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Protein S blocks the extrinsic apoptotic cascade in tissue plasminogen activator/N-methyl D-aspartate-treated neurons via Tyro3-Akt-FKHRL1 signaling pathway

By Huang Guo, Theresa M Barrett, Zhihui Zhong, José A Fernández, John H Griffin, Robert S Freeman and Berislav V Zlokovic
Topics: Research Article
Publisher: BioMed Central
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Provided by: PubMed Central

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  1. (2003). A: Intracellular mechanisms of cyclosporin A-induced tubular cell apoptosis.
  2. (2001). A: The proteolytic activity of tissue-plasminogen activator enhances NMDA receptor-mediated signaling. Nat Med
  3. (2005). Abrams TA: Both protein S and Gas6 stimulate outer segment phagocytosis by cultured rat retinal pigment epithelial cells. Exp Eye Res
  4. (2007). Activation of phosphatidylinositol 3-kinase/protein kinase B pathway by a vanadyl compound mediates its neuroprotective effect in mouse brain ischemia. Neuroscience
  5. (2007). Active FKHRL1 overcomes imatinib resistance in chronic myelogenous leukemia-derived cell lines via the production of tumor necrosis factorrelated apoptosis-inducing ligand. Cancer Sci
  6. (2002). Adjuvant treatment with neuroserpin increases the therapeutic window for tissue-type plasminogen activator administration in a rat model of embolic stroke. Circulation
  7. (2005). Analysis of combined treatment of embolic stroke in rat with r-tPA and a GPIIb/IIIa inhibitor. J Cereb Blood Flow Metab
  8. (2009). Angelillo-Scherrer A: Generation and phenotypic analysis of protein S-deficient mice. Blood
  9. (2004). Arden KC: FoxOs at the crossroads of cellular metabolism, differentiation, and transformation. Cell
  10. (2010). Arora V: Thrombolysis with plasmin: implications for stroke treatment. Stroke
  11. (2010). Barsan WG: Thrombolytic Therapy for Acute Ischemic Stroke beyond Three Hours. J Emerg Med
  12. (1999). Burgering BM: Direct control of the Forkhead transcription factor AFX by protein kinase B. Nature
  13. C: Anti-NR1 N-terminaldomain vaccination unmasks the crucial action of tPA on NMDAreceptor-mediated toxicity and spatial memory. JC e l lS c i2007,
  14. (2010). Chang JY: Chamaecypanone C, a novel skeleton microtubule inhibitor, with anticancer activity by trigger caspase 8-Fas/FasL dependent apoptotic pathway in human cancer cells. Biochem Pharmacol
  15. (2003). Coffer PJ: FOXO transcription factors as regulators of immune homeostasis: molecules to die for?
  16. (1999). Comparative effects of tissue plasminogen activator, streptokinase, and staphylokinase on cerebral ischemic infarction and pulmonary clot lysis in hamster models. Circulation
  17. (2002). Cross-talk between Akt, p53 and Mdm2: possible implications for the regulation of apoptosis. Oncogene
  18. (2009). D: NR2Dcontaining NMDA receptors mediate tissue plasminogen activatorpromoted neuronal excitotoxicity. Cell Death Differ
  19. (2001). DB: A phosphatidylinositol 3-kinase/Akt pathway promotes translocation of Mdm2 from the cytoplasm to the nucleus. Proc Natl Acad Sci USA
  20. (1995). DN: Evidence for a protein S receptor(s) on human vascular smooth muscle cells. Analysis of the binding characteristics and mitogenic properties of protein S on human vascular smooth muscle cells.
  21. (2005). Ethanolwithdrawal seizures are controlled by tissue plasminogen activator via modulation of NR2B-containing NMDA receptors. Proc Natl Acad Sci USA
  22. (2000). Expression of the receptor protein-tyrosine kinases Tyro-3, Axl, and mer in the developing rat central nervous system.
  23. (1997). G: Interleukin-3-induced phosphorylation of BAD through the protein kinase Akt. Science
  24. (2005). GK: Akt contributes to neuroprotection by hypothermia against cerebral ischemia in rats.
  25. (1997). Greenberg ME: Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Cell
  26. (1999). Greenberg ME: Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell
  27. (2004). Intravenous administration of a GPIIb/IIIa receptor antagonist extends the therapeutic window of intra-arterial tenecteplase-tissue plasminogen activator in a rat stroke model. Stroke
  28. (2008). JP: National US estimates of recombinant tissue plasminogen activator use: ICD-9 codes substantially underestimate. Stroke
  29. (2009). Lack of protein S in mice causes embryonic lethal coagulopathy and vascular dysgenesis.
