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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 orcid ; 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
; ; ; ; ; ; ; and
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
  • pmid:20850531
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
2016-04-04 07:42:37
date last changed
2022-03-23 01:31:44
@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          = {{https://lup.lub.lu.se/search/files/5149269/1692370.pdf}},
  doi          = {{10.1016/j.nbd.2010.09.005}},
  volume       = {{41}},
  year         = {{2011}},
}