Peer Reviewed

1

Document Type

Article

Publication Date

27-2-2007

Keywords

Animals, Animals, Newborn, Apoptosis, BH3 Interacting Domain Death Agonist Protein, Caspase 8, Cells, Cultured, Hippocampus, Mutant Proteins, Neurons, Neurotoxins, Peptide Hydrolases, Protein Transport, Rats, Rats, Inbred F344, Receptors, Glutamate

Comments

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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.

Disciplines

Physics | Physiology

Citation

König HG, Rehm M, Gudorf D, Krajewski S, Gross A, Ward MW, Prehn JH. Full length Bid is sufficient to induce apoptosis of cultured rat hippocampal neurons. BMC Cell Biology. 2007;8:7.

PubMed ID

17326836

DOI Link

10.1186/1471-2121-8-7

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