necrosis

Summary

Summary: The pathological process occurring in cells that are dying from irreparable injuries. It is caused by the progressive, uncontrolled action of degradative ENZYMES, leading to MITOCHONDRIAL SWELLING, nuclear flocculation, and cell lysis. Distinguish it from APOPTOSIS which is a normal, regulated cellular process.

Top Publications

  1. ncbi Release of chromatin protein HMGB1 by necrotic cells triggers inflammation
    Paola Scaffidi
    DIBIT, Istituto Scientifico San Raffaele, 20132 Milano, Italy
    Nature 418:191-5. 2002
  2. doi Receptor interacting protein kinase-3 determines cellular necrotic response to TNF-alpha
    Sudan He
    Graduate Program, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
    Cell 137:1100-11. 2009
  3. doi Crosstalk between apoptosis, necrosis and autophagy
    Vassiliki Nikoletopoulou
    Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology Hellas, Heraklion 71110, Crete, Greece
    Biochim Biophys Acta 1833:3448-59. 2013
  4. doi Molecular mechanisms of necroptosis: an ordered cellular explosion
    Peter Vandenabeele
    Department for Molecular Biomedical Research, VIB, Ghent University, Belgium
    Nat Rev Mol Cell Biol 11:700-14. 2010
  5. doi RIP3, an energy metabolism regulator that switches TNF-induced cell death from apoptosis to necrosis
    Duan Wu Zhang
    Key Laboratory of the Ministry of Education for Cell Biology and Tumor Cell Engineering, School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, China
    Science 325:332-6. 2009
  6. pmc Identification of a molecular signaling network that regulates a cellular necrotic cell death pathway
    Junichi Hitomi
    Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA
    Cell 135:1311-23. 2008
  7. pmc Phosphorylation-driven assembly of the RIP1-RIP3 complex regulates programmed necrosis and virus-induced inflammation
    Young Sik Cho
    Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA
    Cell 137:1112-23. 2009
  8. pmc Molecular definitions of cell death subroutines: recommendations of the Nomenclature Committee on Cell Death 2012
    L Galluzzi
    INSERM U848, Apoptosis, Cancer and Immunity, Villejuif, France
    Cell Death Differ 19:107-20. 2012
  9. pmc Apoptosis, pyroptosis, and necrosis: mechanistic description of dead and dying eukaryotic cells
    Susan L Fink
    Department of Laboratory Medicine, University of Washington, Box 357110, Seattle, WA 98195 7110, USA
    Infect Immun 73:1907-16. 2005
  10. doi Mixed lineage kinase domain-like protein mediates necrosis signaling downstream of RIP3 kinase
    Liming Sun
    National Institute of Biological Sciences, 7 Science Park Road, Zhongguancun Life Science Park, Beijing 102206, China
    Cell 148:213-27. 2012

Research Grants

  1. NIH Director's Pioneer Award
    Junying Yuan; Fiscal Year: 2009
  2. Autonomic, Endothelial, and Inflammatory Correlates of Sleep Duration
    MERCEDES RENEE CARNETHON; Fiscal Year: 2012
  3. A Hybrid PARP Inhibitor and Redox Catalyst for Lung Transplantation
    GARRY JOHN SOUTHAN; Fiscal Year: 2012
  4. Ashraf Gorgey; Fiscal Year: 2016
  5. A Redox-active PARP Inhibitor for Lung Transplantation
    ANDREW LURIE SALZMAN; Fiscal Year: 2012
  6. Inhibition of human neutrophil function by Francisella tularensis
    Lee Ann H Allen; Fiscal Year: 2012
  7. Hybrid Optical/Doppler Imaging of Ischemia in NEC - a multicenter trial
    David A Benaron; Fiscal Year: 2010
  8. Robert T Means; Fiscal Year: 2014
  9. David A Bernlohr; Fiscal Year: 2014
  10. A Hybrid Katp Channel Opener to Prevent Radiocontrast-Induced Nephropathy
    Kanneganti Murthy; Fiscal Year: 2012

Detail Information

Publications466 found, 100 shown here

  1. ncbi Release of chromatin protein HMGB1 by necrotic cells triggers inflammation
    Paola Scaffidi
    DIBIT, Istituto Scientifico San Raffaele, 20132 Milano, Italy
    Nature 418:191-5. 2002
    ..Apoptotic cells do not release HMGB1 even after undergoing secondary necrosis and partial autolysis, and thus fail to promote inflammation even if not cleared promptly by phagocytic cells...
  2. doi Receptor interacting protein kinase-3 determines cellular necrotic response to TNF-alpha
    Sudan He
    Graduate Program, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
    Cell 137:1100-11. 2009
    ..However, in several other cell lines, caspase inhibitors switch the apoptotic response to necrosis. A genome wide siRNA screen revealed another member of the RIP kinase family, RIP3, to be required for necrosis...
  3. doi Crosstalk between apoptosis, necrosis and autophagy
    Vassiliki Nikoletopoulou
    Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology Hellas, Heraklion 71110, Crete, Greece
    Biochim Biophys Acta 1833:3448-59. 2013
    Apoptosis and necrosis are the two major modes of cell death, the molecular mechanisms of which have been extensively studied...
  4. doi Molecular mechanisms of necroptosis: an ordered cellular explosion
    Peter Vandenabeele
    Department for Molecular Biomedical Research, VIB, Ghent University, Belgium
    Nat Rev Mol Cell Biol 11:700-14. 2010
    ..was considered the sole form of programmed cell death during development, homeostasis and disease, whereas necrosis was regarded as an unregulated and uncontrollable process...
  5. doi RIP3, an energy metabolism regulator that switches TNF-induced cell death from apoptosis to necrosis
    Duan Wu Zhang
    Key Laboratory of the Ministry of Education for Cell Biology and Tumor Cell Engineering, School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, China
    Science 325:332-6. 2009
    b>Necrosis can be induced by stimulating death receptors with tumor necrosis factor (TNF) or other agonists; however, the underlying mechanism differentiating necrosis from apoptosis is largely unknown...
  6. pmc Identification of a molecular signaling network that regulates a cellular necrotic cell death pathway
    Junichi Hitomi
    Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA
    Cell 135:1311-23. 2008
    ..Our study defines a cellular signaling network that regulates necroptosis and the molecular bifurcation that controls apoptosis and necroptosis...
  7. pmc Phosphorylation-driven assembly of the RIP1-RIP3 complex regulates programmed necrosis and virus-induced inflammation
    Young Sik Cho
    Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA
    Cell 137:1112-23. 2009
    Programmed necrosis is a form of caspase-independent cell death whose molecular regulation is poorly understood...
  8. pmc Molecular definitions of cell death subroutines: recommendations of the Nomenclature Committee on Cell Death 2012
    L Galluzzi
    INSERM U848, Apoptosis, Cancer and Immunity, Villejuif, France
    Cell Death Differ 19:107-20. 2012
    ..cell death morphologies and for the appropriate use of cell death-related terminology, including 'apoptosis', 'necrosis' and 'mitotic catastrophe'...
  9. pmc Apoptosis, pyroptosis, and necrosis: mechanistic description of dead and dying eukaryotic cells
    Susan L Fink
    Department of Laboratory Medicine, University of Washington, Box 357110, Seattle, WA 98195 7110, USA
    Infect Immun 73:1907-16. 2005
  10. doi Mixed lineage kinase domain-like protein mediates necrosis signaling downstream of RIP3 kinase
    Liming Sun
    National Institute of Biological Sciences, 7 Science Park Road, Zhongguancun Life Science Park, Beijing 102206, China
    Cell 148:213-27. 2012
    The receptor-interacting serine-threonine kinase 3 (RIP3) is a key signaling molecule in the programmed necrosis (necroptosis) pathway...
  11. doi PVP-coated silver nanoparticles and silver ions induce reactive oxygen species, apoptosis and necrosis in THP-1 monocytes
    Rasmus Foldbjerg
    Department of Environmental and Occupational Medicine, Institute of Public Health, Aarhus University, Bartholins Alle 2, Bygn 1260, 8000 Aarhus, Denmark
    Toxicol Lett 190:156-62. 2009
    ..the flowcytometric annexin V/propidium iodide (PI) assay, both Ag NPs and Ag+ were shown to induce apoptosis and necrosis in THP-1 cells depending on dose and exposure time...
  12. pmc Identification of a dendritic cell receptor that couples sensing of necrosis to immunity
    David Sancho
    Immunobiology Laboratory, London Research Institute, Lincoln s Inn Fields Laboratories, 44 Lincoln s Inn Fields, London WC2A 3PX, UK
    Nature 458:899-903. 2009
    ..antigens present in necrotic cells can sometimes provoke a specific immune response and it has been argued that necrosis could explain adaptive immunity in seemingly infection-free situations, such as after allograft transplantation ..
