RGD Reference Report - Identification of Bax-interacting proteins in oligodendrocyte progenitors during glutamate excitotoxicity and perinatal hypoxia-ischemia. - Rat Genome Database

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

Authors: Simonishvili, S  Jain, MR  Li, H  Levison, SW  Wood, TL 
Citation: Simonishvili S, etal., ASN Neuro. 2013 Dec 23;5(5):e00131. doi: 10.1042/AN20130027.
RGD ID: 10053669
Pubmed: PMID:24195677   (View Abstract at PubMed)
PMCID: PMC3891358   (View Article at PubMed Central)
DOI: DOI:10.1042/AN20130027   (Journal Full-text)

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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
BCL2L1HumanBrain Hypoxia-Ischemia  ISOBcl2l1 (Rattus norvegicus) RGD 
Bcl2l1RatBrain Hypoxia-Ischemia  IDA  RGD 
Bcl2l1MouseBrain Hypoxia-Ischemia  ISOBcl2l1 (Rattus norvegicus) RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Cfl1Ratcellular response to insulin-like growth factor stimulus  IDA  RGD 

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
BaxRatprotein binding  IPICfl1 (Rattus norvegicus) RGD 
Cfl1Ratprotein binding  IPIBax (Rattus norvegicus) RGD 

Objects Annotated

Genes (Rattus norvegicus)
Bax  (BCL2 associated X, apoptosis regulator)
Bcl2l1  (Bcl2-like 1)
Cfl1  (cofilin 1)

Genes (Mus musculus)
Bcl2l1  (BCL2-like 1)

Genes (Homo sapiens)
BCL2L1  (BCL2 like 1)


Additional Information