Apoptosis-inducing factor mediates dopaminergic cell death in response to lps-induced inflammatory stimulus Evidence in Parkinson's disease patients.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1688072
- author
- Burguillos Garcia, Miguel LU ; Hajji, N ; Englund, E ; Persson, A ; Cenci Nilsson, Angela LU ; Machado, A ; Cano, J ; Joseph, B and Venero, J L
- organization
- publishing date
- 2011
- 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}}, }