  13. doi Programmed necrosis: backup to and competitor with apoptosis in the immune system
    Jiahuai Han
    State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, China
    Nat Immunol 12:1143-9. 2011
    ..Studies have demonstrated that in addition to caspase-dependent apoptosis, necrosis dependent on the kinases RIP1 and RIP3 (also called necroptosis) is a major programmed cell-death pathway in ..
  14. ncbi Necrotic death as a cell fate
    Wei Xing Zong
    Department of Molecular Genetics and Microbiology, State University of New York at Stony Brook, New York 11794, USA
    Genes Dev 20:1-15. 2006
    ..This form of tissue damage was termed "necrosis", derived from the Greek "nekros" for corpse...
  15. pmc Caspase 8 inhibits programmed necrosis by processing CYLD
    Marie Anne O'Donnell
    Immunology Institute, Mount Sinai School of Medicine, New York, New York 10029, USA
    Nat Cell Biol 13:1437-42. 2011
    ..1). However, the dominant function of caspase 8 is to transmit a pro-survival signal that suppresses programmed necrosis (or necroptosis) mediated by RIPK1 and RIPK3 (refs 2-6) during embryogenesis and haematopoiesis(7-9)...
  16. pmc Many stimuli pull the necrotic trigger, an overview
    N Vanlangenakker
    Department for Molecular Biomedical Research, VIB, Zwijnaarde Ghent, Belgium
    Cell Death Differ 19:75-86. 2012
    ..Because of this pioneer finding, regulated necrosis and in particular RIPK1/RIPK3 kinase-mediated necrosis, referred to as necroptosis, has become an intensively ..
  17. doi The mitochondrial phosphatase PGAM5 functions at the convergence point of multiple necrotic death pathways
    Zhigao Wang
    Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA
    Cell 148:228-43. 2012
    The programmed necrosis induced by TNF-α requires the activities of the receptor-interacting serine-threonine kinases RIP1 and RIP3 and their interaction with the mixed lineage kinase domain-like protein MLKL...
  18. ncbi Cell death by necrosis: towards a molecular definition
    Pierre Golstein
    Centre d immunologie de Marseille Luminy, Universite de la Mediterranee, Case 906, 13288 Marseille Cedex 9, France
    Trends Biochem Sci 32:37-43. 2007
    b>Necrosis has been defined as a type of cell death that lacks the features of apoptosis and autophagy, and is usually considered to be uncontrolled...
  19. doi Necroptosis, necrosis and secondary necrosis converge on similar cellular disintegration features
    T Vanden Berghe
    Department for Molecular Biomedical Research, VIB, Ghent, Belgium
    Cell Death Differ 17:922-30. 2010
    Necroptosis, necrosis and secondary necrosis following apoptosis represent different modes of cell death that eventually result in similar cellular morphology including rounding of the cell, cytoplasmic swelling, rupture of the plasma ..
  20. pmc Mixed lineage kinase domain-like is a key receptor interacting protein 3 downstream component of TNF-induced necrosis
    Jie Zhao
    Cell and Cancer Biology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 109:5322-7. 2012
    Tumor necrosis factor (TNF) is an important inflammatory cytokine and induces many cellular responses, including inflammation, cell proliferation, apoptosis, and necrosis...
  21. pmc The RIP1/RIP3 necrosome forms a functional amyloid signaling complex required for programmed necrosis
    Jixi Li
    Department of Biochemistry, Weill Cornell Medical College, New York, NY 10065, USA
    Cell 150:339-50. 2012
    RIP1 and RIP3 kinases are central players in TNF-induced programmed necrosis. Here, we report that the RIP homotypic interaction motifs (RHIMs) of RIP1 and RIP3 mediate the assembly of heterodimeric filamentous structures...
  22. ncbi Fas triggers an alternative, caspase-8-independent cell death pathway using the kinase RIP as effector molecule
    N Holler
    Institute of Biochemistry, University of Lausanne, BIL Biomedical Research Center, Chemin des Boveresses 155, CH 1066 Epalinges, Switzerland
    Nat Immunol 1:489-95. 2000
    Cell death is achieved by two fundamentally different mechanisms: apoptosis and necrosis. Apoptosis is dependent on caspase activation, whereas the caspase-independent necrotic signaling pathway remains largely uncharacterized...
  23. pmc A family of conserved bacterial effectors inhibits salicylic acid-mediated basal immunity and promotes disease necrosis in plants
    Sruti DebRoy
    Cell and Molecular Biology Program and Department of Energy Plant Research Laboratory, Michigan State University, East Lansing, MI 48824, USA
    Proc Natl Acad Sci U S A 101:9927-32. 2004
    ..and dspA/E mutants was linked to their inability to suppress cell wall-based defenses and to cause normal disease necrosis in Arabidopsis and apple host plants...
  24. pmc Disruption of the Cbfa2 gene causes necrosis and hemorrhaging in the central nervous system and blocks definitive hematopoiesis
    Q Wang
    Department of Biochemistry, Dartmouth Medical School, Hanover, NH 03755, USA
    Proc Natl Acad Sci U S A 93:3444-9. 1996
    ..Hemorrhaging is preceded by symmetric, bilateral necrosis in these regions...
  25. pmc Mycobacterium tuberculosis evades macrophage defenses by inhibiting plasma membrane repair
    Maziar Divangahi
    Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts, USA
    Nat Immunol 10:899-906. 2009
    Induction of macrophage necrosis is a strategy used by virulent Mycobacterium tuberculosis (Mtb) to avoid innate host defense...
  26. ncbi mRNA is an endogenous ligand for Toll-like receptor 3
    Katalin Kariko
    Division of Neurosurgery and Infectious Diseases, University of Pennsylvania, 3610 Hamilton Walk, Philadelphia, PA 19104, USA
    J Biol Chem 279:12542-50. 2004
    ..natural or 2'-fluoro-substituted mRNA induced the expression of TLR3, interferon regulatory factor-1, tumor necrosis factor-alpha, and interleukin-1 receptor-associated kinase-M mRNA in human dendritic cells (DCs)...
  27. pmc Catalytic activity of the caspase-8-FLIP(L) complex inhibits RIPK3-dependent necrosis
    Andrew Oberst
    Dept of Immunology, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Nature 471:363-7. 2011
    ..has a survival activity, as it is required for embryonic development, T-lymphocyte activation, and resistance to necrosis induced by tumour necrosis factor-α (TNF-α) and related family ligands...
  28. pmc DAI/ZBP1/DLM-1 complexes with RIP3 to mediate virus-induced programmed necrosis that is targeted by murine cytomegalovirus vIRA
    Jason W Upton
    Department of Microbiology and Immunology, Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322, USA
    Cell Host Microbe 11:290-7. 2012
    Programmed necrosis, like apoptosis, eliminates pathogen-infected cells as a component of host defense...
  29. doi Programmed necrosis from molecules to health and disease
    Lorenzo Galluzzi
    INSERM, Villejuif, France
    Int Rev Cell Mol Biol 289:1-35. 2011
    ..death researchers have witnessed a gradual but deep conceptual revolution: it has been unequivocally shown that necrosis, which for long had been considered as a purely accidental cell death mode, can also be induced by finely ..
  30. pmc Caspase-8 regulates TNF-α-induced epithelial necroptosis and terminal ileitis
    Claudia Günther
    Department of Medicine 1, Friedrich Alexander University, D 91054 Erlangen, Germany
    Nature 477:335-9. 2011
    ..Epithelial cell death was induced by tumour necrosis factor (TNF)-α, was associated with increased expression of receptor-interacting protein 3 (Rip3; also known as ..
  31. ncbi Morphologic and biochemical hallmarks of apoptosis
    A Saraste
    Department of Anatomy, University of Turku, Finland
    Cardiovasc Res 45:528-37. 2000
    ..Recently, potentially more specific assays based on analysis of DNA fragmentation or demonstration of caspase activation have been developed. Applicability of these assays to demonstrate cardiomyocyte apoptosis should be tested...
  32. ncbi Four deaths and a funeral: from caspases to alternative mechanisms
    M Leist
    H Lundbeck A S, Ottiliavej 9, DK 2500 Copenhagen Valby, Denmark
    Nat Rev Mol Cell Biol 2:589-98. 2001
    ....