  30. (2001). Lemke G: Homeostatic regulation of the immune system by receptor tyrosine kinases of the Tyro 3 family. Science
  31. (2006). Lemke G: TAM receptor function in the retinal pigment epithelium. Mol Cell Neurosci
  32. (1999). Lemke G: Tyro-3 family receptors are essential regulators of mammalian spermatogenesis.
  33. (2010). Levine SR: Alteplase for ischaemic stroke–much sooner is much better. Lancet
  34. (2003). Lo EH: Lipoprotein receptormediated induction of matrix metalloproteinase by tissue plasminogen activator. Nat Med
  35. (2006). McMasters KM: Adenovirus-mediated gene transfer of FKHRL1 triple mutant efficiently induces apoptosis in melanoma cells. Cancer Biol Ther
  36. (2004). Molecular mechanisms of glutamatedependent neurodegeneration in ischemia and traumatic brain injury. Cell Mol Life Sci
  37. (2001). Moskowitz MA: BID mediates neuronal cell death after oxygen/glucose deprivation and focal cerebral ischemia. Proc Natl Acad Sci USA
  38. (2010). Neurodegeneration and the neurovascular unit. Nat Med
  39. (1998). Phosphatidylinositol 3-kinase and Akt protein kinase are necessary and sufficient for the survival of nerve growth factor-dependent sympathetic neurons.
  40. (2008). Pietrzik CU: The functional role of the second NPXY motif of the LRP1 beta-chain in tissue-type plasminogen activator-mediated activation of N-methyl-D-aspartate receptors.
  41. (1998). SA: Tissue plasminogen activator (tPA) increases neuronal damage after focal cerebral ischemia in wild-type and tPA-deficient mice. Nat Med
  42. (2008). Shacter E: Auto-oxidation and oligomerization of protein S on the apoptotic cell surface is required for Mer tyrosine kinase-mediated phagocytosis of apoptotic cells.
  43. (2009). Speciesspecific anticoagulant and mitogenic activities of murine protein S. Haematologica
  44. (2007). TAM receptors are pleiotropic inhibitors of the innate immune response. Cell
  45. (1997). The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group: Intracerebral hemorrhage after intravenous t-PA therapy for ischemic stroke. Stroke
  46. (1995). The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group: Tissue plasminogen activator for acute ischemic stroke.
  47. (2007). The tale of protein S and C4b-binding protein, a story of affection. Thromb Haemost
  48. (2003). Tissue plasminogen activator and NMDA receptor cleavage. Nat Med
  49. (2009). Tissue-type plasminogen activator in the ischemic brain: more than a thrombolytic. Trends Neurosci
  50. (2003). Tissue-type plasminogen activator induces opening of the blood-brain barrier via the LDL receptor-related protein.
  51. (2007). Tissue-type plasminogen activator-mediated shedding of astrocytic low-density lipoprotein receptor-related protein increases the permeability of the neurovascular unit. Blood
  52. (2008). Toward safer thrombolytic agents in stroke: molecular requirements for NMDA receptor-mediated neurotoxicity. J Cereb Blood Flow Metab
  53. (2010). Tymianski M: Glutamate receptors, neurotoxicity and neurodegeneration. Pflugers Arch
  54. (2010). Wiendl H: Collateral neuronal apoptosis in CNS gray matter during an oligodendrocyte-directed CD8(+) T cell attack. Glia
  55. (2006). Zlokovic BV: Activated protein C inhibits tissue plasminogen activatorinduced brain hemorrhage. Nat Med
  56. (2004). Zlokovic BV: Activated protein C prevents neuronal apoptosis via protease activated receptors 1 and 3. Neuron
  57. (2009). Zlokovic BV: Neuroprotective activities of activated protein C mutant with reduced anticoagulant activity.
  58. (2010). Zlokovic BV: Pericyte-specific expression of PDGF beta receptor in mouse models with normal and deficient PDGF beta receptor signaling. Mol Neurodegener
  59. (2010). Zlokovic BV: Pericytes control key neurovascular functions and neuronal phenotype in the adult brain and during brain aging. Neuron
  60. (2003). Zlokovic BV: Protein S confers neuronal protection during ischemic/hypoxic injury in mice. Circulation
  61. (2010). Zlokovic BV: Protein S protects neurons from excitotoxic injury by activating the TAM receptor Tyro-PI3K-Akt pathway through its SHBG-like region.
  62. (2004). Zlokovic BV: Tissue plasminogen activator neurovascular toxicity is controlled by activated protein C. Nat Med