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

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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; Hajji, N; Englund, E; Persson, A; Cenci Nilsson, Angela; Machado, A; Cano, J; Joseph, B; Venero, J L.

In: Neurobiology of Disease, Vol. 41, 2011, p. 177-188.

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Burguillos Garcia, Miguel ; Hajji, N ; Englund, E ; Persson, A ; Cenci Nilsson, Angela ; Machado, A ; Cano, J ; Joseph, B ; Venero, J L. / Apoptosis-inducing factor mediates dopaminergic cell death in response to lps-induced inflammatory stimulus Evidence in Parkinson's disease patients. In: Neurobiology of Disease. 2011 ; Vol. 41. pp. 177-188.

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TY - JOUR

T1 - Apoptosis-inducing factor mediates dopaminergic cell death in response to lps-induced inflammatory stimulus Evidence in Parkinson's disease patients.

AU - Burguillos Garcia, Miguel

AU - Hajji, N

AU - Englund, E

AU - Persson, A

AU - Cenci Nilsson, Angela

AU - Machado, A

AU - Cano, J

AU - Joseph, B

AU - Venero, J L

PY - 2011

Y1 - 2011

N2 - 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.

AB - 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.

U2 - 10.1016/j.nbd.2010.09.005

DO - 10.1016/j.nbd.2010.09.005

M3 - Article

VL - 41

SP - 177

EP - 188

JO - Neurobiology of Disease

T2 - Neurobiology of Disease

JF - Neurobiology of Disease

SN - 0969-9961

ER -