  33. ncbi The roles of therapy-induced autophagy and necrosis in cancer treatment
    Ravi K Amaravadi
    Abramson Cancer Center at the University of Pennsylvania, Philadelphia, PA 19104, USA
    Clin Cancer Res 13:7271-9. 2007
    ..modalities in cancer treatment, only recently has the regulation and significance of tumor cell autophagy and necrosis become the focus of investigations. Necrosis is an irreversible inflammatory form of cell death...
  34. doi The role of the kinases RIP1 and RIP3 in TNF-induced necrosis
    Peter Vandenabeele
    Molecular Signaling and Cell Death Unit, Department for Molecular Biomedical Research, VIB, 9052 Zwijnaarde, Belgium
    Sci Signal 3:re4. 2010
    Tumor necrosis factor (TNF) is a pleiotropic molecule with a crucial role in cellular stress and inflammation during infection, tissue damage, and cancer...
  35. pmc Antisense correction of SMN2 splicing in the CNS rescues necrosis in a type III SMA mouse model
    Yimin Hua
    Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA
    Genes Dev 24:1634-44. 2010
    ..prerequisite for disease treatment--and its ability to rescue a mild SMA mouse model that develops tail and ear necrosis, resembling the distal tissue necrosis reported in some SMA infants...
  36. ncbi Suppression of human prostate tumor growth in mice by a cytolytic D-, L-amino Acid Peptide: membrane lysis, increased necrosis, and inhibition of prostate-specific antigen secretion
    Niv Papo
    Department of Biological Chemistry, The Weizmann Institute of Science, Rehovot, Israel
    Cancer Res 64:5779-86. 2004
    ....
  37. doi Apoptosis and necrosis: detection, discrimination and phagocytosis
    Dmitri V Krysko
    Molecular Signaling and Cell Death Unit, Department for Molecular Biomedical Research, VIB, 9052 Ghent, Belgium
    Methods 44:205-21. 2008
    ..of cell death have been described: apoptosis (type I), cell death associated with autophagy (type II) and necrosis (type III). Apoptosis and cell death associated with autophagy can be distinguished by certain biochemical events...
  38. pmc Necrotic cells trigger a sterile inflammatory response through the Nlrp3 inflammasome
    Shankar S Iyer
    Division of Infectious Diseases, Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA
    Proc Natl Acad Sci U S A 106:20388-93. 2009
    ..animals against mortality, renal dysfunction, and neutrophil influx in an in vivo renal ischemic acute tubular necrosis model...
  39. pmc Differential regulation of caspase-1 activation, pyroptosis, and autophagy via Ipaf and ASC in Shigella-infected macrophages
    Toshihiko Suzuki
    Division of Bacterial Pathogenesis, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan
    PLoS Pathog 3:e111. 2007
    ..Furthermore, the absence of Ipaf or caspase-1, but not ASC, regulates pyroptosis and the induction of autophagy in Shigella-infected macrophages, providing a novel function for NLR proteins in bacterial-host interactions...
  40. ncbi Cyclophilin D-dependent mitochondrial permeability transition regulates some necrotic but not apoptotic cell death
    Takashi Nakagawa
    Laboratory of Molecular Genetics, Department of Post Genomics and Diseases, Japan Science and Technology Corporation, 2 2 Yamadaoka, Suita, Osaka 565 0871, Japan
    Nature 434:652-8. 2005
    ..In apoptosis and necrosis, the mitochondrial permeability transition (mPT), which leads to disruption of the mitochondrial membranes and ..
  41. pmc IL-1beta receptor blockade protects islets against pro-inflammatory cytokine induced necrosis and apoptosis
    Alice Schwarznau
    Department of Surgery, Technical University of Munich, Munich, Germany
    J Cell Physiol 220:341-7. 2009
    ..cytokines (PIC) impair islet viability and function by activating inflammatory pathways that induce both necrosis and apoptosis...
  42. doi Tumor necrosis is a new promising prognostic factor in colorectal cancer
    Marion J Pollheimer
    Institute of Pathology, Medical University, Auenbruggerplatz 25, Graz, Austria
    Hum Pathol 41:1749-57. 2010
    The prognostic significance of tumor necrosis in colorectal cancer is unclear...
  43. pmc Metabolic targeting of lactate efflux by malignant glioma inhibits invasiveness and induces necrosis: an in vivo study
    Chaim B Colen
    Department of Neurological Surgery, Wayne State University School of Medicine, Detroit, MI 48201, USA
    Neoplasia 13:620-32. 2011
    ..Convection-enhanced delivery of inhibitor to the tumor bed caused tumor necrosis, with 50% of the animals surviving beyond the experimental end points (3 months after inhibitor exhaustion)...
  44. doi Prognostic value of tumour necrosis and host inflammatory responses in colorectal cancer
    C H Richards
    University Department of Surgery, Glasgow Royal Infirmary, Glasgow, UK
    Br J Surg 99:287-94. 2012
    Tumour necrosis is a marker of poor prognosis in some tumours but the mechanism is unclear. This study examined the prognostic value of tumour necrosis and host inflammatory responses in colorectal cancer.
  45. doi Inhibition of RIP1-dependent necrosis prevents adverse cardiac remodeling after myocardial ischemia-reperfusion in vivo
    Martinus I F J Oerlemans
    Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands
    Basic Res Cardiol 107:270. 2012
    Accumulating evidence indicates that programmed necrosis plays a critical role in cell death during ischemia-reperfusion...
  46. pmc Chrysophanol induces necrosis through the production of ROS and alteration of ATP levels in J5 human liver cancer cells
    Chi Cheng Lu
    Department of Life Sciences, National Chung Hsing University, Taichung, Taiwan
    Mol Nutr Food Res 54:967-76. 2010
    ..goal of this study was to examine if chrysophanol had cytotoxic effects and if such effects involved apoptosis or necrosis in J5 human liver cancer cells. Chrysophanol induced necrosis in J5 cells in a dose- and time-dependent manner...
  47. pmc Inhibition of Eyes Absent Homolog 4 expression induces malignant peripheral nerve sheath tumor necrosis
    S J Miller
    Department of Pediatrics, Division of Experimental Hematology and Cancer Biology, Cincinnati Children s Hospital Research Foundation, University of Cincinnati College of Medicine, Cincinnati, OH 45229 3039, USA
    Oncogene 29:368-79. 2010
    ..suppression of EYA4 expression using short hairpin RNA reduced cell adhesion and migration and caused cellular necrosis without affecting cell proliferation or apoptotic cell death...
  48. pmc Critical role for NLRP3 in necrotic death triggered by Mycobacterium tuberculosis
    Ka Wing Wong
    Howard Hughes Medical Institute, Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
    Cell Microbiol 13:1371-84. 2011
    ..The ESX-1 secretion system and its substrate ESAT-6 are required for M. tuberculosis to induce necrosis, but host factors that mediate the ESAT-6-promoted necrosis remain unknown...
  49. pmc RIP1-dependent and independent effects of necrostatin-1 in necrosis and T cell activation
    Youngsik Cho
    Department of Pathology, Program in Immunology and Virology, The University of Massachusetts Medical School, Worcester, Massachusetts, United States of America
    PLoS ONE 6:e23209. 2011
    Programmed necrosis/necroptosis is an emerging form of cell death that plays important roles in mammalian development and the immune system...
  50. ncbi Poly(ADP-ribose) polymerase-1 signaling to mitochondria in necrotic cell death requires RIP1/TRAF2-mediated JNK1 activation
    Yue Xu
    Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA
    J Biol Chem 281:8788-95. 2006
    Poly(ADP-ribose) polymerase-1 (PARP-1) hyperactivation-induced necrosis has been implicated in several pathophysiological conditions...
  51. ncbi Cell death modalities: classification and pathophysiological implications
    L Galluzzi
    INSERM, Unit Apoptosis, Cancer and Immunity, Villejuif, France
    Cell Death Differ 14:1237-43. 2007
  52. doi Loss of peroxisome function triggers necrosis
    Helmut Jungwirth
    Institute of Molecular Biosciences IMB, University of Graz, Austria
    FEBS Lett 582:2882-6. 2008
    ..death of ageing-like yeast cells lacking PEX6 does not depend on the apoptotic key players Yca1p and Aif1p, but instead shows markers of necrosis. Thus, we conclude that loss of peroxisomal function leads to a form of necrotic cell death.
  53. ncbi Cell death: critical control points
    Nika N Danial
    Howard Hughes Medical Institute, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Cell 116:205-19. 2004
    ..The identification of critical control points in the cell death pathway has yielded fundamental insights for basic biology, as well as provided rational targets for new therapeutics...
