Type

Other / n/a

Authors

Jochen HM Prehn
Manus W Ward
Atan Gross
Stan Krajewski
Daniel Gudorf
Markus Rehm
Hans Georg König

Subjects

Biochemistry

Topics
animals apoptosis hippocampus bh3 interacting domain death agonist protein physics cells cultured neurons neurotoxins cells receptors peptide hydrolases protein transport newborn animals newborn caspase 8 mutant proteins inbred f344 physiology receptors glutamate rats inbred f344 rats cultured glutamate

Full length Bid is sufficient to induce apoptosis of cultured rat hippocampal neurons. (2007)

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.
Collections Ireland -> Royal College of Surgeons in Ireland -> Physiology and Medical Physics Articles
Ireland -> Royal College of Surgeons in Ireland -> Department of Physiology and Medical Physics

Full list of authors on original publication

Jochen HM Prehn, Manus W Ward, Atan Gross, Stan Krajewski, Daniel Gudorf, Markus Rehm, Hans Georg König

Experts in our system

1
Jochen H M Prehn
Royal College of Surgeons in Ireland
Total Publications: 206
 
2
Markus Rehm
Royal College of Surgeons in Ireland
Total Publications: 55
 
3
Hans Georg König
Royal College of Surgeons in Ireland
Total Publications: 22