| Bcl-2 homology domain 3-only proteins Puma and Bim mediate the vulnerability of CA1 hippocampal neurons to proteasome inhibition in vivo. | |
| | |
MedLine Citation:
|
PMID: 21198986 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
|
Bcl-2 homology domain 3 (BH3)-only proteins are pro-apoptotic Bcl-2 family members that play important roles in upstream cell death signalling during apoptosis. Proteasomal stress has been shown to contribute to the pathology of cerebral ischaemia and many neurodegenerative disorders. Here we explored the contribution of BH3-only proteins in mediating proteasome-inhibition-induced apoptosis in the murine brain in vivo. Stereotactic intrahippocampal microinjection of the selective proteasome inhibitor epoxomicin (2.5 nmol) induced a delayed apoptosis within only the CA1 hippocampal neurons and not neurons within the CA3 or dentate gyrus regions, a selective vulnerability similar to that seen during ischaemia. This injury developed over a time-course of 3 days and was characterized by positive terminal deoxynucleotidyl transferase dUTP nick end labelling staining and nuclear condensation. Previous work from our laboratory has identified the BH3-only protein p53-upregulated mediator of apoptosis (Puma) as mediating proteasome-inhibition-induced apoptosis in cultured neural cells. Genetic deletion of puma reduced the number of terminal deoxynucleotidyl transferase dUTP nick end labelling-positive cells within the CA1 following epoxomicin microinjection but it did not provide a complete protection. Subsequent studies identified the BH3-only protein Bim as also being upregulated during proteasome inhibition in organotypic hippocampal slice cultures and after epoxomicin treatment in vivo. Interestingly, the genetic deletion of bim also afforded significant neuroprotection, although this protection was less pronounced. In summary, we demonstrate that the BH3-only proteins Puma and Bim mediate the delayed apoptosis of CA1 hippocampal neurons induced by proteasome inhibition in vivo, and that either BH3-only protein can only partly compensate for the deficiency of the other. |
| | |
Authors:
|
Takuro Tsuchiya; Helena P Bonner; Tobias Engel; Ina Woods; Satoshi Matsushima; Manus W Ward; Waro Taki; David C Henshall; Caoimhín G Concannon; Jochen H M Prehn |
Related Documents
:
|
11955606 - Possible inflammatory mediators in tympanosclerosis development. 19828096 - Anti-inflammatory properties of the plant verbascum mallophorum. 11316326 - Melatonin protects against streptozotocin, but not interleukin-1beta-induced damage of ... 17112236 - Mutagenesis of the supf gene of psp189 replicating in ad293 cells cocultivated with act... 12779456 - Bistability in cell signaling: how to make continuous processes discontinuous, and reve... 22235106 - Drivers of oxidative stress in acute pancreatitis: the role of nutrition therapy. |
Publication Detail:
|
Type: Journal Article Date: 2010-12-31 |
Journal Detail:
|
Title: The European journal of neuroscience Volume: 33 ISSN: 1460-9568 ISO Abbreviation: Eur. J. Neurosci. Publication Date: 2011 Feb |
Date Detail:
|
Created Date: 2011-01-31 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 8918110 Medline TA: Eur J Neurosci Country: France |
Other Details:
|
Languages: eng Pagination: 401-8 Citation Subset: IM |
Copyright Information:
|
© 2010 The Authors. European Journal of Neuroscience © 2010 Federation of European Neuroscience Societies and Blackwell Publishing Ltd. |
Affiliation:
|
Department of Physiology and Medical Physics and RCSI Neuroscience Research Centre, Royal College of Surgeons in Ireland, 123 St Stephen's Green, Dublin 2, Ireland Department of Neurosurgery, Mie University School of Medicine, Tsu, Mie, Japan. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Cholinergic and non-cholinergic mesopontine tegmental neurons projecting to the subthalamic nucleus ...
Next Document: Development of monotonic neuronal tuning in the monkey inferotemporal cortex through long-term learn...