Calcineurin-mediated BAD dephosphorylation activates the caspase-3 apoptotic cascade in traumatic spinal cord injury

J. E. Springer, R. D. Azbill, S. A. Nottingham, S. E. Kennedy

Research output: Contribution to journalArticlepeer-review

187 Scopus citations

Abstract

We report here that activation of the caspase-3 apoptotic cascade in spinal cord injury is regulated, in par by calcineurin-mediated BAD dephosphorylation. BAD, a proapoptotic member of the bcl-2 gene family, is rapidly dephosphorylated after injury, dissociates from 14-3-3 in the cytosol, and translocates to the mitochondria of neurons where it binds to Bcl-x(L). Pretreatment of animals with FK506, a potent inhibitor of calcineurin activity, or MK801, an NMDA glutamate receptor antagonist, blocked BAD dephosphorylation and abolished activation of the caspase-3 apoptotic cascade. These findings extend previous in vitro observations and are the first to implicate the involvement of glutamate-mediated calcineurin activation and BAD dephosphorylation as upstream, premitochondrial signaling events leading to caspase-3 activation in traumatic spinal cord injury.

Original languageEnglish
Pages (from-to)7246-7251
Number of pages6
JournalJournal of Neuroscience
Volume20
Issue number19
DOIs
StatePublished - Oct 1 2000

Keywords

  • BAD translocation
  • Bcl-xL
  • Calcineurin
  • Caspase-3
  • FK506
  • Glutamate receptors
  • NMDA

ASJC Scopus subject areas

  • General Medicine

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