Oxidative stress induces p53-mediated apoptosis in glia: p53 transcription-independent way to die. (Articolo in rivista)

Type
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  • Oxidative stress induces p53-mediated apoptosis in glia: p53 transcription-independent way to die. (Articolo in rivista) (literal)
Anno
  • 2004-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1002/jnr.10822 (literal)
Alternative label
  • Paolo Bonini1; Simona Cicconi4; Alessio Cardinale2; Cristina Vitale3; Annalucia Serafino4; Mariateresa Ciotti5; Lionel NJL Marlier4 (2004)
    Oxidative stress induces p53-mediated apoptosis in glia: p53 transcription-independent way to die.
    in Journal of neuroscience research
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Paolo Bonini1; Simona Cicconi4; Alessio Cardinale2; Cristina Vitale3; Annalucia Serafino4; Mariateresa Ciotti5; Lionel NJL Marlier4 (literal)
Pagina inizio
  • 83 (literal)
Pagina fine
  • 95 (literal)
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  • Impact Factor 3.727 (literal)
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  • 75 (literal)
Rivista
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  • 1 (literal)
Note
  • ISI Web of Science (WOS) (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • 1 Department of Internal Medicine, University of Rome Tor Vergata, Rome, Italy; 2 Department of Neuroscience, University of Rome Tor Vergata, Rome, Italy; 3 Department of Medical Science, San Raffaele Roma Hospital, Rome, Italy; 4 CNR, INMM, Section of Molecular Medicine, Signal Transduction of Apoptotic Mechanisms Laboratory, Rome, Italy; 5 CNR, INMM, Section of Neuroscience, Rome, Italy (literal)
Titolo
  • Oxidative stress induces p53-mediated apoptosis in glia: p53 transcription-independent way to die. (literal)
Abstract
  • Oxidative stress has been implicated in the pathogenesis of stroke, traumatic brain injuries, and neurodegenerative diseases affecting both neuronal and glial cells in the central nervous system (CNS). The tumor suppressor protein p53 plays a pivotal function in neuronal apoptosis triggered by oxidative stress. We investigated the role of p53 and related molecular mechanisms that support oxidative stress-induced apoptosis in glia. For this purpose, we exposed C6 glioma cells and primary cultures of rat cortical astrocytes to an H(2)O(2)-induced oxidative stress protocol followed by a recovery period. We evaluated the effects of pifithrin-alpha (PF-alpha), which has been reported to protect neurons from ischemic insult by specifically inhibiting p53 DNA-binding activity. Strikingly, PF-alpha was unable to prevent oxidative stress-induced astrocyte apoptosis. We demonstrate that p53 is able to mediate an apoptotic response by direct signaling at mitochondria, despite its transcriptional activity. The z-VAD-fmk-sensitive apoptotic response requires a caspase-dependent MDM-2 degradation, leading to p53 mitochondrial targeting accompanied by cytochrome c release and nucleosomal fragmentation. (literal)
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