Valerian Kagan

Summary

Affiliation: University of Pittsburgh
Country: USA

Publications

  1. ncbi Interplay between bax, reactive oxygen species production, and cardiolipin oxidation during apoptosis
    Jianfei Jiang
    Center for Free Radical and Antioxidant Health, Department of Environmental and Occupational Health, University of Pittsburgh, Bridgeside Point, 100 Technology Drive, Suite 350, Pittsburgh, PA 15219, USA
    Biochem Biophys Res Commun 368:145-50. 2008
  2. ncbi Carbon nanotubes degraded by neutrophil myeloperoxidase induce less pulmonary inflammation
    Valerian E Kagan
    Department of Environmental and Occupational Health, Center for Free Radical and Antioxidant Health, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
    Nat Nanotechnol 5:354-9. 2010
  3. ncbi Factoring-in agglomeration of carbon nanotubes and nanofibers for better prediction of their toxicity versus asbestos
    Ashley R Murray
    Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV, USA
    Part Fibre Toxicol 9:10. 2012
  4. ncbi Oxidative signaling pathway for externalization of plasma membrane phosphatidylserine during apoptosis
    V E Kagan
    Department of Environmental and Occupational Health, University of Pittsburgh, 260 Kappa Drive, Pittsburgh, PA 15238, USA
    FEBS Lett 477:1-7. 2000
  5. ncbi 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
  6. ncbi Endogenously generated hydrogen peroxide is required for execution of melphalan-induced apoptosis as well as oxidation and externalization of phosphatidylserine
    Tatsuya Matsura
    Division of Medical Biochemistry, Department of Pathophysiological and Therapeutic Science, Faculty of Medicine, Tottori University, 86 NIshi cho, Yonago 683 8503, Japan
    Chem Res Toxicol 17:685-96. 2004
  7. ncbi Mitochondrial targeting of electron scavenging antioxidants: Regulation of selective oxidation vs random chain reactions
    Valerian E Kagan
    Center for Free Radical and Antioxidant Health, University of Pittsburgh, PA 15219, USA
    Adv Drug Deliv Rev 61:1375-85. 2009
  8. ncbi Appetizing rancidity of apoptotic cells for macrophages: oxidation, externalization, and recognition of phosphatidylserine
    V E Kagan
    Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA 15260, USA
    Am J Physiol Lung Cell Mol Physiol 285:L1-17. 2003
  9. ncbi Toward oxidative lipidomics of cell signaling
    Valerian E Kagan
    Department of Environmental and Occupational Health University of Pittsburgh, Pittsburgh, PA 15260, USA
    Antioxid Redox Signal 6:199-202. 2004
  10. ncbi Oxidative lipidomics of apoptosis: redox catalytic interactions of cytochrome c with cardiolipin and phosphatidylserine
    Valerian E Kagan
    Center for Free Radical and Antioxidant Health, Department of Environmental and Occupational Health, Pittsburgh, PA 15260, USA
    Free Radic Biol Med 37:1963-85. 2004

Research Grants

  1. Carbon Nanotube Biodegradation by Neutrophil Myeloperoxidase
    Valerian E Kagan; Fiscal Year: 2010
  2. Oxidative lipidomics of pulmonary endothelial apoptosis in hyperoxia
    Valerian E Kagan; Fiscal Year: 2010
  3. Irradiation Damage and Protection of Pulmonary Endothelium Oxidative Lipidomics
    Valerian Kagan; Fiscal Year: 2009
  4. Oxidative lipidomics of pulmonary endothelial apoptosis in hyperoxia
    Valerian Kagan; Fiscal Year: 2009
  5. Lung Oxidative Stress/Inflammation By Carbon Nanotubes
    Valerian Kagan; Fiscal Year: 2007
  6. Lung Oxidative Stress/Inflammation By Carbon Nanotubes
    Valerian Kagan; Fiscal Year: 2005
  7. Pulmonary Phosphatidylserine Oxidation in Apoptosis
    Valerian Kagan; Fiscal Year: 2005
  8. COPPER/ALBUMIN REDOX-CYCLING IN PREECLAMPSIA
    Valerian Kagan; Fiscal Year: 2003
  9. Irradiation Damage and Protection of Pulmonary Endothelium Oxidative Lipidomics
    Valerian E Kagan; Fiscal Year: 2010

Detail Information

Publications82

  1. ncbi Interplay between bax, reactive oxygen species production, and cardiolipin oxidation during apoptosis
    Jianfei Jiang
    Center for Free Radical and Antioxidant Health, Department of Environmental and Occupational Health, University of Pittsburgh, Bridgeside Point, 100 Technology Drive, Suite 350, Pittsburgh, PA 15219, USA
    Biochem Biophys Res Commun 368:145-50. 2008
    ..Thus, cardiolipin peroxidation may be causatively and time-dependently related to Bax/Bak effects on ROS generation and peroxidase activation of cytochrome c...
