cytochromes c

Summary

Summary: Cytochromes of the c type that are found in eukaryotic MITOCHONDRIA. They serve as redox intermediates that accept electrons from MITOCHONDRIAL ELECTRON TRANSPORT COMPLEX III and transfer them to MITOCHONDRIAL ELECTRON TRANSPORT COMPLEX IV.

Top Publications

  1. ncbi Direct activation of Bax by p53 mediates mitochondrial membrane permeabilization and apoptosis
    Jerry E Chipuk
    Division of Cellular Immunology, La Jolla Institute for Allergy and Immunology, 10355 Science Center Drive, San Diego, CA 92121, USA
    Science 303:1010-4. 2004
  2. pmc BID, BIM, and PUMA are essential for activation of the BAX- and BAK-dependent cell death program
    Decheng Ren
    Molecular Oncology, Department of Medicine, Washington University School of Medicine, St Louis, MO 63110, USA
    Science 330:1390-3. 2010
  3. ncbi Mitochondria, oxidative stress and cell death
    Martin Ott
    Institute of Environmental Medicine, Karolinska Institutet, S 171 77 Stockholm, Sweden
    Apoptosis 12:913-22. 2007
  4. ncbi Prevention of apoptosis by Bcl-2: release of cytochrome c from mitochondria blocked
    J Yang
    Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA
    Science 275:1129-32. 1997
  5. pmc A unified model of mammalian BCL-2 protein family interactions at the mitochondria
    Fabien Llambi
    Department of Immunology, St Jude Children s Research Hospital, Memphis, TN 38105, USA
    Mol Cell 44:517-31. 2011
  6. ncbi Mechanisms of cytochrome c release from mitochondria
    C Garrido
    INSERM U517, Faculty of Medicine and Pharmacy, F 21033 Dijon, France
    Cell Death Differ 13:1423-33. 2006
  7. ncbi Mitochondrial p53 activates Bak and causes disruption of a Bak-Mcl1 complex
    J I Ju Leu
    Department of Genetics, University of Pennsylvania School of Medicine, 422 Curie Boulevard, Philadelphia, PA 19104, USA
    Nat Cell Biol 6:443-50. 2004
  8. ncbi Cytochrome C-mediated apoptosis
    Xuejun Jiang
    Cell Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Annu Rev Biochem 73:87-106. 2004
  9. ncbi The mitochondrial death pathway and cardiac myocyte apoptosis
    Michael T Crow
    Department of Medicine, Johns Hopkins University School of Medicine, 5501 Hopkins Bayview Circle, Rm 5A 58, Baltimore, MD 21224, USA
    Circ Res 95:957-70. 2004
  10. ncbi Cytochrome c acts as a cardiolipin oxygenase required for release of proapoptotic factors
    Valerian E Kagan
    Center for Free Radical and Antioxidant Health and Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA
    Nat Chem Biol 1:223-32. 2005

Detail Information

Publications309 found, 100 shown here

  1. ncbi Direct activation of Bax by p53 mediates mitochondrial membrane permeabilization and apoptosis
    Jerry E Chipuk
    Division of Cellular Immunology, La Jolla Institute for Allergy and Immunology, 10355 Science Center Drive, San Diego, CA 92121, USA
    Science 303:1010-4. 2004
    ..We propose that when p53 accumulates in the cytosol, it can function analogously to the BH3-only subset of proapoptotic Bcl-2 proteins to activate Bax and trigger apoptosis...
  2. pmc BID, BIM, and PUMA are essential for activation of the BAX- and BAK-dependent cell death program
    Decheng Ren
    Molecular Oncology, Department of Medicine, Washington University School of Medicine, St Louis, MO 63110, USA
    Science 330:1390-3. 2010
    ..Thus, many forms of apoptosis require direct activation of BAX and BAK at the mitochondria by a member of the BID, BIM, or PUMA family of proteins...
  3. ncbi Mitochondria, oxidative stress and cell death
    Martin Ott
    Institute of Environmental Medicine, Karolinska Institutet, S 171 77 Stockholm, Sweden
    Apoptosis 12:913-22. 2007
    ..Conversely, mitochondrial antioxidant enzymes protect from apoptosis. Hence, there is accumulating evidence supporting a direct link between mitochondria, oxidative stress and cell death...
  4. ncbi Prevention of apoptosis by Bcl-2: release of cytochrome c from mitochondria blocked
    J Yang
    Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA
    Science 275:1129-32. 1997
    ..Overexpression of Bcl-2 prevented the efflux of cytochrome c from the mitochondria and the initiation of apoptosis. Thus, one possible role of Bcl-2 in prevention of apoptosis is to block cytochrome c release from mitochondria...
  5. pmc A unified model of mammalian BCL-2 protein family interactions at the mitochondria
    Fabien Llambi
    Department of Immunology, St Jude Children s Research Hospital, Memphis, TN 38105, USA
    Mol Cell 44:517-31. 2011
    ..Further, MODE 2 sequestration prevents mitochondrial fusion. We provide a unified model of BCL-2 family function that helps to explain otherwise paradoxical observations relating to MOMP, apoptosis, and mitochondrial dynamics...
  6. ncbi Mechanisms of cytochrome c release from mitochondria
    C Garrido
    INSERM U517, Faculty of Medicine and Pharmacy, F 21033 Dijon, France
    Cell Death Differ 13:1423-33. 2006
    ..This review deals with the events involved in Cyt c release from mitochondria, with special attention to its regulation and final consequences...
  7. ncbi Mitochondrial p53 activates Bak and causes disruption of a Bak-Mcl1 complex
    J I Ju Leu
    Department of Genetics, University of Pennsylvania School of Medicine, 422 Curie Boulevard, Philadelphia, PA 19104, USA
    Nat Cell Biol 6:443-50. 2004
    ..These results are consistent with a model in which p53 and Mcl1 have opposing effects on mitochondrial apoptosis by interacting with, and modulating the activity of, the death effector Bak...
  8. ncbi Cytochrome C-mediated apoptosis
    Xuejun Jiang
    Cell Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Annu Rev Biochem 73:87-106. 2004
    ..In this review, we focus on the recent progress in understanding the biochemical mechanisms and regulation of the pathway, the roles of the pathway in physiology and disease, and their potential therapeutic values...
  9. ncbi The mitochondrial death pathway and cardiac myocyte apoptosis
    Michael T Crow
    Department of Medicine, Johns Hopkins University School of Medicine, 5501 Hopkins Bayview Circle, Rm 5A 58, Baltimore, MD 21224, USA
    Circ Res 95:957-70. 2004
    ..Each of these pathways has been implicated in myocardial pathology. In this review, we summarize recent advances in the understanding of the intrinsic pathway and how it relates to cardiac myocyte death and heart disease...
  10. ncbi Cytochrome c acts as a cardiolipin oxygenase required for release of proapoptotic factors
    Valerian E Kagan
    Center for Free Radical and Antioxidant Health and Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA
    Nat Chem Biol 1:223-32. 2005
    ..These results provide insight into the role of reactive oxygen species in triggering the cell-death pathway and describe an early role for cytochrome c before caspase activation...
  11. ncbi Hexokinase-mitochondria interaction mediated by Akt is required to inhibit apoptosis in the presence or absence of Bax and Bak
    Nathan Majewski
    Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, Illinois 60607, USA
    Mol Cell 16:819-30. 2004
    ....
  12. ncbi Fucoidan induces apoptosis through activation of caspase-8 on human breast cancer MCF-7 cells
    Yumi Yamasaki-Miyamoto
    Laboratory of Food Chemistry, Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, 6 10 1 Hakozaki, Higashi ku, Fukuoka 812 8581, Japan
    J Agric Food Chem 57:8677-82. 2009
    ..However, caspase-9-specific inhibitor exerted a moderate inhibitory effect on the cytotoxicity of fucoidan. These data indicated that fucoidan could induce apoptotic cell death through a caspase-8-dependent pathway in MCF-7 cells...
