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BMC Cell Biol. 2007 Feb 27;8:7.

Full length Bid is sufficient to induce apoptosis of cultured rat hippocampal neurons.

Author information

1
Department of Physiology and RCSI Neuroscience Research Centre, Royal College of Surgeons in Ireland, Dublin 2, Ireland. hgkoenig@rcsi.ie <hgkoenig@rcsi.ie>

Abstract

BACKGROUND:

Bcl-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 microM).

RESULTS:

Western 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.

CONCLUSION:

Our data suggest that translocation of FL-Bid is sufficient for the activation of mitochondrial cell death pathways in response to glutamate receptor overactivation.

PMID:
17326836
PMCID:
PMC1808451
DOI:
10.1186/1471-2121-8-7
[Indexed for MEDLINE]
Free PMC Article

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