  2. ncbi Carbon nanotubes degraded by neutrophil myeloperoxidase induce less pulmonary inflammation
    Valerian E Kagan
    Department of Environmental and Occupational Health, Center for Free Radical and Antioxidant Health, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
    Nat Nanotechnol 5:354-9. 2010
    ..Our findings suggest that the extent to which carbon nanotubes are biodegraded may be a major determinant of the scale and severity of the associated inflammatory responses in exposed individuals...
  3. ncbi Factoring-in agglomeration of carbon nanotubes and nanofibers for better prediction of their toxicity versus asbestos
    Ashley R Murray
    Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV, USA
    Part Fibre Toxicol 9:10. 2012
    ..While the toxicity and hazardous outcomes elicited by airborne exposure to single-walled CNT or asbestos have been widely reported, very limited data are currently available describing adverse effects of respirable CNF...
  4. ncbi Oxidative signaling pathway for externalization of plasma membrane phosphatidylserine during apoptosis
    V E Kagan
    Department of Environmental and Occupational Health, University of Pittsburgh, 260 Kappa Drive, Pittsburgh, PA 15238, USA
    FEBS Lett 477:1-7. 2000
    ..Thus, cytochrome c-mediated phosphatidylserine oxidation may represent an important component of the apoptotic pathway...
  5. ncbi 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...
  6. ncbi Endogenously generated hydrogen peroxide is required for execution of melphalan-induced apoptosis as well as oxidation and externalization of phosphatidylserine
    Tatsuya Matsura
    Division of Medical Biochemistry, Department of Pathophysiological and Therapeutic Science, Faculty of Medicine, Tottori University, 86 NIshi cho, Yonago 683 8503, Japan
    Chem Res Toxicol 17:685-96. 2004
    ....
  7. ncbi Mitochondrial targeting of electron scavenging antioxidants: Regulation of selective oxidation vs random chain reactions
    Valerian E Kagan
    Center for Free Radical and Antioxidant Health, University of Pittsburgh, PA 15219, USA
    Adv Drug Deliv Rev 61:1375-85. 2009
    ..Particular emphasis is placed on the employment of triphenylphosphonium- and hemi-gramicidin S-moieties as two effective vehicles for mitochondrial delivery of antioxidants...
  8. ncbi Appetizing rancidity of apoptotic cells for macrophages: oxidation, externalization, and recognition of phosphatidylserine
    V E Kagan
    Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA 15260, USA
    Am J Physiol Lung Cell Mol Physiol 285:L1-17. 2003
    ..The putative importance of this oxidative phosphatidylserine signaling in lung physiology and disease are also discussed...
  9. ncbi Toward oxidative lipidomics of cell signaling
    Valerian E Kagan
    Department of Environmental and Occupational Health University of Pittsburgh, Pittsburgh, PA 15260, USA
    Antioxid Redox Signal 6:199-202. 2004
    ....
  10. ncbi Oxidative lipidomics of apoptosis: redox catalytic interactions of cytochrome c with cardiolipin and phosphatidylserine
    Valerian E Kagan
    Center for Free Radical and Antioxidant Health, Department of Environmental and Occupational Health, Pittsburgh, PA 15260, USA
    Free Radic Biol Med 37:1963-85. 2004
    ..We also show that this new concept is compatible with a leading role for reactive oxygen species in the execution of the apoptotic program, with cyt c as the main executioner...
  11. ncbi Targeting nitroxides to mitochondria: location, location, location, and ...concentration: highlight commentary on "Mitochondria superoxide dismutase mimetic inhibits peroxide-induced oxidative damage and apoptosis: role of mitochondrial superoxide&qu
    Valerian E Kagan
    Center for Free Radical and Antioxidant Health, Department of Environmental and Occupational Health, University of Pittsburgh, Bridgeside Point, 100 Technology Drive, Suite 333, Pittsburgh, PA 15219, USA
    Free Radic Biol Med 43:348-50. 2007
  12. ncbi A role for oxidative stress in apoptosis: oxidation and externalization of phosphatidylserine is required for macrophage clearance of cells undergoing Fas-mediated apoptosis
    Valerian E Kagan
    Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA 15260, USA
    J Immunol 169:487-99. 2002
    ..Taken together, our data suggest that the presence of PS-OX in conjunction with nonoxidized PS on the cell surface is an important signal for macrophage clearance of apoptotic cells...
  13. ncbi Mishandling of copper by albumin: role in redox-cycling and oxidative stress in preeclampsia plasma
    V E Kagan
    Department of Environmental and Occupational Health, and Magee Womens Research Institute, University of Pittsburgh, Pittsburgh, Pennsylvania 15238, USA
    Hypertens Pregnancy 20:221-41. 2001
    ....
  14. ncbi Nanomedicine and nanotoxicology: two sides of the same coin
    Valerian E Kagan
    Center for Free Radical and Antioxidant Health, Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA
    Nanomedicine 1:313-6. 2005
    ....