  13. ncbi Cytochrome c: functions beyond respiration
    Yong Ling P Ow
    The Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, Toronto, Ontario M5G 2C1, Canada
    Nat Rev Mol Cell Biol 9:532-42. 2008
    ..As well as its role in canonical intrinsic apoptosis, cytochrome c amplifies signals that are generated by other apoptotic pathways and participates in certain non-apoptotic functions...
  14. ncbi Overlapping cleavage motif selectivity of caspases: implications for analysis of apoptotic pathways
    G P McStay
    Department of Immunology, St Jude Children s Research Hospital, 332 North Lauderdale Street, Memphis, TN 38105, USA
    Cell Death Differ 15:322-31. 2008
    ..Finally, caspase activity in cells lacking caspase-9 displayed substrate cleavage activity of a putative caspase-9-specific substrate underlining the lack of selectivity of peptide-based substrates and inhibitors of caspases...
  15. pmc Endoplasmic reticulum BIK initiates DRP1-regulated remodelling of mitochondrial cristae during apoptosis
    Marc Germain
    Department of Biochemistry, McGill University, Montreal, QC, Canada
    EMBO J 24:1546-56. 2005
    ..When expressed together, BIK and NOXA cause rapid release of mobilized cytochrome c and activation of caspases...
  16. ncbi Mitochondrial regulation of insect cell apoptosis: evidence for permeability transition pore-independent cytochrome-c release in the Lepidopteran Sf9 cells
    Regalla Kumarswamy
    Natural Radiation Response Mechanisms Group, Division of Radiation Biosciences, Institute of Nuclear Medicine and Allied Sciences, Brig SK Mazumdar Road, Delhi 110054, India
    Int J Biochem Cell Biol 41:1430-40. 2009
    ....
  17. ncbi GAPDH and autophagy preserve survival after apoptotic cytochrome c release in the absence of caspase activation
    Anna Colell
    Department of Cell Death and Proliferation, Institut d Investigacions Biomediques de Barcelona IIBB CSIC, IDIBAPS, 08036 Barcelona, Spain
    Cell 129:983-97. 2007
    ..Therefore, GAPDH mediates an elevation in glycolysis and enhanced autophagy that cooperate to protect cells from CICD...
  18. ncbi p73 Induces apoptosis via PUMA transactivation and Bax mitochondrial translocation
    Gerry Melino
    Biochemistry Laboratory, Instituto Dermopatico Dell Immacolata Istituto di Ricovero e Cura a Carattere Scientifico, Department of Experimental Medicine and Biochemical Sciences, University of Rome Tor Vergata, 00133 Rome, Italy
    J Biol Chem 279:8076-83. 2004
    ..Our findings demonstrate that p73 elicits apoptosis via the mitochondrial pathway using PUMA and Bax as mediators...
  19. ncbi Calcium orchestrates apoptosis
    Mark P Mattson
    Nat Cell Biol 5:1041-3. 2003
  20. pmc The multiple functions of cytochrome c and their regulation in life and death decisions of the mammalian cell: From respiration to apoptosis
    Maik Huttemann
    Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI 48201, USA
    Mitochondrion 11:369-81. 2011
    ..Cytc regulation in respiration and cell death is discussed in a human disease context including neurodegenerative and cardiovascular diseases, cancer, and sepsis...
  21. ncbi BH3 domains of BH3-only proteins differentially regulate Bax-mediated mitochondrial membrane permeabilization both directly and indirectly
    Tomomi Kuwana
    La Jolla Institute for Allergy and Immunology, 10355 Science Center Drive, San Diego, CA 92121, USA
    Mol Cell 17:525-35. 2005
    ..In this model, the simple inhibition of antiapoptotic functions is insufficient to induce apoptosis unless a direct activator of Bax or Bak is present...
  22. ncbi Bax channel inhibitors prevent mitochondrion-mediated apoptosis and protect neurons in a model of global brain ischemia
    Claudio Hetz
    Serono Pharmaceutical Research Institute, 14 Chemin des Aulx, CH 1228 Plan les Ouates, Geneva, Switzerland
    J Biol Chem 280:42960-70. 2005
    ..The protective effect in the animal model correlated with decreased cytochrome c release in the infarcted area. This is the first demonstration that Bax channel activity is required in apoptosis...
  23. pmc Opa1-mediated cristae opening is Bax/Bak and BH3 dependent, required for apoptosis, and independent of Bak oligomerization
    Ryuji Yamaguchi
    La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA
    Mol Cell 31:557-69. 2008
    ..Thus, apoptosis requires a subtle form of Opa1-dependent crista remodeling that is induced by BH3-only proteins and Bax/Bak but independent of MOMP...
  24. pmc Developmental shift of cyclophilin D contribution to hypoxic-ischemic brain injury
    Xiaoyang Wang
    Perinatal Center, University of Gothenburg, SE 405 30 Gothenburg, Sweden
    J Neurosci 29:2588-96. 2009
    ..The role of CypD in HI shifts from a predominantly prosurvival protein in the immature to a cell death mediator in the adult brain...
  25. pmc Analysis of the composition, assembly kinetics and activity of native Apaf-1 apoptosomes
    Michelle M Hill
    Molecular Cell Biology Laboratory, Department of Genetics, The Smurfit Institute, Trinity College, Dublin, Ireland
    EMBO J 23:2134-45. 2004
    ..Surprisingly, PHAPI also enhanced the activity of purified caspase-3, suggesting that it may act as a co-factor for this protease...
  26. pmc The MCL-1 BH3 helix is an exclusive MCL-1 inhibitor and apoptosis sensitizer
    Michelle L Stewart
    Department of Pediatric Oncology, Dana Farber Cancer Institute and Children s Hospital Boston, Harvard Medical School, Boston, Massachusetts, USA
    Nat Chem Biol 6:595-601. 2010
    ..By leveraging nature's solution to ligand selectivity, we generated an MCL-1-specific agent that defines the structural and functional features of targeted MCL-1 inhibition...
  27. ncbi Hierarchical regulation of mitochondrion-dependent apoptosis by BCL-2 subfamilies
    Hyungjin Kim
    Molecular Oncology, Department of Medicine, Washington University School of Medicine, St Louis, MO 63110, USA
    Nat Cell Biol 8:1348-58. 2006
    ..Our data establish a hierarchical regulation of mitochondrion-dependent apoptosis by various BCL-2 subfamilies...
  28. ncbi The influence of age on apoptotic and other mechanisms of cell death after cerebral hypoxia-ischemia
    C Zhu
    Department of Physiology, Goteborg University, Goteborg, Sweden
    Cell Death Differ 12:162-76. 2005
    ..To our knowledge, this is the first report demonstrating developmental regulation of AIF-mediated cell death as well as involvement of autophagy in a model of brain injury...
  29. pmc Mitochondrial fission and cristae disruption increase the response of cell models of Huntington's disease to apoptotic stimuli
    Veronica Costa
    Department of Cell Physiology and Medicine, University of Geneva, Geneva, Switzerland
    EMBO Mol Med 2:490-503. 2010
    ..Conversely, the increased apoptosis can be corrected by manoeuvres that prevent fission and cristae remodelling. In conclusion, the cristae remodelling of the fragmented HD mitochondria contributes to their hypersensitivity to apoptosis...
  30. pmc Cytochrome c/cardiolipin relations in mitochondria: a kiss of death
    Valerian E Kagan
    Center for Free Radical and Antioxidant Health, Pittsburgh, PA 15219, USA
    Free Radic Biol Med 46:1439-53. 2009
    ..Finally, new concepts in drug discovery based on the design of mitochondria-targeted inhibitors of cyt c/CL peroxidase and CL peroxidation with antiapoptotic effects are presented...
  31. pmc Caspases 3 and 7: key mediators of mitochondrial events of apoptosis
    Saquib A Lakhani
    Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA
    Science 311:847-51. 2006
    ..Furthermore, the early apoptotic events of Bax translocation and cytochrome c release were also delayed. We conclude that caspases 3 and 7 are critical mediators of mitochondrial events of apoptosis...
