Article
Apoptosis-inducing factor mediates dopaminergic cell death in response to LPS-induced inflammatory stimulus: Evidence in Parkinson's disease patients
Author/s | Burguillos García, Miguel Ángel
Hajji, Nabil Englund, Elisabet Persson, Annette Cenci, Maria Angela Machado, Alberto Cano, Josefina Joseph, Bertrand Venero Recio, José Luis ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
Department | Universidad de Sevilla. Departamento de Bioquímica y Biología Molecular |
Publication Date | 2011-01 |
Deposit Date | 2023-07-07 |
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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. ... 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. © 2010 Elsevier Inc. |
Funding agencies | Ministerio de Ciencia Y Tecnología (MCYT). España |
Project ID. | SAF 2006-04119
![]() SAF 2009-13778 (JLV) ![]() |
Citation | Burguillos García, M.Á., Hajji, N., Englund, E., Persson, A., Cenci, M.A., Machado, A.,...,Venero Recio, J.L. (2011). Apoptosis-inducing factor mediates dopaminergic cell death in response to LPS-induced inflammatory stimulus: Evidence in Parkinson's disease patients. Neurobiology of Disease, 41 (1), 177-188. https://doi.org/10.1016/j.nbd.2010.09.005. |
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