  15. ncbi Toward mechanism-based antioxidant interventions: lessons from natural antioxidants
    Valerian E Kagan
    Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA
    Ann N Y Acad Sci 959:188-98. 2002
    ..Experiments are now underway to determine whether inhibition of PS oxidation by antioxidants may interfere with important signaling functions of oxidative stress in eliminating apoptotic cells...
  16. ncbi Pro-oxidant and antioxidant mechanisms of etoposide in HL-60 cells: role of myeloperoxidase
    V E Kagan
    Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15238, USA
    Cancer Res 61:7777-84. 2001
    ....
  17. ncbi Antioxidant mechanisms of nitric oxide against iron-catalyzed oxidative stress in cells
    V E Kagan
    Department of Environmental and Occupational Health, University of Pittsburgh, PA 15238, USA
    Antioxid Redox Signal 3:189-202. 2001
    ..In the latter pathway, NO down-regulates expression of iron-containing proteins to prevent their catalytic prooxidant reactions...
  18. ncbi Mitochondria-targeted disruptors and inhibitors of cytochrome c/cardiolipin peroxidase complexes: a new strategy in anti-apoptotic drug discovery
    Valerian E Kagan
    Center for Free Radical and Antioxidant Health, University of Pittsburgh, Pittsburgh, PA 15219 3130, USA
    Mol Nutr Food Res 53:104-14. 2009
    ..Therefore, mitochondria-targeted disruptors and inhibitors of cyt c/CL peroxidase complexes and suppression of CL peroxidation represent new strategies in anti-apoptotic drug discovery...
  19. ncbi NADPH oxidase-dependent oxidation and externalization of phosphatidylserine during apoptosis in Me2SO-differentiated HL-60 cells. Role in phagocytic clearance
    Antonio Arroyo
    Department of Environmental and Occupational Health, Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA 15260, USA
    J Biol Chem 277:49965-75. 2002
    ....
  20. ncbi Anti-/pro-oxidant effects of phenolic compounds in cells: are colchicine metabolites chain-breaking antioxidants?
    Martin Modriansky
    Department of Environmental and Occupational Health, University of Pittsburgh, FORBL Room 234, 3343 Forbes Avenue, Pittsburgh, PA 15260, USA
    Toxicology 177:105-17. 2002
    ..However, the latter retain high reactivity towards critical biomolecules in cells such as lipids, thiols, ascorbate, thereby, rendering colchicine metabolites effective radical scavengers but not effective chain-breaking antioxidants...
  21. ncbi Peroxidation and externalization of phosphatidylserine associated with release of cytochrome c from mitochondria
    Jianfei Jiang
    Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA 15260, USA
    Free Radic Biol Med 35:814-25. 2003
    ....
  22. ncbi Effects of MnSOD-plasmid liposome gene therapy on antioxidant levels in irradiated murine oral cavity orthotopic tumors
    Michael W Epperly
    Department of Radiation Oncology, University of Pittsburgh Cancer Institute and School of Public Health, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213, USA
    Radiat Res 167:289-97. 2007
    ..Thus normal tissue radioprotective MnSOD-PL gene therapy radiosensitizes tumor cell lines in vitro and has a therapeutic effect on orthotopic tumors in part through its effects on tumor antioxidants...
  23. ncbi Vitamin E inhibits anti-Fas-induced phosphatidylserine oxidation but does not affect its externalization during apoptosis in Jurkat T cells and their phagocytosis by J774A.1 macrophages
    Behice F Serinkan
    Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA 15260, U.S.A
    Antioxid Redox Signal 6:227-36. 2004
    ..1 macrophages. We conclude that vitamin E does not significantly interfere with extrinsic (death receptor-triggered) pathways of apoptosis and does not affect phagocytosis of anti-Fas-triggered apoptotic cells...
  24. ncbi Lipid antioxidant, etoposide, inhibits phosphatidylserine externalization and macrophage clearance of apoptotic cells by preventing phosphatidylserine oxidation
    Yulia Y Tyurina
    Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA
    J Biol Chem 279:6056-64. 2004
    ....
  25. ncbi Cardiolipin-specific peroxidase reactions of cytochrome C in mitochondria during irradiation-induced apoptosis
    Natalia A Belikova
    Center for Free Radical and Antioxidant Health, University of Pittsburgh, Pittsburgh, PA, USA
    Int J Radiat Oncol Biol Phys 69:176-86. 2007
    ..To determine whether cytochrome c (cyt c) content and associated cardiolipin oxidation can be determinants of cell sensitivity to irradiation-induced apoptosis...
  26. ncbi Arachidonic acid-induced carbon-centered radicals and phospholipid peroxidation in cyclo-oxygenase-2-transfected PC12 cells
    Jianfei Jiang
    Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA
    J Neurochem 90:1036-49. 2004
    ..Thus, COX-2 generated carbon-centered radicals but not oxygen radicals or thiyl radicals are responsible for oxidative stress in AA-challenged PC12 cells overexpressing COX-2...