  54. ncbi Regulation of cell death: the calcium-apoptosis link
    Sten Orrenius
    Institute of Environmental Medicine, Division of Toxicology, Karolinska Institutet, Box 210, SE 171 77 Stockholm, Sweden
    Nat Rev Mol Cell Biol 4:552-65. 2003
    ..However, more recently it has become clear that cellular Ca2+ overload, or perturbation of intracellular Ca2+ compartmentalization, can cause cytotoxicity and trigger either apoptotic or necrotic cell death...
  55. pmc HMGB1 is an endogenous immune adjuvant released by necrotic cells
    Patrizia Rovere-Querini
    Cancer Immunotherapy and Gene Therapy Program, Clinical Immunology Unit H San Raffaele Scientific Institute and Vita Salute San Raffaele University, DIBIT 3A1, Chromatin Dynamics Unit, Via Olgettina 58, 20132 Milano, Italy
    EMBO Rep 5:825-30. 2004
    ..In vivo, HMGB1 enhances the primary antibody responses to soluble antigens and transforms poorly immunogenic apoptotic lymphoma cells into efficient vaccines...
  56. pmc RIP3 mediates the embryonic lethality of caspase-8-deficient mice
    William J Kaiser
    Department of Microbiology and Immunology, Emory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia 30322, USA
    Nature 471:368-72. 2011
    ..Thus, Casp8 contributes to homeostatic control in the adult immune system; however, RIP3 and Casp8 are together completely dispensable for mammalian development...
  57. pmc Reduced apoptosis and plaque necrosis in advanced atherosclerotic lesions of Apoe-/- and Ldlr-/- mice lacking CHOP
    Edward Thorp
    Department of Medicine, Columbia University, New York, NY 10032, USA
    Cell Metab 9:474-81. 2009
    ..vitro studies have implicated the ER stress effector CHOP in macrophage apoptosis, a process involved in plaque necrosis in advanced atheromata...
  58. pmc Autophagy promotes necrosis in apoptosis-deficient cells in response to ER stress
    E Ullman
    Cell Death Differ 15:422-5. 2008
  59. ncbi Death by design: apoptosis, necrosis and autophagy
    Aimee L Edinger
    University of Pennsylvania, Abramson Family Cancer Research Institute, 450 BRB II III, 421 Curie Blvd, Philadelphia, Pennsylvania 19104, USA
    Curr Opin Cell Biol 16:663-9. 2004
    ..Recently, necrosis, once thought of as simply a passive, unorganized way to die, has emerged as an alternate form of programmed cell ..
  60. ncbi Apoptosis and necrosis in the liver: a tale of two deaths?
    Harmeet Malhi
    Department of Medicine, Mayo Clinic College of Medicine, Rochester, MN, USA
    Hepatology 43:S31-44. 2006
    ..Cell death typically follows one of two patterns: oncotic necrosis and apoptosis...
  61. pmc TLR3 is an endogenous sensor of tissue necrosis during acute inflammatory events
    Karen A Cavassani
    Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA
    J Exp Med 205:2609-21. 2008
    ..However, the levels of inflammatory chemokines and tumor necrosis factor alpha quickly returned to baseline in tlr3(-/-) mice, and these mice were protected from the lethal ..
  62. doi Mitochondrial permeability transition in Ca(2+)-dependent apoptosis and necrosis
    Andrea Rasola
    Department of Biomedical Sciences and CNR Institute of Neuroscience, University of Padova, Italy
    Cell Calcium 50:222-33. 2011
    ....
  63. doi Apoptosis, necrosis and necroptosis: cell death regulation in the intestinal epithelium
    Claudia Günther
    Department of Medicine, University of Erlangen Nuremberg, Hartmannstrasse 14, 91 054 Erlangen, Germany
    Gut 62:1062-71. 2013
    ..The following article reviews previous studies on cell death regulation in IEC and a potential role of necroptosis for gut homeostasis...
  64. doi Autophagy, apoptosis, mitoptosis and necrosis: interdependence between those pathways and effects on cancer
    Wiem Chaabane
    Division of Cell Biology, Department Clinical and Experimental Medicine IKE, and Integrative Regenerative Medicine Center IGEN, Linkoping University, Cell Biology Building, Linkoping, Sweden
    Arch Immunol Ther Exp (Warsz) 61:43-58. 2013
    ..the role of caspases in cell death forms, we offer insight into the interplay between autophagy and apoptosis, or necrosis, where autophagy may initially serve pro-survival functions...
  65. pmc Intracellular interleukin-1 receptor 2 binding prevents cleavage and activity of interleukin-1α, controlling necrosis-induced sterile inflammation
    Yue Zheng
    Division of Cardiovascular Medicine, Department of Medicine, University of Cambridge, Addenbrooke s Hospital, Cambridge CB2 0QQ, UK
    Immunity 38:285-95. 2013
    b>Necrosis can induce profound inflammation or be clinically silent. However, the mechanisms underlying such tissue specificity are unknown...
  66. pmc TNF-induced necroptosis and PARP-1-mediated necrosis represent distinct routes to programmed necrotic cell death
    Justyna Sosna
    Institut fur Immunologie, Christian Albrechts Universitat zu Kiel, Michaelisstr 5, 24105, Kiel, Germany
    Cell Mol Life Sci 71:331-48. 2014
    Programmed necrosis is important in many (patho)physiological settings...
  67. doi Regulated necrosis: the expanding network of non-apoptotic cell death pathways
    Tom Vanden Berghe
    1 Molecular Signaling and Cell Death Unit, Inflammation Research Center, Flanders Institute for Biotechnology VIB, Ghent University, 9052 Ghent, Belgium 2
    Nat Rev Mol Cell Biol 15:135-47. 2014
    Cell death research was revitalized by the understanding that necrosis can occur in a highly regulated and genetically controlled manner...
  68. ncbi A role for tumor necrosis factor receptor-2 and receptor-interacting protein in programmed necrosis and antiviral responses
    Francis Ka Ming Chan
    Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 278:51613-21. 2003
    Members of the tumor necrosis factor (TNF) receptor (TNFR) superfamily are potent regulators of apoptosis, a process that is important for the maintenance of immune homeostasis...
  69. pmc Genetic control of necrosis - another type of programmed cell death
    Kimberly McCall
    Department of Biology, Boston University, Boston, MA 02215, USA
    Curr Opin Cell Biol 22:882-8. 2010
    b>Necrosis has been thought to be an accidental or uncontrolled type of cell death rather than programmed...
  70. doi Class A scavenger receptor attenuates myocardial infarction-induced cardiomyocyte necrosis through suppressing M1 macrophage subset polarization
    Yulong Hu
    Atherosclerosis Research Center, Key Laboratory of Cardiovascular Disease and Molecular Intervention, Nanjing Medical University, Nanjing 210029, China
    Basic Res Cardiol 106:1311-28. 2011
    ..a key modulator of inflammation, may steer macrophage polarization, which in turn influences cardiomyocytes necrosis after MI...
  71. pmc Mycobacterium tuberculosis blocks crosslinking of annexin-1 and apoptotic envelope formation on infected macrophages to maintain virulence
    Huixian Gan
    Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    Nat Immunol 9:1189-97. 2008
    ..by proteolysis, thus preventing completion of the apoptotic envelope, which resulted in macrophage death by necrosis. Virulent M...
  72. doi Gold nanoparticles of diameter 1.4 nm trigger necrosis by oxidative stress and mitochondrial damage
    Yu Pan
    Biomedical Engineering, Biointerface Laboratory, RWTH Aachen University, Aachen, Germany
    Small 5:2067-76. 2009
    ..The caspase inhibitor Z-VAD-fmk does not rescue the cells, which suggests that necrosis, not apoptosis, is the predominant pathway at this concentration...
  73. ncbi Mitochondrial permeability transition: a common pathway to necrosis and apoptosis
    Jae Sung Kim
    Department of Cell and Developmental Biology, University of North Carolina at Chapel Hill, CB 7090, 236 Taylor Hall, Chapel Hill, NC 27599 7090, USA
    Biochem Biophys Res Commun 304:463-70. 2003
    ..The MPT is a causative event, leading to necrosis and apoptosis in hepatocytes after oxidative stress, Ca(2+) toxicity, and ischemia/reperfusion...
  74. ncbi Apoptosis versus oncotic necrosis in hepatic ischemia/reperfusion injury
    Hartmut Jaeschke
    Liver Research Institute, University of Arizona, College of Medicine, Room 6309, 1501 N Campbell Avenue, Tucson, Arizona, USA
    Gastroenterology 125:1246-57. 2003
    ..Here, we review the mechanisms underlying adenosine triphosphate depletion-dependent oncotic necrosis and caspase-dependent apoptosis, with emphasis on shared features and pathways...