  32. ncbi Specific ablation of the apoptotic functions of cytochrome C reveals a differential requirement for cytochrome C and Apaf-1 in apoptosis
    Zhenyue Hao
    The Campbell Family Institute for Breast Cancer Research, University Health Network, University of Toronto, Toronto, Ontario M5G 2C1, Canada
    Cell 121:579-91. 2005
    ..These studies indicate the existence of a Cyt c- and apoptosome-independent but Apaf-1-dependent mechanism(s) for caspase activation...
  33. ncbi Protein phosphatase 2A regulates apoptosis in intestinal epithelial cells
    Ramesh M Ray
    Department of Physiology, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA
    J Biol Chem 280:31091-100. 2005
    ....
  34. pmc Prohibitin (PHB) acts as a potent survival factor against ceramide induced apoptosis in rat granulosa cells
    Indrajit Chowdhury
    Department of Obstetrics and Gynecology, Morehouse School of Medicine, Atlanta, GA, USA
    Life Sci 89:295-303. 2011
    ..Our previous studies have shown that Prohibitin (PHB) is intimately involved in GCs differentiation, atresia, and luteolysis...
  35. ncbi Apoptogenic activity of 2α,3α-dihydroxyurs-12-ene-28-oic acid from Prunella vulgaris var. lilacina is mediated via mitochondria-dependent activation of caspase cascade regulated by Bcl-2 in human acute leukemia Jurkat T cells
    Hyun Ju Woo
    Laboratory of Immunobiology, School of Life Science and Biotechnology, College of Natural Sciences, Kyungpook National University, Daegu, Republic of Korea
    J Ethnopharmacol 135:626-35. 2011
    ..The present study evaluated the apoptotic effect of 2α,3α-dihydroxyurs-12-en-28-oic acid (DHURS), purified from the dried spikes on human acute leukemia Jurkat T cells...
  36. pmc The cytochrome c maturation components CcmF, CcmH, and CcmI form a membrane-integral multisubunit heme ligation complex
    Carsten Sanders
    Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 283:29715-22. 2008
    ..The findings are discussed with respect to defining the obligatory components of a minimalistic heme-apocytochrome c ligation complex in R. capsulatus...
  37. ncbi Curcumin suppresses constitutive activation of nuclear factor-kappa B and requires functional Bax to induce apoptosis in Burkitt's lymphoma cell lines
    Azhar R Hussain
    Department of Human Cancer Genomic Research, King Fahad National Center for Children s Cancer and Research, King Faisal Specialist Hospital and Research Center, MBC 98 16, P O Box 3354, Riyadh 11211, Saudi Arabia
    Mol Cancer Ther 7:3318-29. 2008
    ..These findings also raise the possibility that incorporation of curcumin in treatment regimens may provide a novel approach for the treatment of Burkitt's lymphomas and provide the molecular basis for such future translational efforts...
  38. pmc Peroxidase activity and structural transitions of cytochrome c bound to cardiolipin-containing membranes
    Natalia A Belikova
    Center for Free Radical and Antioxidant Health and Department of Environmental and Occupational Health, University of Pittsburgh, 100 Technology Drive, Suite 350, Pittsburgh, Pennsylvania 15219 3130, USA
    Biochemistry 45:4998-5009. 2006
    ....
  39. pmc Hexokinase II detachment from the mitochondria potentiates cisplatin induced cytotoxicity through a caspase-2 dependent mechanism
    Nataly Shulga
    Department of Molecular Biology, School of Osteopathic Medicine, University of Medicine and Dentistry of New Jersey, Stratford, NJ, USA
    Cell Cycle 8:3355-64. 2009
    ..Notably, the detachment of hexokinase II from the mitochondria markedly potentiates the onset of caspase-2 induced mitochondrial damage, thus resulting in a synergistic induction of cisplatin induced cytotoxicity...
  40. pmc Involvement of mitochondrial pathway in NCTD-induced cytotoxicity in human hepG2 cells
    Cheng Chang
    Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China
    J Exp Clin Cancer Res 29:145. 2010
    ..However, the detailed mechanisms underlying this process are generally unclear. The aim of this study was to investigate the mechanism of NCTD-induced apoptosis in HepG2 cells...
  41. ncbi Antiapoptotic effects of GLP-1 in murine HL-1 cardiomyocytes
    Susana Ravassa
    Division of Cardiovascular Sciences, Center for Applied Medical Research, University Clinic, School of Medicine, University of Navarra, Pamplona, Spain
    Am J Physiol Heart Circ Physiol 300:H1361-72. 2011
    ..This cytoprotective ability is mediated mainly by the PI3K pathway and partially by the ERK1/2 pathway and seems to be glucose independent. It is proposed that therapies based on GLP-1 may contribute to prevent cardiomyocyte apoptosis...
  42. ncbi Mitochondrial signaling pathway is also involved in bisphenol A induced germ cell apoptosis in testes
    Qun Wang
    Department of Toxicology, Anhui Medical University, Hefei, China
    Toxicol Lett 199:129-35. 2010
    ..Taken together, these results suggest that pubertal BPA exposure induces germ cell apoptosis in testes through not only the Fas/FasL signaling pathway but also the mitochondrial apoptotic pathway...
  43. ncbi Human alphaA- and alphaB-crystallins bind to Bax and Bcl-X(S) to sequester their translocation during staurosporine-induced apoptosis
    Y W Mao
    Department of Molecular Biology, University of Medicine and Dentistry of New Jersey, Stratford, NJ, USA
    Cell Death Differ 11:512-26. 2004
    ..Thus, our results demonstrate a novel antiapoptotic mechanism for alpha-crystallins...
  44. ncbi Indirubin-3'-oxime prevents hepatic I/R damage by inhibiting GSK-3beta and mitochondrial permeability transition
    Ana T Varela
    Center for Neurosciences and Cell Biology, Department of Zoology, University of Coimbra, 3004 517 Coimbra, Portugal
    Mitochondrion 10:456-63. 2010
    ..Pre-treatment with indirubin-3'-oxime in conditions of hepatic I/R, protects the liver by maintaining mitochondrial function and hepatic energetic balance...
  45. pmc Flurbiprofen, a cyclooxygenase inhibitor, protects mice from hepatic ischemia/reperfusion injury by inhibiting GSK-3β signaling and mitochondrial permeability transition
    Hailong Fu
    Departments of Anesthesiology, Changzheng Hospital, Second Military Medical University, Shanghai, China
    Mol Med 18:1128-35. 2012
    ....
  46. ncbi Enzymatic activity and thermal stability of metallo proteins in hydrated ionic liquids
    Kyoko Fujita
    Department of Biotechnology, Tokyo University of Agriculture and Technology, Koganei, Tokyo184 8588, Japan
    Biopolymers 93:1093-9. 2010
    ..These proteins retained the surroundings of the active site after dissolution in Hy[ch][dhp]. Some metallo proteins were found to retain their activity in the Hy[ch][dhp]...
  47. ncbi Distinct mechanisms of cardiomyocyte apoptosis induced by doxorubicin and hypoxia converge on mitochondria and are inhibited by Bcl-xL
    Janice L V Reeve
    Department of Biochemistry, National Centre for Biomedical Engineering Science, National University of Ireland, Galway, Ireland
    J Cell Mol Med 11:509-20. 2007
    ..These data demonstrate that two distinct cardiomyocyte-damaging stimuli converge on mitochondria thus presenting this organelle as a potentially important therapeutic target for anti-apoptotic strategies for cardiovascular diseases...
  48. ncbi Mitochondrial disruption in Drosophila apoptosis
    Eltyeb Abdelwahid
    Cutaneous Biology Research Center, Massachusetts General Hospital Harvard Medical School, Building 149, 13th Street, Charlestown, MA 02129, USA
    Dev Cell 12:793-806. 2007
    ..Significantly, we show that inhibition of Reaper or Hid mitochondrial localization or inhibition of Drp1 significantly inhibits apoptosis, indicating a role for mitochondrial disruption in fly apoptosis...
  49. pmc Newcastle disease virus exerts oncolysis by both intrinsic and extrinsic caspase-dependent pathways of cell death
    Subbiah Elankumaran
    Virginia Maryland Regional College of Veterinary Medicine, University of Maryland, College Park, MD 20742, USA
    J Virol 80:7522-34. 2006
    ..We have also shown that trackable oncolytic NDV could be developed without any reduction in oncolytic efficacy...