  27. ncbi Nitroxides scavenge myeloperoxidase-catalyzed thiyl radicals in model systems and in cells
    Grigory G Borisenko
    Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA
    J Am Chem Soc 126:9221-32. 2004
    ..Furthermore, Ac-Tempo preserved intracellular GSH and protected cells from phenol/GS(*) toxicity, suggesting a new mechanism for the free-radical scavenging activity of nitroxides in live cells...
  28. ncbi Quantification of selective phosphatidylserine oxidation during apoptosis
    James P Fabisiak
    Department of Environmental and Occupational Health, University of Pittsburgh, PA, USA
    Methods Mol Biol 291:449-56. 2005
    ..These experimental approaches can provide insight into the roles and mechanisms of PS oxidation in the identification and clearance of apoptotic cells...
  29. ncbi Assessment of antioxidant reserves and oxidative stress in cerebrospinal fluid after severe traumatic brain injury in infants and children
    Hulya Bayir
    Department of Anesthesiology and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
    Pediatr Res 51:571-8. 2002
    ..Progressive compromise of antioxidant defenses and evidence of free radical-mediated lipid peroxidation are noted. These markers could be used to monitor antioxidant strategies in clinical trials...
  30. ncbi Glutathione propagates oxidative stress triggered by myeloperoxidase in HL-60 cells. Evidence for glutathionyl radical-induced peroxidation of phospholipids and cytotoxicity
    Grigory G Borisenko
    Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA
    J Biol Chem 279:23453-62. 2004
    ..Thus, GSH, commonly viewed as a universal free radical scavenger and major intracellular antioxidant, acts as a pro-oxidant during myeloperoxidase-catalyzed metabolism of phenol in HL-60 cells...
  31. ncbi A mitochondria-targeted nitroxide/hemigramicidin S conjugate protects mouse embryonic cells against gamma irradiation
    Jianfei Jiang
    Center for Medical Countermeasures Against Radiation, University of Pittsburgh, Pittsburgh, PA 15219, USA
    Int J Radiat Oncol Biol Phys 70:816-25. 2008
    ....
  32. ncbi The plasma membrane is the site of selective phosphatidylserine oxidation during apoptosis: role of cytochrome C
    Yulia Y Tyurina
    Department of Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
    Antioxid Redox Signal 6:209-25. 2004
    ..Selective plasma membrane-based PS oxidation and subsequent externalization during oxidant-induced apoptosis may be mediated through the redox activity of cytochrome c...
  33. ncbi Hemigramicidin-TEMPO conjugates: novel mitochondria-targeted antioxidants
    Mitchell P Fink
    Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA
    Crit Care Med 35:S461-7. 2007
    ..Compounds like XJB-5-131 warrant further evaluation for the treatment of hemorrhagic shock as well as other acute conditions associated with increased mitochondrial production of ROS...
  34. ncbi 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
    ....
  35. ncbi Redox sensor function of metallothioneins
    James P Fabisiak
    Department of Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA
    Methods Enzymol 353:268-81. 2002
    ....
  36. ncbi Peroxidation of phosphatidylserine in mechanisms of apoptotic signaling
    Yulia Y Tyurina
    Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA
    Methods Enzymol 352:159-74. 2002
  37. ncbi Selective early cardiolipin peroxidation after traumatic brain injury: an oxidative lipidomics analysis
    Hulya Bayir
    Center for Free Radical and Antioxidant Health, University of Pittsburgh, Pittsburgh, PA, USA
    Ann Neurol 62:154-69. 2007
    ..Enhanced lipid peroxidation is well established in traumatic brain injury. However, its molecular targets, identity of peroxidized phospholipid species, and their signaling role have not been deciphered...
  38. ncbi The hierarchy of structural transitions induced in cytochrome c by anionic phospholipids determines its peroxidase activation and selective peroxidation during apoptosis in cells
    Alexander A Kapralov
    Center for Free Radical and Antioxidant Health, Department of Environmental and Occupational Health, University of Pittsburgh, PA 15260, USA
    Biochemistry 46:14232-44. 2007
    ....
  39. ncbi Oxidation of phosphatidylserine: a mechanism for plasma membrane phospholipid scrambling during apoptosis?
    Yulia Y Tyurina
    Center for Free Radical and Antioxidant Health, Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA 15260, USA
    Biochem Biophys Res Commun 324:1059-64. 2004
    ..PSox did not inhibit APT. Rate of transmembrane PS diffusion was fourfold higher in cells with integrated PSox than with PS. Thus, PSox acts as a "non-enzymatic scramblase" likely contributing to PS externalization...