  75. ncbi Fatty acids trigger mitochondrion-dependent necrosis
    Patrick Rockenfeller
    University of Graz, Institute for Molecular Biosciences, Austria
    Cell Cycle 9:2836-42. 2010
    ..FFA-mediated necrosis depends on functional mitochondria and leads to the accumulation of reactive oxygen species...
  76. pmc cIAP1 and TAK1 protect cells from TNF-induced necrosis by preventing RIP1/RIP3-dependent reactive oxygen species production
    N Vanlangenakker
    Department for Molecular Biomedical Research, VIB, Technologiepark 927, Zwijnaarde Ghent 9052, Belgium
    Cell Death Differ 18:656-65. 2011
    ..RIP1 is also a regulator of necrosis, a caspase-independent type of cell death...
  77. ncbi Cell death independent of caspases: a review
    Linda E Bröker
    Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands
    Clin Cancer Res 11:3155-62. 2005
    ..have been divided into apoptosis, which is actively executed by specific proteases, the caspases, and accidental necrosis. However, there is now accumulating evidence indicating that cell death can occur in a programmed fashion but in ..
  78. ncbi Necrosis, a well-orchestrated form of cell demise: signalling cascades, important mediators and concomitant immune response
    Nele Festjens
    Molecular Signalling and Cell Death Unit, Department for Molecular Biomedical Research, VIB and Ghent University, Fiers Schell Van Montagu Building, Technologiepark 927, B 9052 Ghent, Belgium
    Biochim Biophys Acta 1757:1371-87. 2006
    b>Necrosis has long been described as a consequence of physico-chemical stress and thus accidental and uncontrolled...
  79. pmc Necroptosis as an alternative form of programmed cell death
    Dana E Christofferson
    Department of Cell Biology, Harvard Medical School, 240 Longwood Ave, Boston, MA 02115, United States
    Curr Opin Cell Biol 22:263-8. 2010
    ..survival or inducing apoptosis to lead to cell death; and now a third pathway, termed necroptosis or programmed necrosis has been identified...
  80. doi FADD prevents RIP3-mediated epithelial cell necrosis and chronic intestinal inflammation
    Patrick Simon Welz
    Institute for Genetics, Centre for Molecular Medicine, University of Cologne, Zülpicher Str 47a, 50674 Cologne, Germany
    Nature 477:330-4. 2011
    ..an adaptor protein required for death-receptor-induced apoptosis, spontaneously developed epithelial cell necrosis, loss of Paneth cells, enteritis and severe erosive colitis...
  81. doi The adaptor protein FADD protects epidermal keratinocytes from necroptosis in vivo and prevents skin inflammation
    Marion C Bonnet
    Institute for Genetics, Center for Molecular Medicine, and Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases, University of Cologne, Zülpicher Str 47a, 50674 Cologne, Germany
    Immunity 35:572-82. 2011
    ..The development of skin inflammation in FADD(E-KO) mice was triggered by RIP kinase 3 (RIP3)-mediated programmed necrosis (termed necroptosis) of FADD-deficient keratinocytes, which was partly dependent on the deubiquitinating enzyme ..
  82. doi RIP kinase-dependent necrosis drives lethal systemic inflammatory response syndrome
    Linde Duprez
    Department for Molecular Biomedical Research, the Flanders Institute for Biotechnology VIB, 9052 Ghent, Belgium
    Immunity 35:908-18. 2011
    Engagement of tumor necrosis factor receptor 1 signals two diametrically opposed pathways: survival-inflammation and cell death...
  83. pmc Poly(ADP-ribose) polymerase is a mediator of necrotic cell death by ATP depletion
    H C Ha
    Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Proc Natl Acad Sci U S A 96:13978-82. 1999
    ..In this study, we have differentially elicited apoptosis or necrosis in mouse fibroblasts...
  84. ncbi Rapid, noninflammatory and PS-dependent phagocytic clearance of necrotic cells
    U A Hirt
    Faculty of Biology, University of Konstanz, X911, D 78457 Konstanz, Germany
    Cell Death Differ 10:1156-64. 2003
    ..We demonstrate that this can occur independently of calcium signals, and that surface phosphatidylserine is essential for the uptake of necrotic cells by both human macrophages and murine microglia...
  85. ncbi A mechanism of virulence: virulent Mycobacterium tuberculosis strain H37Rv, but not attenuated H37Ra, causes significant mitochondrial inner membrane disruption in macrophages leading to necrosis
    Minjian Chen
    Division of Rheumatology Immunology, Department of Medicine, Medical Research Center Brigham and Women s Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA
    J Immunol 176:3707-16. 2006
    ..of infection leads 48-72 h after the infection to cell death with the characteristics of apoptosis or necrosis. Predominant induction of one or the other cell death modality depends on differences in mitochondrial membrane ..
  86. pmc Autophagy promotes tumor cell survival and restricts necrosis, inflammation, and tumorigenesis
    Kurt Degenhardt
    Center for Advanced Biotechnology and Medicine, 679 Hoes Lane, Piscataway, New Jersey 08854, USA
    Cancer Cell 10:51-64. 2006
    ..autophagy under conditions of nutrient limitation can restore cell death to apoptosis-refractory tumors, but this necrosis is associated with inflammation and accelerated tumor growth...
  87. ncbi Shikonin circumvents cancer drug resistance by induction of a necroptotic death
    Weidong Han
    Cancer Institute, The Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou, Zhejiang, China
    Mol Cancer Ther 6:1641-9. 2007
    ..To our best knowledge, this is the first report to document the induction of necroptosis by a small molecular compound to circumvent cancer drug resistance...
  88. ncbi TNF-induced activation of the Nox1 NADPH oxidase and its role in the induction of necrotic cell death
    You Sun Kim
    Cell and Cancer Biology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Mol Cell 26:675-87. 2007
    Tumor necrosis factor (TNF) is an important cytokine in immunity and inflammation and induces many cellular responses, including apoptosis and necrosis...
  89. pmc Toll-like receptors activate programmed necrosis in macrophages through a receptor-interacting kinase-3-mediated pathway
    Sudan He
    Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, First Affiliated Hospital, Soochow University, Suzhou 215123, China
    Proc Natl Acad Sci U S A 108:20054-9. 2011
    ..We report here that mouse macrophages undergo receptor-interacting kinase-3 (RIP3)-dependent but TNF-α-independent necrosis when Toll-like receptors (TLR) 3 and 4 are activated by poly(I:C) and LPS, respectively...
  90. pmc Toll-like receptor 3-mediated necrosis via TRIF, RIP3, and MLKL
    William J Kaiser
    From the Department of Microbiology and Immunology, Emory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia 30322
    J Biol Chem 288:31268-79. 2013
    ..of TLR2, TLR3, TLR4, TLR5, or TLR9 results in receptor interacting protein (RIP) 3 kinase-dependent programmed necrosis that occurs through either TIR domain-containing adapter-inducing interferon-β (TRIF) or MyD88 signal ..
  91. pmc Receptor interacting protein kinase-mediated necrosis contributes to cone and rod photoreceptor degeneration in the retina lacking interphotoreceptor retinoid-binding protein
    Kota Sato
    Department of Ophthalmology and Neuroscience Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112, Electron Microscope Laboratory, Tulane University, New Orleans, Louisiana 70118, Department of Ophthalmology, Georgia Health Sciences University, Augusta, Georgia 30912, and Jules Stein Eye Institute, The University of California, Los Angeles School of Medicine, Los Angeles, California 90095
    J Neurosci 33:17458-68. 2013
    ..Here, we show that amounts of tumor necrosis factor-α (TNF-α) in the interphotoreceptor matrix and retinas of Irbp(-/-) mice were increased more than 10-..
  92. ncbi Autophagy is induced by ischemic preconditioning in human livers formerly treated by chemotherapy to limit necrosis
    Davide Degli Esposti
    AP HP, Hopital Paul Brousse, Service de Biochimie et Biologie Moléculaire, Villejuif, France
    Autophagy 6:172-4. 2010
    ..Indeed, necrosis is less frequent (p = 0...
  93. doi High-mobility group box-1 protein and keratin-18, circulating serum proteins informative of acetaminophen-induced necrosis and apoptosis in vivo
    Daniel J Antoine
    MRC Centre for Drug Safety Science, Department of Pharmacology and Therapeutics, University of Liverpool, Sherrington Buildings, Ashton Street, Liverpool L693GE, UK
    Toxicol Sci 112:521-31. 2009
    ..Hepatocyte apoptosis, necrosis, and innate immune activation have been defined as features of the toxicological response associated with the ..
