Type

Journal Article

Authors

David C Henshall
Jochen H M Prehn
Andreas Strasser
Nikolaus Plesnila
Clara K Schindler
Aurelien Caballero-Caballero
Tobias Engel

Subjects

Biochemistry

Topics
cell death membrane proteins bcl 2 like protein 11 physiology subcellular fractions phenotype mice inbred c57bl bid3 protein mouse blotting western immunohistochemistry neuropeptides apoptosis inducing factor animals epilepsies partial mice metabolism hippocampus proto oncogene proteins seizures tumor suppressor proteins drug effects cell nucleus mice knockout apoptosis regulatory proteins genetics neurons biosynthesis pathology status epilepticus male puma protein mouse

BH3-only protein Bid is dispensable for seizure-induced neuronal death and the associated nuclear accumulation of apoptosis-inducing factor. (2010)

Abstract Prolonged seizures activate members of the Bcl-2 homology domain 3-only sub-group of the Bcl-2 protein family, which are essential for initiation of apoptosis signaling. Bid is a potent pro-apoptotic Bcl-2 homology domain 3-only protein, which upon proteolytic activation translocates to mitochondria to promote activation of the Bax/Bak sub-group of the pro-apoptotic Bcl-2 family and thereby contributes to release of apoptogenic molecules, such as cytochrome c and possibly apoptosis-inducing factor (AIF). Bid-deficient mice have been reported to show reduced lesion volumes after ischemia and trauma in vivo but a causal role for Bid in the setting of seizure-induced neuronal death has not been investigated. In this study, we studied Bid activation following status epilepticus in mice and compared hippocampal damage between wild-type and Bid-deficient animals. Full-length Bid was detected in normal mouse hippocampus and the cleaved (activated) p15 fragment of Bid was detected shortly after status epilepticus. Bid-deficient mice underwent equivalent electrographic seizure responses during status epilepticus as wild-type animals. Hippocampal counts of degenerating neurons and surviving neuron-specific nuclear protein-positive cells were not significantly different between wild-type and Bid-deficient mice. Additionally, nuclear translocation of AIF was not reduced in Bid-deficient compared with wild-type animals subjected to status epilepticus. The present study demonstrates that AIF is not dependent on Bid for mitochondrial release and nuclear import in this model and that while Bid is cleaved during seizure-induced neuronal death, it may be functionally redundant or even not essential.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

David C Henshall, Jochen H M Prehn, Andreas Strasser, Nikolaus Plesnila, Clara K Schindler, Aurelien Caballero-Caballero, Tobias Engel

Experts in our system

1
David C Henshall
Royal College of Surgeons in Ireland
Total Publications: 127
 
2
Jochen H M Prehn
Royal College of Surgeons in Ireland
Total Publications: 206
 
3
Andreas Strasser
Royal College of Surgeons in Ireland
Total Publications: 7
 
4
Nikolaus Plesnila
Royal College of Surgeons in Ireland
Total Publications: 9
 
5
Tobias Engel
Royal College of Surgeons in Ireland
Total Publications: 66