  50. ncbi Ischemic postconditioning protects against global cerebral ischemia/reperfusion-induced injury in rats
    Jing Ye Wang
    Department of Neurology, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
    Stroke 39:983-90. 2008
    ..In this study, we tested the hypothesis that ischemic postconditioning reduces global cerebral ischemia/reperfusion-induced structural and functional injury in rats...
  51. pmc A potent lead induces apoptosis in pancreatic cancer cells
    Zuojia Liu
    State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, China
    PLoS ONE 7:e37841. 2012
    ..From this perspective, NSC48693 should help to open up a new opportunity for the treatment of patients with pancreatic cancer...
  52. ncbi Cardiolipin drives cytochrome c proapoptotic and antiapoptotic actions
    Paolo Ascenzi
    Interdepartmental Laboratory for Electron Microscopy, Via della Vasca Navale 79, Roma, Italy
    IUBMB Life 63:160-5. 2011
    ..e., inhibiting lipid peroxidation and hhcytc traslocation). Here, the CL-driven allosteric modulation of hhcytc properties is reviewed, highlighting proapoptotic and antiapoptotic actions..
  53. pmc Targeting neonatal ischemic brain injury with a pentapeptide-based irreversible caspase inhibitor
    D Chauvier
    Theraptosis Research Laboratory, THERAPTOSIS SA, Pasteur Biotop, Institut Pasteur, Paris 75015, France
    Cell Death Dis 2:e203. 2011
    ..Safety pharmacology investigations, and toxicology studies in rodent and canine neonates, suggest that TRP601 is a lead compound for further drug development to treat ischemic brain damage in human newborns...
  54. ncbi Mulberry fruit (Moris fructus) extracts induce human glioma cell death in vitro through ROS-dependent mitochondrial pathway and inhibits glioma tumor growth in vivo
    Ji Cheon Jeong
    Dongguk University, Kyung Ju, Korea
    Nutr Cancer 62:402-12. 2010
    ..These findings suggest that MF extracts result in human glioma cell death in vitro through ROS-dependent mitochondrial pathway and glioma tumor growth in vivo via reduction of tumor cell proliferation and induction of apoptosis...
  55. pmc VDAC regulation: role of cytosolic proteins and mitochondrial lipids
    Tatiana K Rostovtseva
    Laboratory of Physical and Structural Biology, Program in Physical Biology, NICHD, National Institutes of Health, Rockville Pike, Bethesda, MD 20892, USA
    J Bioenerg Biomembr 40:163-70. 2008
    ..Overall, we demonstrate that VDAC gating is not just an observation made under artificial conditions of channel reconstitution but is a major mechanism of MOM permeability control...
  56. ncbi Palladacycles catalyse the oxidation of critical thiols of the mitochondrial membrane proteins and lead to mitochondrial permeabilization and cytochrome c release associated with apoptosis
    Debora P Santana
    Centro Interdisciplinar de Investigação Bioquímica CIIB, Universidade de Mogi das Cruzes UMC, Av Dr Cândido Xavier de Almeida e Souza, 200 Mogi das Cruzes, Sao Paulo, Brazil
    Biochem J 417:247-56. 2009
    ..Besides the contribution to clarify the pro-apoptotic mechanism of PdC, this study shows that the catalysis of specific protein thiol cross-linkage is enough to induce mitochondrial permeabilization and cytochrome c release...
  57. pmc Dynamics of mitochondrial structure during apoptosis and the enigma of Opa1
    Ryuji Yamaguchi
    Burnham Institute for Medical Science, 10901 N Torrey Pines Rd, La Jolla, CA 92037, USA
    Biochim Biophys Acta 1787:963-72. 2009
    ..We review the recent literature pertaining to the coordinated release of cytochrome c during cell death...
  58. 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
    ..Transient dissipation of Deltapsi(m) 6 h after infection is essential for the induction of macrophage necrosis by Mtb, a mechanism that allows further dissemination of the pathogen and development of the disease...
  59. pmc Protective effect of geranylgeranylacetone via enhancement of HSPB8 induction in desmin-related cardiomyopathy
    Atsushi Sanbe
    Department of Pharmacology, National Research Institute for Child Health and Development, Tokyo, Japan
    PLoS ONE 4:e5351. 2009
    ..While we have shown that small HSPs can directly interrupt amyloid oligomer formation, the in vivo protective effects of the small HSPs on the development of DRM is still uncertain...
  60. ncbi Complexity and diversity in c-type cytochrome biogenesis systems
    J W A Allen
    Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK
    Biochem Soc Trans 33:145-6. 2005
    ..Here we discuss emerging evidence for at least one additional system, for unanticipated diversity in the location of the systems and for the co-existence of multiple systems in some cells...
  61. pmc Cytochrome c biogenesis: the Ccm system
    Carsten Sanders
    Kutztown University, Department of Biology, Kutztown, PA 19530, USA
    Trends Microbiol 18:266-74. 2010
    ....
  62. pmc Apaf-1 and caspase-9 accelerate apoptosis, but do not determine whether factor-deprived or drug-treated cells die
    Paul G Ekert
    The Walter and Eliza Hall Institute for Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia
    J Cell Biol 165:835-42. 2004
    ..Unlike expression of Bcl-2, loss of Apaf-1, caspase-2, or caspase-9 would therefore be unlikely to enhance the survival of cancer cells...
  63. ncbi Gossypol induces Bax/Bak-independent activation of apoptosis and cytochrome c release via a conformational change in Bcl-2
    Xiaobo Lei
    The Laboratory of Apoptosis and Cancer Biology, Institute of Zoology, Chinese Academy of Sciences, Bei Si Huan Xi Road 25, Haidian District, Beijing 100080, PR China
    FASEB J 20:2147-9. 2006
    ..We conclude that gossypol converts the antiapoptotic molecule Bcl-2 into a proapoptotic molecule that can mediate the release of cyto c and induce apoptosis...
  64. ncbi Apoptosis and human diseases: mitochondrion damage and lethal role of released cytochrome C as proapoptotic protein
    P Caroppi
    Dipartimento di Medicina Sperimentale e Scienze Biochimiche, Universita di Roma Tor Vergata, Via Montpellier 1, 00133 Roma, Italy
    Curr Med Chem 16:4058-65. 2009
    ..This review provides an overview of the key role played by mitochondria and cytochrome c in the activation of the apoptotic process...
  65. pmc High glucose disrupts mitochondrial morphology in retinal endothelial cells: implications for diabetic retinopathy
    Kyle Trudeau
    Department of Medicine, Boston University School of Medicine, 650 Albany Street, Boston 02118, USA
    Am J Pathol 177:447-55. 2010
    ....
  66. pmc The role of oxidized cytochrome c in regulating mitochondrial reactive oxygen species production and its perturbation in ischaemia
    Philippe Pasdois
    School of Biochemistry and The Bristol Heart Institute, University of Bristol, Bristol BS8 1TD, UK
    Biochem J 436:493-505. 2011
    ..We further suggest that in hypoxia, production of H₂O₂ to activate signalling pathways may be also mediated by decreased oxidized cytochrome c and less superoxide scavenging...
  67. ncbi Bak activation for apoptosis involves oligomerization of dimers via their alpha6 helices
    Grant Dewson
    The Walter and Eliza Hall Institute of Medical Research, Melbourne, Parkville Victoria, Australia
    Mol Cell 36:696-703. 2009
    ..We conclude that alpha6:alpha6 interaction occurs during Bak oligomerization and proapoptotic function, but we find no evidence that zinc binding to that interface regulates apoptosis...
  68. ncbi Inhibiting Drp1-mediated mitochondrial fission selectively prevents the release of cytochrome c during apoptosis
    J Estaquier
    Unité de Physiopathologie des Infections Lentivirales, Institut Pasteur, 28 rue du Dr Roux, 75724 Paris Cedex 15, France
    Cell Death Differ 14:1086-94. 2007
    ..Finally, we observed that downregulation of Drp1 delays but does not inhibit apoptosis, suggesting that mitochondrial fragmentation is not a prerequisite for apoptosis...