  40. ncbi Depletion of Bcl-2 by an antisense oligonucleotide induces apoptosis accompanied by oxidation and externalization of phosphatidylserine in NCI-H226 lung carcinoma cells
    Patrick P Koty
    Department of Environmental and Occupational Health, University of Pittsburgh Graduate School of Public Health, PA, USA
    Mol Cell Biochem 234:125-33. 2002
    ..This observed externalization of PS may facilitate the 'labeling' of apoptotic cells for recognition by macrophage scavenger receptors and subsequent phagocytic clearance...
  41. ncbi Hemigramicidin-TEMPO conjugates: novel mitochondria-targeted anti-oxidants
    Mitchell P Fink
    Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, United States
    Biochem Pharmacol 74:801-9. 2007
    ..quot; One of these hemigramicidin-TEMPO conjugates, XJB-5-131, has been shown to ameliorate intestinal mucosal injury and prolong survival in rats subjected to lethal hemorrhage...
  42. ncbi Heterolytic reduction of fatty acid hydroperoxides by cytochrome c/cardiolipin complexes: antioxidant function in mitochondria
    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
    J Am Chem Soc 131:11288-9. 2009
    ..Regulation of FFA-OOH metabolism may be an important function of cyt c that is associated with elimination of toxic FFA-OOH and synthesis of physiologically active hydroxy-fatty acids in mitochondria...
  43. ncbi Nitrosative stress inhibits the aminophospholipid translocase resulting in phosphatidylserine externalization and macrophage engulfment: implications for the resolution of inflammation
    Yulia Y Tyurina
    Center for Free Radical and Antioxidant Health, Department of Environmental and Occupational Health, and Cancer Institute, University of Pittsburgh, Pittsburgh, Pennsylvania 15219, USA
    J Biol Chem 282:8498-509. 2007
    ..scavenger, DAF-2. Thus, macrophage-induced nitrosylation/oxidation plays an important role in cell clearance, and hence in the resolution of inflammation...
  44. ncbi Mechanisms of cardiolipin oxidation by cytochrome c: relevance to pro- and antiapoptotic functions of etoposide
    Yulia Y Tyurina
    Center for Free Radical and Antioxidant Health, Department of EOH, Bridgeside Point, 100 Technology Drive, Suite 350, Pittsburgh, PA 15219, USA
    Mol Pharmacol 70:706-17. 2006
    ..Thus, oxidation of cardiolipin by the cytochrome c/cardiolipin peroxidase complex, which is essential for apoptosis, is not inhibited by proapoptotic concentrations of the drug...
  45. ncbi Activation of NO donors in mitochondria: peroxidase metabolism of (2-hydroxyamino-vinyl)-triphenyl-phosphonium by cytochrome c releases NO and protects cells against apoptosis
    Detcho A Stoyanovsky
    Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USA
    FEBS Lett 582:725-8. 2008
    ....
  46. ncbi Nitric oxide inhibits peroxidase activity of cytochrome c.cardiolipin complex and blocks cardiolipin oxidation
    Irina I Vlasova
    Center for Free Radical and Antioxidant Health, Department of Environmental and Occupational Health, University of Pittsburgh, 100 Technology Drive, Pittsburgh, PA 15260, USA
    J Biol Chem 281:14554-62. 2006
    ..NO effectively inhibited 1,1'2,2'-tertalinoleoyl cardiolipin oxidation catalyzed by the peroxidase activity of cyt c. Thus, NO can act as a regulator of peroxidase activity of cyt c.CL complexes...
  47. ncbi Macrophage recognition of externalized phosphatidylserine and phagocytosis of apoptotic Jurkat cells--existence of a threshold
    Grigory G Borisenko
    Department of Environmental and Occupational Health, University of Pittsburgh, 3343 Forbes Avenue, PA 15260, USA
    Arch Biochem Biophys 413:41-52. 2003
    ....
  48. ncbi Quantitative method of measuring phosphatidylserine externalization during apoptosis using electron paramagnetic resonance spectroscopy and annexin-conjugated iron
    James P Fabisiak
    Department of Environmental and Occupational Health, University of Pittsburgh, PA, USA
    Methods Mol Biol 291:457-64. 2005
    ....
  49. ncbi Structural requirements for optimized delivery, inhibition of oxidative stress, and antiapoptotic activity of targeted nitroxides
    Jianfei Jiang
    Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA 15219, USA
    J Pharmacol Exp Ther 320:1050-60. 2007
    ..These new insights into the structure-activity relationships of nitroxide-peptide and -peptide isostere conjugates are instrumental for development of new mechanism-based therapeutically effective agents...
  50. ncbi Cytochrome c release is required for phosphatidylserine peroxidation during Fas-triggered apoptosis in lung epithelial A549 cells
    Jianfei Jiang
    Department of Environmental and Occupational Health, Center for Free Radical and Antioxidant Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA
    Lipids 39:1133-42. 2004
    ..Overall, we concluded that cyt c acts as a catalyst of PtdSer oxidation during Fas-triggered A549 cell apoptosis...