  94. ncbi Effect of bevacizumab on radiation necrosis of the brain
    Javier Gonzalez
    Department of Neuro Oncology, The University of Texas M D Anderson Cancer Center, Houston, TX 77230 1402, USA
    Int J Radiat Oncol Biol Phys 67:323-6. 2007
    Because blocking vascular endothelial growth factor (VEGF) from reaching leaky capillaries is a logical strategy for the treatment of radiation necrosis, we reasoned that bevacizumab might be an effective treatment of radiation necrosis.
  95. pmc Inhibition of caspases increases the sensitivity of L929 cells to necrosis mediated by tumor necrosis factor
    D Vercammen
    Laboratory of Molecular Biology, Flanders Interuniversity Institute for Biotechnology and University of Ghent, B 9000 Ghent, Belgium
    J Exp Med 187:1477-85. 1998
    Murine L929 fibrosarcoma cells treated with tumor necrosis factor (TNF) rapidly die in a necrotic way, due to excessive formation of reactive oxygen intermediates. We investigated the role of caspases in the necrotic cell death pathway...
  96. pmc Activation and caspase-mediated inhibition of PARP: a molecular switch between fibroblast necrosis and apoptosis in death receptor signaling
    Marek Los
    Department of Immunology and Cell Biology, University of Munster, Munster, Germany
    Mol Biol Cell 13:978-88. 2002
    Death ligands not only induce apoptosis but can also trigger necrosis with distinct biochemical and morphological features. We recently showed that in L929 cells CD95 ligation induces apoptosis, whereas TNF elicits necrosis...
  97. ncbi 'Pseudopalisading' necrosis in glioblastoma: a familiar morphologic feature that links vascular pathology, hypoxia, and angiogenesis
    Yuan Rong
    Department of Pathology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30322, USA
    J Neuropathol Exp Neurol 65:529-39. 2006
    ..highly malignant, rapidly progressive astrocytoma that is distinguished pathologically from lower grade tumors by necrosis and microvascular hyperplasia...
  98. ncbi TRAIL induces receptor-interacting protein 1-dependent and caspase-dependent necrosis-like cell death under acidic extracellular conditions
    Olivier Meurette
    Institut National de la Santé et de la Recherche Médicale UMR620, Faculte de Pharmacie, Universite Rennes 1, 2 Avenue du Pr Leon Bernard, 35043 Rennes, France
    Cancer Res 67:218-26. 2007
    Tumor necrosis factor-alpha-related apoptosis-inducing ligand (TRAIL) is a potential anticancer agent that induces apoptosis in cancer cells but not in most normal cells...
  99. ncbi Pathogen-associated molecular pattern recognition rather than development of tissue necrosis contributes to bacterial induction of systemic acquired resistance in Arabidopsis
    Tatiana E Mishina
    Julius von Sachs Institute of Biological Sciences, University of Wurzburg, Julius von Sachs Platz 3, D 97082 Wurzburg, Germany
    Plant J 50:500-13. 2007
    ..syringae inoculation but not the extent of tissue necrosis during these interactions determines the extent of SAR in distant leaves...
  100. pmc Production of hyperpolarized [1,4-13C2]malate from [1,4-13C2]fumarate is a marker of cell necrosis and treatment response in tumors
    Ferdia A Gallagher
    Cancer Research United Kingdom, Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, United Kingdom
    Proc Natl Acad Sci U S A 106:19801-6. 2009
    ..integrity, suggesting that the production of labeled malate from fumarate is a sensitive marker of cellular necrosis. Twenty-four hours after treating implanted lymphoma tumors with etoposide, at which point there were significant ..
  101. doi Necroptosis, a novel form of caspase-independent cell death, contributes to neuronal damage in a retinal ischemia-reperfusion injury model
    Daniel M Rosenbaum
    Department of Neurology, SUNY Downstate Medical Center, Brooklyn, New York, USA
    J Neurosci Res 88:1569-76. 2010
    Necroptosis is programmed necrosis triggered by death receptor signaling. We investigated whether necroptosis contributes to neuronal damage and functional impairment in a model of retinal ischemia.

Research Grants75

  1. NIH Director's Pioneer Award
    Junying Yuan; Fiscal Year: 2009
    ..No Abstract provided ..
  2. Autonomic, Endothelial, and Inflammatory Correlates of Sleep Duration
    MERCEDES RENEE CARNETHON; Fiscal Year: 2012
    ..factor and E-selectin) and adipocytokines that represent insulin resistance (adiponectin, leptin, resistin, tumor necrosis factor-1, plasminogen activator inhibitor-1) and inflammation (C-reactive protein) measured in fasting blood...
  3. A Hybrid PARP Inhibitor and Redox Catalyst for Lung Transplantation
    GARRY JOHN SOUTHAN; Fiscal Year: 2012
    ..depletes its substrate NAD, resulting in an exhaustion of intracellular energetics, ATP depletion, and tissue necrosis. PARP activation also induces a widespread expresion of pro-inflammatory genes that contribute to vascular ..
  4. Ashraf Gorgey; Fiscal Year: 2016
    ..profile, free fatty acids, serum total and free testosterone and IGF-1), and cytokines (c-reactive protein, tumor necrosis factor alpha and IL-6 as inflammatory biomarkers) after 16 weeks of training+Tp and detraining...
  5. A Redox-active PARP Inhibitor for Lung Transplantation
    ANDREW LURIE SALZMAN; Fiscal Year: 2012
    ..of its substrate NAD, which in turn exhausts intracellular energetics, leading to ATP depletion and tissue necrosis. PARP-1 activation also induces a widespread expression of pro-inflammatory genes that contribute to vascular ..
  6. Inhibition of human neutrophil function by Francisella tularensis
    Lee Ann H Allen; Fiscal Year: 2012
    ..Indeed, inhalation of as few as ten organisms is sufficient to cause severe pneumonic disease, tissue necrosis and death...
  7. Hybrid Optical/Doppler Imaging of Ischemia in NEC - a multicenter trial
    David A Benaron; Fiscal Year: 2010
    ..The end result is mucosal injury and/or transmural necrosis of the intestine...
  8. Robert T Means; Fiscal Year: 2014
    ..II acute phase protein, the expression of which is induced by interleukin (IL)-6, and down-regulated by tumor necrosis factor (TNF)...
  9. David A Bernlohr; Fiscal Year: 2014
    ..Initiating this oxidative stress challenge are new findings that describe the tumor necrosis factor 1 (TNF1) dependent down regulation of glutathione S-transferase A4 setting the stage for a molecular ..
  10. A Hybrid Katp Channel Opener to Prevent Radiocontrast-Induced Nephropathy
    Kanneganti Murthy; Fiscal Year: 2012
    ..the elevation in BUN and creatinine, blocked neutrophil inflammation, and prevented histologic evidence of necrosis. Similar benefits have been observed in other rodent redox models, including myocardial ischemia/reperfusion ..
  11. TLR4 Inhibition to Reduce Cerebral Ischemia Reperfusion Injury
    LORI ANN HOLLE; Fiscal Year: 2011
    ..When an artery is occluded, there is an area of tissue that is deprived of oxygen and nutrients, leading to necrosis and infarction...
  12. A Thioredoxin Mimetic for Radiocontrast Nephropathy
    GARRY JOHN SOUTHAN; Fiscal Year: 2012
    ..level of exposure to R-901 will correlate with the extent of tissue protection, as manifested by renal levels of necrosis (histology), lipid peroxidation, neutrophil infiltration, apoptosis, necrosis, peroxynitrite and poly(ADP- ribose)..
  13. DANIEL J CARR; Fiscal Year: 2015
    ..a massive loss of cells residing in the draining lymph node associated with an increase in T cell apoptosis and necrosis. There are also notable changes in recruitment of leukocytes residing in the nervous system post infection of ..
  14. Mechanism-Based Discovery of Protectants Against Iron-Dependant Oxidative Injury
    JUSTIN M SCHWARTZ; Fiscal Year: 2011
    ..species (ROS) after reintroduction of oxygenated blood to ischemic tissue is a major precipitating event causing necrosis and apoptosis in I/R injury...
  15. Iron-Induced Changes in Liver That Predispose to Malignancy
    Harriet C Isom; Fiscal Year: 2010
    ..Histological examination of livers from mice fed a TMHF diet for 9 weeks showed no signs of inflammation or necrosis. Hepatocytes underwent the expected physiological responses to iron in that ferritin levels were increased and ..