  69. pmc Loss of caspase-2-dependent apoptosis induces autophagy after mitochondrial oxidative stress in primary cultures of young adult cortical neurons
    Meenakshi Tiwari
    Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, Texas 78229, USA
    J Biol Chem 286:8493-506. 2011
    ..In summary, the present study identifies a novel function of caspase-2 in mitochondrial oxidative stress-induced apoptosis in neurons cultured from young adult mice...
  70. ncbi Role of mitochondria in tamoxifen-induced rapid death of MCF-7 breast cancer cells
    A Kallio
    Department of Anatomy and Medicity Research Laboratory, Institute of Biomedicine, University of Turku, Tykistokatu 6A, 20520 Turku, Finland
    Apoptosis 10:1395-410. 2005
    ..These mechanisms may contribute to the ability of Tam therapy to induce death of breast cancer cells...
  71. ncbi Skeletal muscle and heart LKB1 deficiency causes decreased voluntary running and reduced muscle mitochondrial marker enzyme expression in mice
    D M Thomson
    Dept of Physiology and Developmental Biology, Brigham Young Univ, Provo, UT 84602, USA
    Am J Physiol Endocrinol Metab 292:E196-202. 2007
    ..Capacity for voluntary running is compromised with muscle and heart LKB1 deficiency...
  72. ncbi Mcl-1 interacts with truncated Bid and inhibits its induction of cytochrome c release and its role in receptor-mediated apoptosis
    John G Clohessy
    Molecular Haematology and Cancer Biology Unit, Institute of Child Health and Great Ormond Street Hospital for Children, University College London, 30 Guilford Street, London WC1N 1EH, United Kingdom
    J Biol Chem 281:5750-9. 2006
    ..Therefore, our study demonstrates a novel regulation of tBid by Mcl-1 through protein-protein interaction in apoptotic signaling from death receptors to mitochondria...
  73. pmc Essential requirement of cytochrome c release for caspase activation by procaspase-activating compound defined by cellular models
    M Seervi
    Integrated Cancer Research Program, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, India
    Cell Death Dis 2:e207. 2011
    ..This study for the first time defines precise criteria for the validation of direct caspase-activating compounds using specialized cellular models that is expected to accelerate the discovery of potential direct caspase activators...
  74. ncbi Involvement of Bcl-2 family, cytochrome c and caspase 3 in induction of apoptosis by beauvericin in human non-small cell lung cancer cells
    Hen I Lin
    School of Medicine, Fu Jen Catholic University, 510, Chung Cheng Road, Hsin Chuang, Taipei Hsien 242, Taiwan
    Cancer Lett 230:248-59. 2005
    ....
  75. pmc The ConSurf-DB: pre-calculated evolutionary conservation profiles of protein structures
    Ofir Goldenberg
    Department of Biochemistry, George S Wise Faculty of Life Sciences, Tel Aviv University, Israel
    Nucleic Acids Res 37:D323-7. 2009
    ..The repository is updated with the latest PDB entries on a monthly basis and will be rebuilt annually. ConSurf-DB is available online at http://consurfdb.tau.ac.il/..
  76. pmc The mitochondrial protein Bak is pivotal for gliotoxin-induced apoptosis and a critical host factor of Aspergillus fumigatus virulence in mice
    Julian Pardo
    Metschnikoff Laboratory, Max Planck Institut fur Immunbiologie, D 79108 Freiburg, Germany
    J Cell Biol 174:509-19. 2006
    ..The elucidation of the molecular basis opens new strategies for the development of therapeutic regimens to combat A. fumigatus and related fungal infections...
  77. ncbi Mitochondria-dependent pathway is involved in heat-induced male germ cell death: lessons from mutant mice
    Yanira Vera
    Division of Endocrinology, Department of Medicine, Harbor UCLA Medical Center and Research and Education Institute, Torrance, California 90509, USA
    Biol Reprod 70:1534-40. 2004
    ..Similar events were also noted in both gld and lprcg mice. Taken together, these results indicate that the mitochondria-dependent pathway is the key apoptotic pathway for heat-induced male germ cell death in mice...
  78. ncbi The role of the mitochondrial permeability transition in cell death
    Jeffrey S Armstrong
    Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 8 Medical Drive, Singapore 117597, Singapore
    Mitochondrion 6:225-34. 2006
    ..However, data also suggest that signaling crosstalk between the MPT and Bcl-2 family proteins occurs indicating an important role for the MPT in apoptosis...
  79. ncbi Gliotoxin-mediated apoptosis of activated human hepatic stellate cells
    Young Oh Kweon
    Division of Digestive Diseases and Nutrition, Department of Medicine, CB 7038, Glaxo Research Bldg Rm 156, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
    J Hepatol 39:38-46. 2003
    ..Gliotoxin induces apoptosis of activated human and rat HSCs by an unknown mechanism...
  80. ncbi Mitochondrial fragmentation in apoptosis
    Damien Arnoult
    Unité de Physiopathologie des Infections Lentivirales, Institut Pasteur, 28 rue du Dr Roux, 75724 Paris, Cedex 15, France
    Trends Cell Biol 17:6-12. 2007
    ..Here, I discuss the apparently conflicting data and conclude that mitochondrial fragmentation is probably not a prerequisite for MOMP and cytochrome c release...
  81. ncbi Inhibition of autophagy by 3-MA potentiates cisplatin-induced apoptosis in esophageal squamous cell carcinoma cells
    Donglei Liu
    Department of Thoracic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, 430022 Wuhan, Hubei Province, People s Republic of China
    Med Oncol 28:105-11. 2011
    ..Autophagy might play a role as a self-protective mechanism in DDP-treated esophageal cancer cells, and its inhibition could be a novel strategy for the adjuvant chemotherapy of esophageal cancer...
  82. ncbi Structure of complex III with bound cytochrome c in reduced state and definition of a minimal core interface for electron transfer
    Sozanne R N Solmaz
    Department of Molecular Membrane Biology, Max Planck Institute of Biophysics, 60438 Frankfurt am Main, Germany
    J Biol Chem 283:17542-9. 2008
    ..Four core interactions encircle the heme cofactors surrounded by variable interactions. The core interface may be a feature to gain specificity for formation of the reactive complex...
  83. ncbi Sanguinarine-dependent induction of apoptosis in primary effusion lymphoma cells
    Azhar R Hussain
    Human Cancer Genomic Research, King Fahad National Center for Children s Cancer and Research, Biological and Medical Research, Riyadh 11211, Saudi Arabia
    Cancer Res 67:3888-97. 2007
    ....
  84. pmc HSP72 protects cells from ER stress-induced apoptosis via enhancement of IRE1alpha-XBP1 signaling through a physical interaction
    Sanjeev Gupta
    Apoptosis Research Centre, School of Natural Sciences, NUI Galway, Galway, Ireland
    PLoS Biol 8:e1000410. 2010
    ..Our data show that binding of Hsp72 to IRE1alpha enhances IRE1alpha/XBP1 signaling at the ER and inhibits ER stress-induced apoptosis. These results provide a physical connection between cytosolic chaperones and the ER stress response...
  85. ncbi Inhibition of autophagy by 3-MA enhances the effect of 5-FU-induced apoptosis in colon cancer cells
    Jie Li
    Department of General Surgical Science Surgery I, Graduate School of Medicine, Gunma University, Maebashi, Gunma 371 8511, Japan
    Ann Surg Oncol 16:761-71. 2009
    ..However, 5-FU resistance in the course of treatment has become more common. Therefore, new therapeutic strategies and/or new adjuvant drugs still need to be explored...
  86. pmc Mcl-1 determines the Bax dependency of Nbk/Bik-induced apoptosis
    Bernhard Gillissen
    Department of Hematology, Oncology, and Tumor Immunology, University Medical Center Charite, 13125 Berlin, Germany
    J Cell Biol 179:701-15. 2007
    ..The finding that different BH3-only proteins rely specifically on Bax, Bak, or both has important implications for the design of anticancer drugs targeting Bcl-2...