  51. ncbi MnSOD-plasmid liposome gene therapy decreases ionizing irradiation-induced lipid peroxidation of the esophagus
    Michael W Epperly
    Department of Radiation Oncology, University of Pittsburgh Cancer Institute and School of Environmental Health, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA
    In Vivo 19:997-1004. 2005
    ..The biochemical combination of superoxide and nitric oxide radicals forms peroxynitrite, a potent oxidant known to induce lipid peroxidation...
  52. ncbi Bench-to-bedside review: Mitochondrial injury, oxidative stress and apoptosis--there is nothing more practical than a good theory
    Hulya Bayir
    Safar Center for Resuscitation Research, Department of Critical Care Medicine, School of Medicine, University of Pittsburgh, PA, USA
    Crit Care 12:206. 2008
    ....
  53. ncbi Cardiolipin deficiency leads to decreased cardiolipin peroxidation and increased resistance of cells to apoptosis
    Zhentai Huang
    Center for Free Radical and Antioxidant Health, Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA 15219, USA
    Free Radic Biol Med 44:1935-44. 2008
    ....
  54. ncbi Quantification of oxidative/nitrosative modification of CYS(34) in human serum albumin using a fluorescence-based SDS-PAGE assay
    James P Fabisiak
    Department of Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh, 3343 Forbes Avenue, Pittsburgh, PA 15238, USA
    Antioxid Redox Signal 4:855-65. 2002
    ....
  55. ncbi Derivatization of F2-isoprostanes with 1-pyrenyldiazomethane and their subsequent determination by fluorescence high-performance liquid chromatography
    Vladimir B Ritov
    Department of Medicine, School of Medicine, Division of Endocrinology and Metabolism, University of Pittsburgh, 3459 Fifth Avenue, MUH N809, Pittsburgh, PA 15213 3236, USA
    Anal Biochem 311:10-8. 2002
    ..The purified 1-pyrenylmethyl esters of PGF(2alpha) were quantitatively analyzed by reverse-phase HPLC with fluorescent detection, with a detection limit of 5-10 pg...
  56. ncbi Peroxidase mechanism of lipid-dependent cross-linking of synuclein with cytochrome C: protection against apoptosis versus delayed oxidative stress in Parkinson disease
    Hulya Bayir
    Center for Free Radical and Antioxidant Health, Pittsburgh Institute for Neurodegenerative Diseases, University of Pittsburgh, Pittsburgh, Pennsylvania 15219 3130, USA
    J Biol Chem 284:15951-69. 2009
    ..This immediate protective function of Syn is associated with the formation of the peroxidase complex representing a source of oxidative stress and postponed damage...
  57. ncbi Contribution of glutathione and metallothioneins to protection against copper toxicity and redox cycling: quantitative analysis using MT+/+ and MT-/- mouse lung fibroblast cells
    Jianfei Jiang
    Department of Environmental and Occupational Health, University of Pittsburgh, 3343 Forbes Avenue, Pittsburgh, PA 15260, USA
    Chem Res Toxicol 15:1080-7. 2002
    ..Cu-induced toxicity was remarkably higher in BSO/Zn-pretreated MT-/- cells than in naive or Zn-pretreated cells, although slightly lower than in the MT-/- cells pretreated with BSO alone...
  58. ncbi Phosphatidylserine peroxidation/externalization during staurosporine-induced apoptosis in HL-60 cells
    Tatsuya Matsura
    Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA 15260, USA
    FEBS Lett 524:25-30. 2002
    ..These findings are compatible with our proposed roles for oxidative PS-dependent signaling during apoptosis and phagocytosis...
  59. ncbi Peroxidase activity of hemoglobin-haptoglobin complexes: covalent aggregation and oxidative stress in plasma and macrophages
    Alexandr Kapralov
    Center for Free Radical and Antioxidant Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15219, USA
    J Biol Chem 284:30395-407. 2009
    ....
  60. ncbi The mitochondria-targeted nitroxide JP4-039 augments potentially lethal irradiation damage repair
    Malolan S Rajagopalan
    Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA
    In Vivo 23:717-26. 2009
    ..These results establish a potential role of mitochondria-targeted nitroxide drugs as mitigators of radiation damage to quiescent cells including stem cells...
  61. ncbi Mass-spectrometric characterization of phospholipids and their hydroperoxide derivatives in vivo: effects of total body irradiation
    Yulia Y Tyurina
    Center for Free Radical and Antioxidant Health and Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA, USA
    Methods Mol Biol 580:153-83. 2009
    ..The protocols described may be utilized in studies of signaling functions of oxidized phospholipids in cell physiology and pathology...
  62. ncbi Oxidative lipidomics of apoptosis: quantitative assessment of phospholipid hydroperoxides in cells and tissues
    Vladimir A Tyurin
    Center for Free Radical and Antioxidant Health, Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA, USA
    Methods Mol Biol 610:353-74. 2010
    ..This has important implications for evaluation of apoptosis in vivo. The anionic phospholipids, cardiolipin (CL) and phosphatidylserine (PS), are the preferred peroxidation substrates...