  16. SAUL R TZIPORI; Fiscal Year: 2014
    ..low molecular mass GTPases of the Rho family, leading to massive fluid secretion, acute inflammation, and necrosis of the colonic mucosa...
  17. Human Beta-Defensin-1 in HSV-1 Innate Immunity
    LISA KATHLEEN RYAN; Fiscal Year: 2010
    ..In addition to IFN, PDC produce chemokines and tumor necrosis factor-a upon HSV stimulation...
  18. The Role of Decidual Innate Immunity in the Pathogenesis of Preeclampsia
    Se Te Joseph Huang; Fiscal Year: 2012
    ..In leukocyte-free first trimester decidual cells, we found that the pro-inflammatory cytokines, tumor necrosis factor-a (TNF-1) and interleukin-1 beta (IL-12), profoundly enhanced expression of macrophage-colony stimulating ..
  19. Targeting Cell Death to Prevent Ventricular Remodeling and Heart Failure
    Abhinav Diwan; Fiscal Year: 2011
    ..In acute infarction, cardiomyocyte necrosis is inevitable due to oxygen/nutrient deprivation, but is followed by a wave of cell-autonomous death, or ..
  20. Mark S Nanes; Fiscal Year: 2014
    ..We previously showed that tumor necrosis factor-1 (TNF), a major inflammatory mediator in arthritis, potently inhibits OB differentiation, suggesting that ..
  21. Intracellular Serpin Regulation of Intestinal Cell Necrosis
    GARY ARTHUR SILVERMAN; Fiscal Year: 2012
    Intestinal epithelial cell necrosis is a common pathologic feature of many gastrointestinal disorders including inflammatory bowel disease, infectious gastroenteritis and necrotizing enterocolitis...
  22. Mitochondrial Dysfunction and Adipose Insulin Resistance
    DAVID BERNLOHR; Fiscal Year: 2009
    ..Initiating this oxidative stress challenge are new findings that describe the tumor necrosis factor [unreadable] (TNF[unreadable]) dependent down regulation of glutathione S-transferase A4 setting the stage ..
  23. Alcohol, Proteasome Dysfunction in Liver Injury
    Craig J McClain; Fiscal Year: 2013
    ..our VA-supported research and that of others demonstrate a critical role for the proinflammatory cytokine, tumor necrosis factor (TNF), in the development and progression of alcoholic liver disease (ALD)...
  24. Iman Hassan; Fiscal Year: 2014
    ..that show that: 1) TCE exposure of pregnant rats significantly decreased fetal weight and induced focal areas of necrosis within the basal zone of the placenta;and 2) a principal bioactive metabolite of TCE, 1,3-dichlorovinyl cysteine (..
  25. Ted A Bateman; Fiscal Year: 2015
    ..from bone-marrow's early inflammatory response to radiation damage) of osteoclasts via the cytokines tumor necrosis factor-alpha (TNFa) and interleukin-1 (IL-1)...
  26. PEARLIE K BURNETTE; Fiscal Year: 2016
    ..that acute activation in the primary lymphoid system leads to cleavage and shedding of CD62L by the Tumor Necrosis Factor-[unreadable] Converting Enzyme (TACE), which also known as ADAM-17...
  27. LIVER PRESERVATION FOR TRANSPLANTATION
    John J Lemasters; Fiscal Year: 2012
    ..will determine whether mitochondrial dysfunction in liver grafts is due to MPT onset and if dysfunction leads to necrosis and apoptosis;how enhanced ROS formation contributes to MPT onset;and if mitochondrial calcium dysregulation ..
  28. In Vivo Function of TRAF6 As a Target of K63-Linked Polyubiquitination
    DEAN BALLARD; Fiscal Year: 2010
    Signal transduction from cell-surface members of the interleukin-1 receptor/Toll-like receptor (IL-1R/TLR), tumor necrosis factor receptor (TNFR), and immunoglobulin (Ig) superfamilies coordinates the host defense against microbial ..
  29. Treatment of Inflammatory Bowel Disease with Ceramidase Inhibitors
    Lynn W Maines; Fiscal Year: 2012
    ..key mediators of inflammation, and are known to mediate the effects of pro-inflammatory cytokines such as tumor necrosis factor-? (TNF?) that are of central importance in IBD...
  30. Extracellular ubiquitin: role in myocyte apoptosis and myocardial remodeling
    Krishna Singh; Fiscal Year: 2010
    ..neutralizing antibodies against ubiquitin, and other apoptotic agents (angiotensin II, oxidative stress and Tumor necrosis factor-1), and test the hypothesis that secretion of ubiquitin occurs via ?2-AR-dependent signaling pathway...
  31. PARP inhibitor and Redox Catalyst Conjugate for Traumatic Brain Injury
    Kanneganti Murthy; Fiscal Year: 2012
    ..NAD+), thereby depleting ATP stores and provoking energetic failure, loss of cellular homeostasis, neuronal necrosis, and brain infarction...
  32. Effect of Lactobacillus GG on gut permeability and microbiome in VLBW neonates
    ROSE MARIE VISCARDI; Fiscal Year: 2013
    ..across an impaired intestinal mucosal barrier, intense local and systemic inflammatory responses, and intestinal necrosis typical of NEC...
  33. Resuscitation of smoke inhalation and burn injury with a thioredoxin mimetic
    ANDREW LURIE SALZMAN; Fiscal Year: 2012
    ..In severe instances, the ultimate exhaustion of high energy phosphates (ATP) triggers cellular necrosis and the functional loss of the alveolocapillary membrane...
  34. Andrew H Miller; Fiscal Year: 2014
    ..turn have been associated with IFN-alpha-induced increases in peripheral blood and/or CSF concentrations of tumor necrosis factor-alpha and interleukin-6 and their soluble receptors as well as chemokines such as monocyte chemoattractant ..
  35. Effects of GSH +/- Arginine on Markers of Inflammation Among Adults with CVD Risk
    Christopher D Gardner; Fiscal Year: 2010
    ..serum markers of inflammation including monocyte chemoattractant protein-1 (MCP-1), interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-1) and soluble intercellular adhesion molecule-1 (sICAM-1)...
  36. Arnold Louie; Fiscal Year: 2014
    ..By quantifying the amount of drug inside hPRTE cells over time and observing for apoptosis or necrosis, we can derive a relationship between drug exposure, duration and nephrotoxic event occurrence...
  37. William M Pandak; Fiscal Year: 2016
    ..A fraction of patients with NAFLD progress to liver cell necrosis, inflammation, and progressive fibrosis. NAFLD is a now recognized as a leading cause of cirrhosis in the U.S...
  38. Mindfulness Based Stress Reduction as an Adjunctive Treatment for Psoriasis
    Jan A Moynihan; Fiscal Year: 2013
    ..production of many of the proinflammatory cytokines involved in psoriasis, including interleukin (IL)-6 and tumor necrosis factor (TNF)-1...
  39. Melinda Sheffield-Moore; Fiscal Year: 2014
    ..Breakdown is affected because catabolic factors such as tumor necrosis factor-? (TNF-?) enhance nuclear factor-?B (NF-?B), which in turn activates muscle proteolysis via the ubiquitin-..
  40. Elizabeth R Jacobs; Fiscal Year: 2016
    ..1) To use SPECT and nuclear medicine probes which target apoptosis/necrosis or oxidoreductive state to detect unilateral IR lung injury in vivo We will correlate serial SPECT data after IR ..
  41. Karen H Costenbader; Fiscal Year: 2014
    ..and analyzed for changes in biomarkers of systemic inflammation: C-reactive protein, interleukin-6, and tumor necrosis factor-a...
  42. Zhongcong Xie; Fiscal Year: 2016
    ..Neuroinflammation includes microglia activation and increases in pro-inflammatory cytokines such as tumor necrosis factor (TNF)-[unreadable], interleukin-6 (IL-6), and IL-1[unreadable] in the brain...
  43. Alexandra M Machikas; Fiscal Year: 2014
    ..In this regard, mitochondria have been targeted as mediators of apoptosis, autophagy and necrosis. An emerging concept also includes a key role for programmed necrosis (PN) in the regulation of cell death via ..
  44. Novel Therapeutic Targets in Necrotizing Enterocolitis
    Peter J Giannone; Fiscal Year: 2012
    ..Indications for surgical intervention include bowel perforation and/or signs of bowel necrosis. Infants with NEC who require surgical intervention are at high risk for poor neurodevelopmental and functional ..
  45. Calorie Restriction &Body Composition, Function, &QoL in Older Adults
    Julie L Locher; Fiscal Year: 2013
    ..Specific Aim #2: blood pressure, blood glucose, insulin, lipids, C-reactive protein, adiponectin, leptin, tumor necrosis factor-1, interleukin-6), functional status, and quality of life (Specific Aim #3: life space mobility, Short ..
