Identification of Bax-interacting proteins in oligodendrocyte progenitors during glutamate excitotoxicity and perinatal hypoxia-ischemia

Sopio Simonishvili, Mohit Raja Jain, Hong Li, Steven W. Levison, Teresa L. Wood

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


OPC (oligodendrocyte progenitor cell) death contributes significantly to the pathology and functional deficits following hypoxic-ischemic injury in the immature brain and to deficits resulting from demyelinating diseases, trauma and degenerative disorders in the adult CNS. Glutamate toxicity is a major cause of oligodendroglial death in diverse CNS disorders, and previous studies have demonstrated that AMPA/kainate receptors require the pro-apoptotic protein Bax in OPCs undergoing apoptosis. The goal of the present study was to define the pro-apoptotic and anti-apoptotic effectors that regulate Bax in healthy OPCs and after exposure to excess glutamate in vitro and following H-I (hypoxia-ischemia) in the immature rat brain. We show that Bax associates with a truncated form of Bid, a BH3-only domain protein, subsequent to glutamate treatment. Furthermore, glutamate exposure reduces Bax association with the anti-apoptotic Bcl family member, Bcl-xL. Cell fractionation studies demonstrated that both Bax and Bid translocate from the cytoplasm to mitochondria during the early stages of cell death consistent with a role for Bid as an activator, whereas Bcl-xL, which normally complexes with both Bax and Bid, disassociates from these complexes when OPCs are exposed to excess glutamate. Bax remained unactivated in the presence of insulin-like growth factor-1, and the Bcl-xL complexes were protected. Our data similarly demonstrate loss of Bcl-xL-Bax association in white matter following H-I and implicate active Bad in Bax-mediated OPC death. To identify other Bax-binding partners, we used proteomics and identified cofilin as a Bax-associated protein in OPCs. Cofilin and Bax associated in healthy OPCs, whereas the Bax-cofilin association was disrupted during glutamate-induced OPC apoptosis.

Original languageEnglish (US)
Article numbere00131
Pages (from-to)377-390
Number of pages14
JournalASN neuro
Issue number5
StatePublished - 2013

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Clinical Neurology


  • Apoptosis
  • Bcl-xL
  • Bid
  • Cofilin
  • Insulin-like growth factor 1 (IGF-I)
  • Oligodendrocyte

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