| BH3-only protein Bid is dispensable for seizure-induced neuronal death and the associated nuclear accumulation of apoptosis-inducing factor. | |
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MedLine Citation:
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PMID: 20646170 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Tobias Engel; Aurelien Caballero-Caballero; Clara K Schindler; Nikolaus Plesnila; Andreas Strasser; Jochen H M Prehn; David C Henshall |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-07-30 |
Journal Detail:
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Title: Journal of neurochemistry Volume: 115 ISSN: 1471-4159 ISO Abbreviation: J. Neurochem. Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-09-15 Completed Date: 2010-10-13 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985190R Medline TA: J Neurochem Country: England |
Other Details:
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Languages: eng Pagination: 92-101 Citation Subset: IM |
Copyright Information:
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© 2010 The Authors. Journal Compilation © 2010 International Society for Neurochemistry. |
Affiliation:
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Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, Dublin 2, Ireland. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apoptosis Inducing Factor / metabolism* Apoptosis Regulatory Proteins / biosynthesis, genetics, physiology* Blotting, Western Cell Death / physiology* Cell Nucleus / metabolism* Epilepsies, Partial / pathology Hippocampus / pathology Immunohistochemistry Male Membrane Proteins / biosynthesis, genetics Mice Mice, Inbred C57BL Mice, Knockout Neurons / pathology* Neuropeptides / genetics, physiology* Phenotype Proto-Oncogene Proteins / biosynthesis, genetics Seizures / pathology* Status Epilepticus / pathology Subcellular Fractions / drug effects, metabolism Tumor Suppressor Proteins / biosynthesis, genetics |
| Chemical | |
Reg. No./Substance:
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0/Apoptosis Inducing Factor; 0/Apoptosis Regulatory Proteins; 0/Bcl-2-like protein 11; 0/Bid3 protein, mouse; 0/Membrane Proteins; 0/Neuropeptides; 0/PUMA protein, mouse; 0/Proto-Oncogene Proteins; 0/Tumor Suppressor Proteins |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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