  46. A Prospective Study of Adiposity and Subclinical Coronary Artery Disease
    CHRISTINA LYNN WASSEL; Fiscal Year: 2010
    ..We will test for associations between these measures and four inflammatory adipocytokines (interleukin-6, tumor necrosis factor - 1, leptin, adiponectin), CVD risk factors, and CAC...
  47. Control of Drug Delivery to the CNS: Modulating P-glycoprotein Activity
    William A Banks; Fiscal Year: 2013
    ..only;minimum three) Drug, blood-brain barrier, Brain, CNS, p-glycoprotein, innate immune system, cytokines, tumor necrosis factor-alpha, nitric oxide BRIEF STATEMENT OF RESEARCH OBJECTIVES (Do not use continuation sheets) A major ..
  48. JULIE MARIE VOSE; Fiscal Year: 2016
    ..endothelial growth factor (VEGF), soluble Interleukin-2 receptor (slL2r), lnterleukein-12 (ILI 2), and tumor necrosis factor alpha (TNFa) in the post transplant period and correlate the results with the event-free survival (EFS) ..
  49. C Yan Cheng; Fiscal Year: 2016
    ..Recent studies have shown that cytokines (e.g., tumor necrosis factor ?, TNF?, and transforming growth factor-?2/-3, TGF-?2 or -?3) have a disruptive effect on BTB integrity, ..
  50. Edward O McFalls; Fiscal Year: 2016
    ..to continuing or repetitive myocardial ischemia and is characterized by hypoperfusion without evidence of necrosis. Our group has successfully established a reproducible swine model of hibernating myocardium and has studied this ..
  51. Edward A Neuwelt; Fiscal Year: 2015
    ..permeability will correlate with drug delivery while blood volume will correlate with inflammation, hypoxia, and necrosis in individual metastases...
  52. Beth A McCormick; Fiscal Year: 2016
    ..by a pronounced infiltration of neutrophils (PMNs) into colonic mucosal lesions, accompanied by epithelial cell necrosis and ulceration...
  53. Jinah Choi; Fiscal Year: 2015
    ..Toll-like receptor 4 (TLR4) and tumor necrosis factor alpha (TNF?) are elevated in hepatitis C patients...
  54. Cyclic AMP, Cytokine Modulation and Alcoholic Liver Disease
    Craig J McClain; Fiscal Year: 2013
    ..Abnormal cytokine metabolism is a major feature of ALD. Elevated serum concentrations of tumor necrosis factor (TNF) and TNF-inducible proinflammatory cytokines/chemokines, such as IL-8 and IL-18 have been reported in ..
  55. Steven L Gonias; Fiscal Year: 2014
    ..by controlling cell-surface levels of other receptors, including the urokinase receptor (uPAR) and tumor necrosis factor receptor-1 (TNFR1)...
  56. Caveolins in the Pathogenesis of Idiopathic Pulmonary Fibrosis
    Dan N Predescu; Fiscal Year: 2010
    ..intraalveolar environment that facilitate an increased fibrotic response, and cytokines such as tumor necrosis factor and transforming factor ? (TGF?)...
  57. Jac A Nickoloff; Fiscal Year: 2016
    ..including cell survival, genome stability, and cell death/permanent growth arrest via apoptosis, autophagy, necrosis, senescence, or mitotic catastrophe...
  58. Adhesion of Leptospira interrogans to Human Cell Surface Receptors
    Jenifer L Coburn; Fiscal Year: 2010
    ..These changes lead to increased permeability of the endothelial layers to the pathogen, without evidence of necrosis or apoptosis...
  59. DAVID ANTONETTI; Fiscal Year: 2016
    ..of growth factors such as vascular endothelial growth factor (VEGF) and inflammatory cytokines such as tumor necrosis factor (TNF)...
  60. Synergistic Roles of Adiponectin & PPARgamma in Beta-Cell Survival/Proliferation
    William L Holland; Fiscal Year: 2010
    ..Moreover, the susceptibility of beta cells to both apoptosis and necrosis during isolation or transplantation has hindered attempts to utilize islet transplantation as a treatment for ..
  61. Georgios I Papachristou; Fiscal Year: 2014
    ..serum at admission (primary end-point) and at 24 and 48 hours from admission to measure the 5 biomarkers (tumor necrosis factor-a receptor-1, interleukin-8, hepatocyte growth factor, angiopoietin-2, resistin) using Luminex technology...
  62. HIFU-enhanced tumor vaccines
    Chandan Guha; Fiscal Year: 2012
    ..Previous experience with High Intensity Focused Ultrasound (HIFU) has demonstrated that HIFU induces coagulative necrosis in tumor tissues and controls tumor growth of localized prostate, renal cell and liver cancers...
  63. Therapeutic Potential of PARP inhibitor for Acute Pancreatitis
    Latha Paka; Fiscal Year: 2010
    ..Its pathogenesis remains obscure and is involved in a process of acute inflammation and necrosis in the pancreas, with variable involvement of regional tissues or organ systems that leads to a systemic ..
  64. Role of ATM in Cardiac Myocyte Loss and Myocardial Remodeling
    Krishna Singh; Fiscal Year: 2009
    ..Evidence has been provided that inhibition of ATM induces a switch from apoptosis to necrosis in murine embryonic fibroblasts...
  65. Cytoprotective cytokine signaling and reperfusion injury
    DOUGLAS LOWELL MANN; Fiscal Year: 2010
    ..Studies from this laboratory have shown that the cytoprotective effects of tumor necrosis factor (TNF) are conveyed by both the type 1 (TNFR1) and type 2 (TNFR2) TNF receptors...
  66. Inflammation and Infection as Risk Factors in Stroke
    Mitchell Elkind; Fiscal Year: 2006
    ..pneumoniae) is associated with stroke risk, and that elevated white blood cell count and soluble tumor necrosis factor receptor levels are associated with carotid atherosclerosis...
  67. Bisphosphonate-related osteonecrosis of the jaw: Bridging the clinical-preclinica
    Matthew R Allen; Fiscal Year: 2010
    ..We hypothesize these regions of bone matrix necrosis within the mandible, which are clearly void of viable osteocytes and have disrupted canalicular networks, ..
  68. INTERSTITIAL NEUTRON THERAPY FOR GLIOBLASTOMA
    ALFRED YOUNG; Fiscal Year: 1991
    ..beam neutron therapy has shown that neutrons can completely eradicate GBM but that unacceptable radiation necrosis of normal brain frequently follows...
  69. ANESTHETIC TOXICITY--MECHANISMS AND PREVENTION
    Evan Kharasch; Fiscal Year: 1999
    ..Halothane, the most widely used anesthetic in the world, causes a rare but fatal fulminant hepatic necrosis. Moreover, it commonly causes altered postoperative mixed function oxidase activity...
  70. OVARIAN TUMOR NECROSIS FACTOR
    Paul Terranova; Fiscal Year: 2004
    The objective of this application is to delineate the mechanisms by which tumor necrosis factor alpha (TNF) and in receptor system inhibit gonadotropin-stimulated ovarian granulosa cell estradiol secretion using a mouse model...
  71. PRECONDITIONING: PMN ADHESION AND MICROVASCULAR INJURY
    RONALD KORTHUIS; Fiscal Year: 2003
    ..tissue injury are not clear, preliminary data from our laboratory indicates that delayed IPC prevents muscle necrosis induced by IR by inhibiting leukocyte adherence and emigration during reperfusion after the second ischemic ..
  72. FUNCTIONS OF ENDOTHELIAL CELL FACTOR IX BINDING PROTEIN
    David Stern; Fiscal Year: 1992
    ..One endothelial cell procoagulant cofactor whose expression is enhanced by tumor necrosis factor (TNF) is a cell surface binding site for Factors IX and IXa, which in the presence of Factors VIII and X ..
  73. PATHOGENESIS AND PATHOPHYSIOLOGY OF BACTERIAL MENINGITIS
    WILLIAM SCHELD; Fiscal Year: 1991
    ..g. E. coli, H, influenzae) and host factors (e.g. leukocytes, interleukin-1, tumor necrosis factor) on the traversal of 1125 I-albumin across the BBB in vivo and in vitro...
  74. HUMAN LYMPHOCYTE PRODUCTION OF TUMOR NECROSIS FACTOR
    Sun Sang Sung; Fiscal Year: 1993
    Tumor necrosis factor (TNF) is important in inducing a number of abnormal physiological conditions such as shock and cachexia...