  87. ncbi Nonpeptidic small-molecule inhibitor of Bcl-2 and Bcl-XL, (-)-Gossypol, enhances biological effect of genistein against BxPC-3 human pancreatic cancer cell line
    Ramzi M Mohammad
    Division of Hematology and Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA
    Pancreas 31:317-24. 2005
    ..Gossypol, a natural polyphenolic compound isolated from cottonseeds, is a dual and potent small-molecule inhibitor of Bcl-2 and Bcl-XL proteins, with a Ki value in the 300-600 nM range for both proteins...
  88. pmc GM1-ganglioside accumulation at the mitochondria-associated ER membranes links ER stress to Ca(2+)-dependent mitochondrial apoptosis
    Renata Sano
    Department of Genetics and Tumor Cell Biology, St Jude Children s Research Hospital, Memphis, TN 38105, USA
    Mol Cell 36:500-11. 2009
    ....
  89. pmc Glucose metabolism determines resistance of cancer cells to bioenergetic crisis after cytochrome-c release
    Heinrich J Huber
    Systems Biology Group, Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, Dublin, Ireland
    Mol Syst Biol 7:470. 2011
    ..Our results provide a quantitative and mechanistic explanation for the protective role of enhanced glucose utilisation for cancer cells to avert the otherwise lethal bioenergetic crisis associated with apoptosis initiation...
  90. ncbi Identification of deficient mitochondrial signaling in apoptosis resistant leukemia cells by flow cytometric analysis of intracellular cytochrome c, caspase-3 and apoptosis
    K Stahnke
    University Children s Hospital, Ulm Germany
    Apoptosis 9:457-65. 2004
    ..Flow cytometric analysis of mitochondrial apoptosis signaling may provide a useful tool for the prediction of drug resistance and treatment failure in primary leukemia...
  91. ncbi Role of HPV E6 proteins in preventing UVB-induced release of pro-apoptotic factors from the mitochondria
    Sabrina Leverrier
    CR UK, Skin Tumour Laboratory, Centre for Cutaneous Research, London, UK
    Apoptosis 12:549-60. 2007
    ..Our results indicate that the E6 activity towards Bak is a key factor that promotes survival of HPV-infected cells that facilitates tumor development...
  92. pmc PUMA is critical for neonatal cardiomyocyte apoptosis induced by endoplasmic reticulum stress
    Philip Nickson
    Boston Biomedical Research Institute, 64 Grove Street, Watertown, MA 02472, USA
    Cardiovasc Res 73:48-56. 2007
    ..Since ischemia/reperfusion is also associated with endoplasmic reticulum (ER) stress, in the present study we investigated whether Puma contributes to the ER stress-dependent component of cardiomyocyte apoptosis...
  93. ncbi Mitochondrial fission factor Drp1 is essential for embryonic development and synapse formation in mice
    Naotada Ishihara
    Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Tokyo 113 8519, Japan
    Nat Cell Biol 11:958-66. 2009
    ....
  94. pmc Brucella melitensis triggers time-dependent modulation of apoptosis and down-regulation of mitochondrion-associated gene expression in mouse macrophages
    Yongqun He
    Unit for Laboratory Animal Medicine, University of Michigan Medical School, 018 Animal Research Facility, 1150 W Medical Center Drive, Ann Arbor, MI 48109, USA
    Infect Immun 74:5035-46. 2006
    ..melitensis 16M appears to inhibit apoptosis of macrophages by blocking release of cytochrome c and production of reactive oxygen species in the mitochondria, thus preventing activation of caspase cascades...
  95. ncbi Matrine upregulates the cell cycle protein E2F-1 and triggers apoptosis via the mitochondrial pathway in K562 cells
    Hua Jiang
    Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China
    Eur J Pharmacol 559:98-108. 2007
    ..These results demonstrate that matrine triggers apoptosis of K562 cells primarily through the mitochondrial pathway and that matrine is a potential anti-tumor drug...
  96. ncbi Activated macrophages utilize glycolytic ATP to maintain mitochondrial membrane potential and prevent apoptotic cell death
    A Garedew
    Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6BT, UK
    Cell Death Differ 17:1540-50. 2010
    ..Our results indicate that during inflammatory activation 'glycolytically competent cells' such as MΦ use significant amounts of the glycolytically generated ATP to maintain ΔΨ(m) and thereby prevent apoptosis...
  97. ncbi Ornithine decarboxylase prevents methotrexate-induced apoptosis by reducing intracellular reactive oxygen species production
    C C Huang
    Tzu Hui Institute of Technology, Pingtung, Taiwan, ROC
    Apoptosis 10:895-907. 2005
    ..The results demonstrate that MTX-induced apoptosis is ROS-dependent and occurs along a mitochondria-mediated pathway. Overexpressed ODC cells are resistant to MTX-induced apoptosis by reducing intracellular ROS production...
  98. ncbi Upstream control of apoptosis by caspase-2 in serum-deprived primary neurons
    D Chauvier
    Theraptosis Research Laboratory, Theraptosis S A, Pasteur Biotop, Institut Pasteur, 25 28 Rue du Docteur Roux, 75015 Paris, France
    Apoptosis 10:1243-59. 2005
    ..Hence, caspase-2 is an early checkpoint for apoptosis initiation in primary neurons subjected to serum deprivation...
  99. ncbi The reaction of neuroglobin with potential redox protein partners cytochrome b5 and cytochrome c
    Angela Fago
    Department of Biological Sciences, C F Møllers Alle 1131, Aarhus University, DK 8000 Aarhus C, Denmark
    FEBS Lett 580:4884-8. 2006
    ..Based on this data we propose that ferrous neuroglobin may well play a role in preventing apoptosis...
  100. ncbi Dietary iron deficiency induces ventricular dilation, mitochondrial ultrastructural aberrations and cytochrome c release: involvement of nitric oxide synthase and protein tyrosine nitration
    Feng Dong
    Division of Pharmaceutical Sciences and Graduate Neuroscience Program, Center for Cardiovascular Research and Alternative Medicine, University of Wyoming, Laramie, WY 82071, USA
    Clin Sci (Lond) 109:277-86. 2005
    ....
  101. ncbi An increase in intracellular Ca2+ is required for the activation of mitochondrial calpain to release AIF during cell death
    E Norberg
    Institute of Environmental Medicine, Division of Toxicology, Karolinska Institutet, Stockholm, Sweden
    Cell Death Differ 15:1857-64. 2008
    ..Inhibition of calpain, or chelation of Ca(2+), but not the suppression of caspase activity, prevented processing and release of AIF. Combined, these results provide novel insights into the mechanism of AIF release during cell death...

Research Grants71

  1. Roles of Nitric Oxide and Superoxide in Cystitis
    ANTHONY JOHN KANAI; Fiscal Year: 2013
    ..Hypothesis: FA-NO2 are radioprotective by desensitizing TRPA1 and TRPV1 channels and BDNF-AB and NGF-AB are therapeutic by inhibiting nerve growth and sensitization in bladder and spinal cord. ..
  2. THE ROLE OF ACETYLATION IN MITOCHONDRIAL FUNCTION
    Gary Cecchini; Fiscal Year: 2013
    ..Using the SIRT3 KO mouse model, it will be determined if the properties of cardiac tissue such as pre- and post-conditioning are altered by acetylation/deacetylation of proteins. ..
  3. Functional Genomics of the Mitochondrial Proteome
    Dennis R Winge; Fiscal Year: 2011
    ..The function of up to 30% of the mitochondrial proteome is unknown. This proposal will elucidate the function of these un-annotated mitochondrial proteins, providing new insights into the role of mitochondria in human disease. ..
  4. Protein Nitration in the Placenta
    Leslie Myatt; Fiscal Year: 2012
    ....
  5. Therapeutic Effect of a Novel Antioxidant on Degenerative Eye Disorders
    Nuran Ercal; Fiscal Year: 2012
    ..NACA eye drops would represent an alternative to costly cataract surgery, reduce health care costs related to age-related eye diseases and greatly improve the quality of life of people affected by these diseases. ..