  63. ncbi Oxidative lipidomics of hyperoxic acute lung injury: mass spectrometric characterization of cardiolipin and phosphatidylserine peroxidation
    Yulia Y Tyurina
    Center for Free Radical and Antioxidant Health, Dept of Environmental and Occupational Health, Univ of Pittsburgh, Bridgeside Point, 100 Technology Drive, Suite 350, Pittsburgh, PA 15219, USA
    Am J Physiol Lung Cell Mol Physiol 299:L73-85. 2010
    ....
  64. ncbi Ascorbate as a "redox sensor" and protector against irradiation-induced oxidative stress in 32D CL 3 hematopoietic cells and subclones overexpressing human manganese superoxide dismutase
    Michael W Epperly
    Department of Radiation Oncology, University of Pittsburgh, Pittsburgh, PA, USA
    Int J Radiat Oncol Biol Phys 58:851-61. 2004
    ....
  65. ncbi Mass-spectrometric analysis of hydroperoxy- and hydroxy-derivatives of cardiolipin and phosphatidylserine in cells and tissues induced by pro-apoptotic and pro-inflammatory stimuli
    Vladimir A Tyurin
    Center for Free Radical and Antioxidant Health, University of Pittsburgh, Pittsburgh, PA 15219 9361, USA
    J Chromatogr B Analyt Technol Biomed Life Sci 877:2863-72. 2009
    ....
  66. 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...
  67. ncbi Nitric oxide and zinc homeostasis in acute lung injury
    Claudette M St Croix
    Department of Environmental and Occupational Health, University of Pittsburgh Graduate School Public Health, Pittsburgh, PA 15260, USA
    Proc Am Thorac Soc 2:236-42. 2005
    ....
  68. ncbi Mitochondrial targeting of selective electron scavengers: synthesis and biological analysis of hemigramicidin-TEMPO conjugates
    Peter Wipf
    Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA
    J Am Chem Soc 127:12460-1. 2005
    ..Our delivery approach is based on the use of specific structural signaling features recognizable by cells as mitochondria targeting sequences and offers considerable therapeutic anti-apoptotic potential...
  69. ncbi Treatment with a novel hemigramicidin-TEMPO conjugate prolongs survival in a rat model of lethal hemorrhagic shock
    Carlos A Macias
    Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA
    Ann Surg 245:305-14. 2007
    ..We sought to develop a therapeutic agent that would permit prolongation of survival in rats subjected to lethal hemorrhagic shock (HS), even in the absence of resuscitation with asanguinous fluids or blood...
  70. ncbi Cardiolipin switch in mitochondria: shutting off the reduction of cytochrome c and turning on the peroxidase activity
    Liana V Basova
    Center for Free Radical and Antioxidant Health, Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA
    Biochemistry 46:3423-34. 2007
    ..Thus, both redox properties and functions of cyt c change upon interaction with CL in the mitochondrial membrane, diminishing cyt c's electron donor/acceptor role and stimulating its peroxidase activity...
  71. ncbi Vitamin E deficiency enhances pulmonary inflammatory response and oxidative stress induced by single-walled carbon nanotubes in C57BL/6 mice
    Anna A Shvedova
    Pathology Physiology Research Branch, HELD, NIOSH, Morgantown, WV, USA
    Toxicol Appl Pharmacol 221:339-48. 2007
    ..Given that pulmonary levels of vitamin E can be manipulated through diet, its effects on SWCNT-induced inflammation may be of practical importance in optimizing protective strategies...
  72. ncbi Thioredoxin and lipoic acid catalyze the denitrosation of low molecular weight and protein S-nitrosothiols
    Detcho A Stoyanovsky
    Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA
    J Am Chem Soc 127:15815-23. 2005
    ..We conclude that both thioredoxin and dihydrolipoic acid may be involved in the regulation of cellular S-nitrosothiols...
  73. ncbi Selective peroxidation and externalization of phosphatidylserine in normal human epidermal keratinocytes during oxidative stress induced by cumene hydroperoxide
    Anna A Shvedova
    Health Effects Laboratory Division, Pathology and Physiology Research Branch, NIOSH, Morgantown, West Virginia 26505, USA
    J Invest Dermatol 118:1008-18. 2002
    ..This would make them targets for macrophage recognition and phagocytosis, and thus limit their potential to invoke inflammation or give rise to neoplastic transformations...
  74. ncbi Apoptosis and macrophage clearance of neutrophils: regulation by reactive oxygen species
    Bengt Fadeel
    Division of Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
    Redox Rep 8:143-50. 2003
    ..This review aims to address the latter topic, as well as to summarize current knowledge on the molecular mechanisms of neutrophil apoptosis and macrophage clearance of these cells at the site of inflammation...
