMAGING APOPTOSIS IN VIVO WITH TECHNETIUM 99M ANNEXIN
    Francis Blankenberg; Fiscal Year: 2001
    ..abstract_text> ..
  23. HEMIDESMOSOMAL PROTEIN LINKAGE MAP BY TWO-HYBRID SYSTEM
    Sirpa Aho; Fiscal Year: 2002
    ..abstract_text> ..
  24. Regulation of Oocyte Viability by Granulosa Cell Contact
    John Peluso; Fiscal Year: 2004
    ..abstract_text> ..
  25. Promotion of PDT Induced phototoxicity by bile acids
    David Kessel; Fiscal Year: 2003
    ..If the results of preliminary studies are borne out by further investigation, UDCA could offer a safe and effective means for promoting clinical PDT efficacy. ..
  26. EXTRACELLULAR MATRIX ABNORMALITIES IN CORNEAL EDEMA
    MARIA KENNEY; Fiscal Year: 2002
    ....
  27. SELECTIVE INHIBITION OF HCV TRANSLATION BY TETRAPEPTIDE
    ALEXANDER BIRK; Fiscal Year: 2008
    ..If DAPL or related analogues can be further developed to target and inhibit HCV RNA translation, the clinical application of this kind of therapeutics might be significant. ..
  28. INDUCTION OF MAMMARY CANCER BY SIGNALING MOLECULES
    Steven Anderson; Fiscal Year: 2003
    ..These studies will provide new information about the effect of the prolactin receptor upon mammary epithelial cells, and whether suppression of apoptosis in Important in mammary carcinogenesis. ..
  29. CD4+ T CELLS PROMOTE EARLY ATHEROSCLEROSIS
    Sally Huber; Fiscal Year: 2002
    ..Specific Aim 3 will investigate the role of CD4+ T cells in atherogenesis and evaluate whether these cells promote Th1 cell dominance. ..
  30. MINORITY PREDOCTORAL FELLOWSHIP PROGRAM
    Melanie Mediavilla Varela; Fiscal Year: 2008
    ..These studies will provide insights into the mechanisms underlying prostate tumor resistance to cell death and lead to development of novel therapeutic strategies for PCa. [unreadable] [unreadable] [unreadable]..
  31. Probing Proton Bridges in Catalysis by Thrombin
    ILDIKO KOVACH; Fiscal Year: 2005
    ..A great significance is also to basic understanding of enzyme catalytic power and enzyme-evolutionary theory. ..
  32. Sex in Viral Myocarditis
    Sally Huber; Fiscal Year: 2004
    ..These studies may provide new insights as to how viruses affect developing host defense responses and how hormones can modulate this initial response. ..
  33. Mechanisms of Myocardial Radiofrequency Scar Expansion
    Rupak Mukherjee; Fiscal Year: 2004
    ..abstract_text> ..
  34. Non-Canonical NF-kappaB Signaling In Endothelial Cells
    Michael J May; Fiscal Year: 2010
    ..This proposal will investigate the signals that control blood vessel activation and will therefore identify novel drug targets for preventing or treating chronic inflammation. ..
  35. Abnormalities in Keratoconus Corneas
    MARIA KENNEY; Fiscal Year: 2003
    ..These studies will provide fundamental insights into KC pathogensis and may provide a basis for therapy. ..
  36. Toll-Like Receptors in Bacterial Antigen Induced HIV-LTR
    Ozlem Equils; Fiscal Year: 2004
    ..abstract_text> ..
  37. Divergent Pathways of Cell Death after Brain Injury
    Robert S B Clark; Fiscal Year: 2010
    ..Several unique pathways contribute to overall brain damage. This application seeks to define clinically important pathways, and design novel, sex-based strategies that improve neurological outcome after brain injury. ..
  38. Apoptosis and transport mechanisms in neurodegeneration
    David DeWitt; Fiscal Year: 2002
    ..Cytoskeletal abnormalities including tau phosphorylation, neurofilament accumulation, and microtubule disruption will be examined to determine whether these changes. ..
  39. Safety of Lung Delivered Tissue Plasminogen Activator
    KATHLEEN STRINGER; Fiscal Year: 2006
    ..The proposed Phase II project will complement and extend our Phase I work and will facilitate the development of a promising new, greatly needed therapeutic for the treatment of ARDS. ..
  40. Gender-Specific Treatment of Pediatric Cardiac Arrest
    Robert Clark; Fiscal Year: 2009
    ..abstract_text> ..
  41. Interleukin-1 and Memory Loss in Aging
    Carmelina Gemma; Fiscal Year: 2006
    ....
  42. The effect of nonoxynol-9 on human endometrium
    John Jain; Fiscal Year: 2005
    ..The results of this study will provide important preliminary information on the role of microbicides on endometrial toxicity and may help guide future research priorities. ..
  43. FREE RADICALS AND MUSCLE DYSFUNCTION IN HEART FAILURE
    GERALD SUPINSKI; Fiscal Year: 2005
    ..These data suggest that the proposed experiments should provide important information regarding the pathogenesis of heart failure-related skeletal muscle dysfunction. ..
  44. Universal Vectors for the Therapy of Cancer
    MANUEL PENICHET; Fiscal Year: 2005
    ..The training period will also allow me to attend national and international meetings, both expanding my expertise and my network of collaborators and colleagues. ..
  45. Mifepristone for Prevention of Breakthrough Bleeding
    John Jain; Fiscal Year: 2004
    ..If Mifepristone is shown to safely decrease the incidence of breakthrough bleeding, more women may continue DMPA and not place themselves at risk of an unintended pregnancy. ..