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Apoptosis-inducing factor mediates dopaminergic cell death in response to lps-induced inflammatory stimulus Evidence in Parkinson's disease patients.

Burguillos Garcia, Miguel LU ; Hajji, N; Englund, E; Persson, A; Cenci Nilsson, Angela LU ; Machado, A; Cano, J; Joseph, B and Venero, J L (2011) In Neurobiology of Disease 41. p.177-188
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Neurobiology of Disease
volume
41
pages
177 - 188
publisher
Elsevier
external identifiers
  • wos:000285036400019
  • pmid:20850531
  • scopus:78349304719
ISSN
0969-9961
DOI
10.1016/j.nbd.2010.09.005
language
English
LU publication?
yes
id
e7bf7ebc-6d86-4bff-8025-2bfedfde3e22 (old id 1688072)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/20850531?dopt=Abstract
date added to LUP
2010-10-08 09:09:55
date last changed
2017-10-08 04:28:48
@article{e7bf7ebc-6d86-4bff-8025-2bfedfde3e22,
  abstract     = {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.},
  author       = {Burguillos Garcia, Miguel and Hajji, N and Englund, E and Persson, A and Cenci Nilsson, Angela and Machado, A and Cano, J and Joseph, B and Venero, J L},
  issn         = {0969-9961},
  language     = {eng},
  pages        = {177--188},
  publisher    = {Elsevier},
  series       = {Neurobiology of Disease},
  title        = {Apoptosis-inducing factor mediates dopaminergic cell death in response to lps-induced inflammatory stimulus Evidence in Parkinson's disease patients.},
  url          = {http://dx.doi.org/10.1016/j.nbd.2010.09.005},
  volume       = {41},
  year         = {2011},
}