| Apoptosis-inducing factor mediates dopaminergic cell death in response to LPS-induced inflammatory stimulus: evidence in Parkinson's disease patients. | |
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MedLine Citation:
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PMID: 20850531 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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We show that intranigral lipopolysaccharide (LPS) injection, which provokes specific degeneration of DA neurons, induced caspase-3 activation in the rat ventral mesencephalon, which was mostly associated with glial cells. In contrast, nigral DA neurons exhibited AIF nuclear translocation in response to LPS. A significant decrease of the Bcl-2/Bax ratio in nigral tissue after LPS injection was observed. We next developed an in vitro co-culture system with the microglial BV2 and the DA neuronal MN9D murine cell lines. The silencing of caspase-3 or AIF by small interfering RNAs exclusively in the DA MN9D cells demonstrated the key role of AIF in the LPS-induced death of DA cells. In vivo chemical inhibition of caspases and poly(ADP-ribose)polymerase-1, an upstream regulator of AIF release and calpain, proved the central role of the AIF-dependent pathway in LPS-induced nigral DA cell death. We also observed nuclear translocation of AIF in the ventral mesencephalon of Parkinson's disease subjects. |
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Authors:
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M A Burguillos; N Hajji; E Englund; A Persson; A M Cenci; A Machado; J Cano; B Joseph; J L Venero |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-09-17 |
Journal Detail:
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Title: Neurobiology of disease Volume: 41 ISSN: 1095-953X ISO Abbreviation: Neurobiol. Dis. Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2010-11-16 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9500169 Medline TA: Neurobiol Dis Country: United States |
Other Details:
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Languages: eng Pagination: 177-88 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Elsevier Inc. All rights reserved. |
Affiliation:
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Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad de Sevilla, Spain. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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