  6. Role of Mitochondria in the Regulation of Iron metabolism by Alcohol
    DUYGU DEE DEE HARRISON-FINDIK; Fiscal Year: 2012
    ..The knowledge obtained from these studies, characterizing the pivotal role of mitochondria, will enable us to determine the mechanisms of liver injury caused by iron and alcohol in patients with ALD. ..
  7. Genetic Studies of Optic Atrophy
    Taosheng Huang; Fiscal Year: 2012
    ..This study will allow us to understand how mutations of OPA1 cause optic atrophy and explore its novel function in lifespan and provide us a potential opportunity to develop treatments for the disease. ..
  8. Protection of Brain Injury from Cyanide Poisoning by Carnosic Acid
    Stuart A Lipton; Fiscal Year: 2013
    ..To investigate neuroprotective effects of CA in an in vitro model of cyanide poisoning. Specific Aim 2. To examine neuroprotective effects of CA in an in vivo mouse model mimicking the effects of cyanide ingestion. ..
  9. Extracellular ubiquitin: role in myocyte apoptosis and myocardial remodeling
    Krishna Singh; Fiscal Year: 2010
    ....
  10. Prevention of Retinal Degeneration by Crystallins in Experimental Uveitis
    Narsing A Rao; Fiscal Year: 2011
    ..PUBLIC HEALTH RELEVANCE AlphaA crystallin is a unique protein present in the eye and other tissues. Lack of this protein can cause blindness, and supplement of this protein can prevent several blinding diseases. ..
  11. Nanoelectrode arrays for study of the molecular mechanisms, triggers, and inhibit
    Peter J Burke; Fiscal Year: 2012
    ..A high throughput technology to monitor P in mitochondria will allow further studies of these issues in cancer biology. ..
  12. Visualization of ototoxic mitochondrial dysfunction in mammalian hair cells
    Shelley A Batts; Fiscal Year: 2012
    ..Thus, this work could fundamentally affect the way that hearing research is conducted by allowing longitudinal investigations into the intact mammalian cochlea for the first time. ..
  13. TNF-alpha Signaling in Silica-Induced Lung Fibrosis
    Luis A Ortiz; Fiscal Year: 2012
    ..34 and 2.4 years for survival and graft rejection respectively). Consequently, these data indicate that silicosis still is a serious and frequently lethal lung disease for which no successful treatment is available. ..
  14. Mitochondrial function and antifungal photodynamic therapy
    Constantine G Haidaris; Fiscal Year: 2011
    ..abstract_text> ..
  15. Mitochondrial Protection Within Chronically Ischemic Myocardium
    Edward O McFalls; Fiscal Year: 2010
    ..Using this model, we propose that a class of drugs used in diabetic patients that has been associated with heart failure exacerbations, alters the mitochondrial energy production in a similar way. ..
  16. Research Center for Pharmacology &Drug Toxicology
    L Jackson Roberts; Fiscal Year: 2013
    ....
  17. Role of Mitochondria Targeted CYP2E1 and HO-1 in Alcohol Mediated Tissue Injury
    Narayan G Avadhani; Fiscal Year: 2012
    ..The proposed research project is based on the hypothesis that mitochondrially targeted CYP2E1 and HO-1 contribute to ROS production, oxidative stress and mitochondrial dysfunction as important factors leading to tissue injury. ..
  18. Targeting ATAP-mediated Apoptosis in Treatment of Prostate Cancer
    Zelin Sheng; Fiscal Year: 2013
    ....
  19. Alcoholic Liver Dysfunction Potentiation by Hyperlipidemia and Cigarette Smoke
    SHANNON MARIE BAILEY; Fiscal Year: 2013
    ....
  20. Role of The Jak-Stat Pathway in Ischemic Preconditioning
    Yu Ting Xuan; Fiscal Year: 2010
    ..This proposal will provide important new insights into the signaling and molecular mechanisms whereby the late phase of ischemic PC reprograms the heart in the intact animal. ..
  21. Investigation of underlying mechanisms of sex differences in cerebral ischemia
    Chad S Siegel; Fiscal Year: 2010
    ..The overall goal of this proposal is to investigate mechanisms underlying sex differences in ischemic cell death. ..
  22. Chemoprevention of Pancreatic Cancer by Capsaicin
    Sanjay K Srivastava; Fiscal Year: 2013
    ..Successful completion of this project will support the development and clinical application of capsaicin for the chemoprevention of pancreatic cancer. ..
  23. Function of mRNA Editing in Trypanosomes
    Stephen L Hajduk; Fiscal Year: 2010
    ..Together these studies will provide the first analysis of the role of RNA editing in protein diversification in trypanosomes and is likely to lead to the discovery of novel mitochondrial proteins. ..
  24. Mechanisms of Cell Death after Photodynamic Therapy
    Anna Liisa Nieminen; Fiscal Year: 2010
    ..The proposed studies will enhance our understanding how to enhance PDT-induced killing of cancer cells and further increase the efficacy of PDT translation to the benefit for cancer patients. ..
  25. PROTEIN KINASE C IN THE LENS
    DOLORES JEAN TAKEMOTO; Fiscal Year: 2010
    ..Activation of these enzymes, using targeted drugs, could prevent or delay ocular damage during oxidative insult or ischemia. ..
  26. Obesity related pancreatic fat worsens local injury via unsaturated fatty acids
    VIJAY PREM SINGH; Fiscal Year: 2013
    ..These studies could open a new therapeutic frontier for this devastating disease by targeting specific lipases(s) and by stratifying patients according to risk of severe AP based on findings of IPF on imaging studies. ..
  27. The in vivo role of the mitochondrial p53 cell death program
    UTE MARTHA MOLL; Fiscal Year: 2013
    ..This is the thrust of this proposal. Furthermore, this proposal aims at gaining more mechanistic insight into how p53 works at the mitochondria to permeabilize these organelles. ..
  28. Role of a pro-apoptotic Bcl-2 protein in the survival and death of leukemia cells
    Ameeta Kelekar; Fiscal Year: 2013
    ....
  29. Molecular Pathogenesis of Coenzyme Q10 Deficiency
    Michio Hirano; Fiscal Year: 2012
    ..Aim 4: In collaboration with Professor Pl[unreadable]cido Navas, University of Sevilla, Spain, we will characterize CoQ10 biosynthetic genes and mutations in yeast. ..
  30. The Hig1 protein family and the cytochrome c oxidase complex
    Rosemary A Stuart; Fiscal Year: 2012
    ....
  31. Modulation of Mitochondrial Function by Pro-Oxidants
    LUKE IGNATIUS SZWEDA; Fiscal Year: 2010
    ..Our studies seek to define age-related factors that enhance the severity of heart disease in an effort to design strategies to improve the outcome. ..
  32. Structure and function analysis of C1/C1q and MBL using a novel peptide inhibitor
    NEEL KUMAR KRISHNA; Fiscal Year: 2012
    ....
  33. Kinase/Phosphatase-mediated Mitochondrial Restructuring in Neuroprotection
    Stefan Strack; Fiscal Year: 2012
    ....
  34. HPV, Tumor Metabolism and Radiosensitivity in Head and Neck Cancer
    Hyeong Reh Choi Kim; Fiscal Year: 2013
    ..Completion of this exploratory R21 application will help us understand molecular basis for HPV-associated radiosensitivity and provide important information for further patient stratification and the design of biomarker-driven therapy. ..
  35. Regulation of mitochondrial oxidative stress by Bcl-2 family proteins
    DANIEL LINSEMAN; Fiscal Year: 2011
    ..PHS 398/2590 (Rev. 09/04, Reissued 4/2006) Page Continuation Format Page ..
  36. Diabetes Erectile dysfunction and apoptosis of cavernous tissues
    Rajvir Dahiya; Fiscal Year: 2010
    ..Accomplishment of these experiments will provide novel molecular mechanisms of erectile dysfunction and can help guide us towards the development of new therapies for the treatment of erectile dysfunction. ..
  37. Antioxidants and Antiinflammatory in Colorectal Cancer
    Ah Ng Tony Kong; Fiscal Year: 2012
    ..This is an R01 competing application to study the mechanism of dietary phytochemicals isothiocyanates (sulforaphane and PEITC) and phenolic compounds (curcumin and DBM) alone or in combination against colorectal cancer. ..
