Autophagy Stimulation Decreases Dopaminergic Neuronal Death Mediated by Oxidative Stress

被引:27
作者
Ramirez-Moreno, Marcela J. [1 ]
Duarte-Jurado, Ana P. [1 ]
Gopar-Cuevas, Yareth [1 ]
Gonzalez-Alcocer, Alfredo [1 ]
Loera-Arias, Maria J. [1 ]
Saucedo-Cardenas, Odila [1 ,2 ]
Montes de Oca-Luna, Roberto [1 ]
Rodriguez-Rocha, Humberto [1 ]
Garcia-Garcia, Aracely [1 ]
机构
[1] Univ Autonoma Nuevo Leon, Fac Med, Dept Histol, Francisco I Madero S-N, Monterrey 64460, Nuevo Leon, Mexico
[2] Inst Mexicano Seguro Social, Ctr Invest Biomed Noreste, Dept Mol Genet, Delegacion, Nuevo Leon, Mexico
关键词
Autophagy; Oxidative stress; Paraquat; Parkinson's disease; Rapamycin; PARKINSONS-DISEASE; CELL-DEATH; MICROGLIAL ACTIVATION; ALPHA-SYNUCLEIN; RAPAMYCIN PROTECTS; RAT MODEL; PARAQUAT; APOPTOSIS; PATHWAYS; PHOSPHATIDYLSERINE;
D O I
10.1007/s12035-019-01654-1
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The neurodegenerative process of Parkinson's disease (PD) involves autophagy impairment and oxidative stress. Therefore, we wanted to determine whether stimulation of autophagy protects dopaminergic cell death induced by oxidative stress in a PD model. Since environmental exposure to herbicides increases the risk to develop PD, the experimental model was established using the herbicide paraquat, which induces autophagy disruption, oxidative stress, and cell death. Rapamycin-stimulated autophagy inhibited calpain-dependent and independent apoptosis induced by paraquat. Autophagy stimulation decreased oxidative stress and peroxiredoxins (PRXs) hyperoxidation induced by paraquat. Cells exposed to paraquat displayed abnormally large autophagosomes enclosing mitochondria, which correlates with an increase of p62, an essential mitophagy regulator. Interestingly, when autophagy was stimulated before paraquat treatment, autophagosome size and number were similar to that observed in control cells. Motor and cognitive function impairment induced by paraquat showed an improvement when preceded by autophagy stimulation. Importantly, dopaminergic neuronal death and microglial activation mediated by paraquat were significantly reduced by rapamycin-induced autophagy. Our results indicate that autophagy stimulation has a protective effect on dopaminergic neurons and may have a promising potential to prevent or delay PD progression.
引用
收藏
页码:8136 / 8156
页数:21
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