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Full Length Bid is sufficient to induce apoptosis of cultured rat hippocampal neurons
- Source :
- BMC Cell Biology, Vol 8, Iss 1, p 7 (2007), BMC Cell Biology
- Publication Year :
- 2007
- Publisher :
- Springer Science and Business Media LLC, 2007.
-
Abstract
- BackgroundBcl-2 homology domain (BH) 3-only proteins are pro-apoptotic proteins of the Bcl-2 family that couple stress signals to the mitochondrial cell death pathways. The BH3-only protein Bid can be activated in response to death receptor activation via caspase 8-mediated cleavage into a truncated protein (tBid), which subsequently translocates to mitochondria and induces the release of cytochrome-C. Using a single-cell imaging approach of Bid cleavage and translocation during apoptosis, we have recently demonstrated that, in contrast to death receptor-induced apoptosis, caspase-independent excitotoxic apoptosis involves a translocation of full length Bid (FL-Bid) from the cytosol to mitochondria. We induced a delayed excitotoxic cell death in cultured rat hippocampal neurons by a 5-min exposure to the glutamate receptor agonist N-methyl-D-aspartate (NMDA; 300 μM).ResultsWestern blot experiments confirmed a translocation of FL-Bid to the mitochondria during excitotoxic apoptosis that was associated with the release of cytochrome-C from mitochondria. These results were confirmed by immunofluorescence analysis of Bid translocation during excitotoxic cell death using an antibody raised against the amino acids 1–58 of mouse Bid that is not able to detect tBid. Finally, inducible overexpression of FL-Bid or a Bid mutant that can not be cleaved by caspase-8 was sufficient to induce apoptosis in the hippocampal neuron cultures.ConclusionOur data suggest that translocation of FL-Bid is sufficient for the activation of mitochondrial cell death pathways in response to glutamate receptor overactivation.
- Subjects :
- Programmed cell death
Neurotoxins
Apoptosis
Mitochondrion
Caspase 8
Hippocampus
03 medical and health sciences
0302 clinical medicine
Animals
lcsh:QH573-671
Receptor
Cells, Cultured
Caspase
030304 developmental biology
Neurons
0303 health sciences
biology
lcsh:Cytology
Cell Biology
Molecular biology
Rats, Inbred F344
Rats
Cell biology
Protein Transport
Cytosol
Animals, Newborn
Receptors, Glutamate
biology.protein
NMDA receptor
Mutant Proteins
biological phenomena, cell phenomena, and immunity
030217 neurology & neurosurgery
BH3 Interacting Domain Death Agonist Protein
Peptide Hydrolases
Research Article
Subjects
Details
- ISSN :
- 14712121
- Volume :
- 8
- Database :
- OpenAIRE
- Journal :
- BMC Cell Biology
- Accession number :
- edsair.doi.dedup.....b559d98c97681ebdeec817a3890348ae