  38. Oxidative Lipidomics in Pediatric Traumatic Brain Injury
    Hulya Bayir; Fiscal Year: 2012
    ..We will test novel compounds in experiments to prevent oxidative stress and neuronal death after TBI. The ability to selectively modulate this pathway could lead to targeted therapies for TBI and ultimately improve outcome for children. ..
  39. Molecular Probes of the Mechanisms of Cytocrhome P450
    JOHN TAYLOR GROVES; Fiscal Year: 2013
    ..abstract_text> ..
  40. Alkylammonium Formate Mobile Phase Modifiers for Protein Liquid Chromatography
    NEIL DANIELSON; Fiscal Year: 2009
    ..This will benefit the pharmaceutical industry and biotech companies as well as academic or government research programs with an interest in proteins and enzymes as drugs or reagents to facilitate medical research. ..
  41. Molecular mechanisms of chemoresistance in breast cancer
    Manabu Kurokawa; Fiscal Year: 2013
    ..Moreover, this work will provide me with the means to establish myself as an independent investigator. ..
  42. In vivo mechanisms of methamphetamine-induced neuronal necrosis
    Denson G Fujikawa; Fiscal Year: 2013
    ..Our finding that METH-induced subclinical RESDs in mice are associated with widespread neuronal damage could have important translational applicability. ..
  43. Mitochondrial Proteins in Parkinson's Disease
    J Timothy Greenamyre; Fiscal Year: 2013
    ....
  44. Kinase/Phosphatase-mediated Mitochondrial Restructuring in Neuroprotection
    Stefan Strack; Fiscal Year: 2013
    ..The proposed studies will increase our mechanistic understanding of mitochondrial fragmentation and its regulation by reversible phosphorylation in neurons, which may lead to better therapies for neurodegeneration in stroke and disease. ..
  45. Copper Uptake from Plasma Ceruloplasmin
    Maria C Linder; Fiscal Year: 2012
    ....
  46. Pharmacogenomics of Human P450 Oxidoreductase
    Walter L Miller; Fiscal Year: 2012
    ..This project explores a third possibility, a gene called POR, that is needed for the activity of drug-metabolizing enzymes. ..
  47. Impact of Exercise on Sarcopenia
    Judd M Aiken; Fiscal Year: 2013
    ..An important outcome of these studies is to determine if endurance training, a commonly employed intervention of sarcopenia, can be beneficial to muscle health in old mammals. 1 ..
  48. ROLE OF OXIDIZED CARDIOLIPIN TRANSLOCATION IN OXIDATIVE STRESS-INDUCED APOPTOSIS
    Albert W Girotti; Fiscal Year: 2010
    ..The research is also biomedically significant, considering the numerous pathological conditions associated with oxidative stress, many of which, including several cardiovascular disorders, are characterized by apoptogenic tissue damage. ..
  49. Proteinuria causes progressive kidney disease by impairing autophagy
    Andrea Havasi; Fiscal Year: 2013
    ..I believe that this NIH mentored award will promote my scientific maturity and allow me to transition to a level that will make me competitive for independent research support. ..
  50. Cellular Functions of Parkin
    Jian Feng; Fiscal Year: 2013
    ..Our studies will also provide novel targets for the development of more effective therapies for Parkinson's disease. ..
  51. c-Src/EGF Receptors Interactions and Therapeutic Resistance in Breast Cancer
    Sarah J Parsons; Fiscal Year: 2010
    ..Our studies aim to achieve a better understanding of which cancers demonstrate pY845-dependent resistance to therapy, so that we can target this pathway for intervention. ..
  52. Spectroscopic Studies of Active Sites in Copper Proteins
    Edward I Solomon; Fiscal Year: 2011
    ..abstract_text> ..
  53. NEUROCHEMICAL PHARMACOLOGY OF PHENCYCLIDINE
    Kenneth Johnson; Fiscal Year: 2009
    ..The potential role of CREB dephosphorylation as a result of over activation of NMDA receptors will also be assessed in the neurotoxicity of PCP treatment. ..
  54. TARGETS OF AMINO ACID RESTRICTION IN PROSTATE CANCER
    Gary G Meadows; Fiscal Year: 2009
    ..This research could serve as the basis for future development of more specific antimetastatic, anti-invasive, apoptosis-based therapies for human prostate cancer. ..
  55. Mitochondrial Fission in Huntington's Disease
    ELLA R BOSSY-WETZEL; Fiscal Year: 2013
    ....
  56. NEUROTROPHIC FACTOR MODULATION OF CORNEAL ENDOTHELIUM
    Shay Whey Koh; Fiscal Year: 2009
    ..abstract_text> ..
  57. Mapping Lipid Oxidation in Traumatic Brain Injury by Mass Spectrometric Imaging
    Valerian E Kagan; Fiscal Year: 2013
    ..Overall, IMS technology and the underlying contribution of dyshomeostasis of mitochondrial CL and extramitochondrial PS are likely to be important for TBI studies and have implications for other CNS disorders. ..
  58. Mechanisms of Hypothermic Protection from Ischemia/Reperfusion Cardiac Injury
    Kimm J Hamann; Fiscal Year: 2010
    ....
  59. Targeting Hexokinase II in Chemotherapy
    John G Pastorino; Fiscal Year: 2012
    ....
  60. ENERGY TRANSDUCTION IN CYTOCHROME OXIDASE
    SHELAGH M FERGUSON-MILLER; Fiscal Year: 2013
    ....
  61. Oxidative Stress and Vascular HO in Diabetes
    Nader G Abraham; Fiscal Year: 2010
    ..It will allow for the first time, an in-depth analysis of the function of HO-1 in vascular protection and for the development of innovative gene-targeting therapies for the treatment of type I diabetes. ..
  62. Cell Death/Survival After Global Cerebral Ischemia
    Pak H Chan; Fiscal Year: 2013
    ..abstract_text> ..
  63. REACTION MECHANISM OF MYOCARDIAC UBIQUINONE-PROTEINS
    Chang An Yu; Fiscal Year: 2009
    ..site pocket, the proton transfer path, structure water, hydrogen bonding, and the interaction domain between cytochromes c\ and c...
  64. Cardiolipin Function in Mitochondrial Electron-Transfer Complexes
    Neal C Robinson; Fiscal Year: 2011
    ..Successful completion of this project will determine the absolute requirement for cardiolipin and help us understand its pathophysiological importance. ..
  65. ELECTRON-TRANSFER PROTEINS
    FRANCIS S contact MILLETT; Fiscal Year: 2010
    ..In the proposed studies, new ruthenium photoexcitation methods will be developed to study electron transfer reactions important to human health. ..
  66. Role of Subunit III in Cytochrome Oxidase Function
    Jonathan Hosler; Fiscal Year: 2007
    ..unreadable] [unreadable]..
  67. FREE RADICALS, PROTEIN AGGREGATES & PARKINSON'S DISEASE
    GARY PIELAK; Fiscal Year: 2001
    ..Site-specific variants of both proteins will used to locate the radicals in the primary structure. Mass spectrometry and amino acid analysis will be used to demonstrate crosslinking, and SDS PAGE will be used to assess aggregation. ..
  68. Elucidating the Biosynthesis and Transport of Heme A
    ERIC HEGG; Fiscal Year: 2006
    ..abstract_text> ..
  69. ELECTRON TRANSFER IN DYNAMIC PROTEIN COMPLEXES
    JAMES ERMAN; Fiscal Year: 2009
    ....
  70. HTS for Cytochrome C Synthesis Pathways
    Robert G Kranz; Fiscal Year: 2011
    ..Thus, the HTS will also discover new inhibitors of heme biosynthesis, and the PIs group has developed the tools to quickly determine which enzyme (of nine) is inhibited in heme synthesis. ..
  71. DETERMINANTS OF FUNCTIONAL DIVERSITY IN HEME ENZYMES
    DAVID GOODIN; Fiscal Year: 1993
    ..5. The gene for horseradish peroxidase C will be synthesized and expressed in E. coli to allow comparative mutagenesis studies now in progress with cytochrome c peroxidase...