  75. ncbi Prevention of catecholaminergic oxidative toxicity by 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl and its recycling complex with polynitroxylated albumin, TEMPOL/PNA
    Ariella Weinberg
    Pediatric Center for Neuroscience, Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, PA 15213, USA
    Brain Res 1012:13-21. 2004
    ..PNA enhances the therapeutic index of TEMPOL, and the recycling antioxidant that results from their adjunctive administration may prove useful in disorders involving oxidative stress...
  76. ncbi S-nitrosoalbumin-mediated relaxation is enhanced by ascorbate and copper: effects in pregnancy and preeclampsia plasma
    Robin E Gandley
    Magee Womens Research Institute and Department of Environmental and Occupational Health, University of Pittsburgh, 204 Craft Ave, Pittsburgh, PA 15213, USA
    Hypertension 45:21-7. 2005
    ..We suggest that the higher circulating levels of SNO-Alb, in women with preeclampsia, reflect a deficiency in Asc/Cu-mediated release of NO from SNO-Alb...
  77. ncbi The intracellular domain of p75NTR as a determinant of cellular reducing potential and response to oxidant stress
    Yulia Y Tyurina
    Pediatric Center for Neuroscience, Children's Hospital of Pittsburgh, Pittsburgh, PA 15213, USA
    Aging Cell 4:187-96. 2005
    ....
  78. ncbi Bcl-2-mediated potentiation of neocarzinostatin-induced apoptosis: requirement for caspase-3, sulfhydryl groups, and cleavable Bcl-2
    Zhiping Mi
    Division of Child Neurology, Pediatric Center for Neuroscience, Children's Hospital of Pittsburgh of UPMC, PA 15213, USA
    Cancer Chemother Pharmacol 57:357-67. 2006
    ..These results definitively demonstrate the requirement for caspase-3, cleavable Bcl-2, and available sulfhydryl groups (separate from those required for NCS activation) in potentiation of NCS-induced apoptosis by Bcl-2...
  79. ncbi An epigrammatic (abridged) recounting of the myriad tales of astonishing deeds and dire consequences pertaining to nitric oxide and reactive oxygen species in mitochondria with an ancillary missive concerning the origins of apoptosis
    Diane E Heck
    Departments of Pharmacology and Toxicology, Rutgers University, Piscataway, NJ 08854, USA
    Toxicology 208:259-71. 2005
    ....
  80. ncbi Unusual inflammatory and fibrogenic pulmonary responses to single-walled carbon nanotubes in mice
    Anna A Shvedova
    Health Effects Laboratory Div, NIOSH, Morgantown, WV, USA
    Am J Physiol Lung Cell Mol Physiol 289:L698-708. 2005
    ..Equal doses of ultrafine carbon black particles or fine crystalline silica (SiO2) did not induce granulomas or alveolar wall thickening and caused a significantly weaker pulmonary inflammation and damage...
  81. ncbi Quantitation of S-nitrosothiols in cells and biological fluids
    Vladimir A Tyurin
    Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA
    Methods Enzymol 352:347-60. 2002
  82. ncbi Thiol oxidation enforces phosphatidylserine externalization in apoptosis-sensitive and -resistant cells through a deltapsim/cytochrome C release-dependent mechanism
    A Johanna Forsberg
    Department of Cancer Biology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA
    Antioxid Redox Signal 6:203-8. 2004
    ..These results suggest that although cell death and PS externalization are both cytochrome c-dependent, they are distinct and separable processes...

Research Grants18

  1. Carbon Nanotube Biodegradation by Neutrophil Myeloperoxidase
    Valerian E Kagan; Fiscal Year: 2010
    ....
  2. Oxidative lipidomics of pulmonary endothelial apoptosis in hyperoxia
    Valerian E Kagan; Fiscal Year: 2010
    ....
  3. Irradiation Damage and Protection of Pulmonary Endothelium Oxidative Lipidomics
    Valerian Kagan; Fiscal Year: 2009
    ....
  4. Oxidative lipidomics of pulmonary endothelial apoptosis in hyperoxia
    Valerian Kagan; Fiscal Year: 2009
    ....
  5. Lung Oxidative Stress/Inflammation By Carbon Nanotubes
    Valerian Kagan; Fiscal Year: 2007
    ..abstract_text> ..
  6. Lung Oxidative Stress/Inflammation By Carbon Nanotubes
    Valerian Kagan; Fiscal Year: 2005
    ....
  7. Pulmonary Phosphatidylserine Oxidation in Apoptosis
    Valerian Kagan; Fiscal Year: 2005
    ..This will aid in developing new strategies for directed modulation of inflammation in lung disease. ..
  8. COPPER/ALBUMIN REDOX-CYCLING IN PREECLAMPSIA
    Valerian Kagan; Fiscal Year: 2003
    ....
  9. Irradiation Damage and Protection of Pulmonary Endothelium Oxidative Lipidomics
    Valerian E Kagan; Fiscal Year: 2010
    ....