Rotenone-Induced Neurodegeneration Is Enabled by a p38-Parkin-ROS Signaling Feedback Loop.
J Agric Food Chem
; 69(46): 13942-13952, 2021 Nov 24.
Article
em En
| MEDLINE
| ID: mdl-34779196
ABSTRACT
Rotenone, a component of pesticides, is widely used in agriculture and potentially causes Parkinson's disease (PD). However, the regulatory mechanisms of rotenone-induced PD are unclear. Here, we revealed a novel feedback mechanism of p38-Parkin-ROS regulating rotenone-induced PD. Rotenone treatment led to not only the activation of p38 but also Parkin inactivation and reactive oxygen species (ROS) overproduction in SN4741 cells. Meanwhile, p38 activation regulated Parkin phosphorylation at serine 131 to disrupt Parkin-mediated mitophagy. Notably, both p38 inhibition and Parkin overexpression decreased ROS levels. Additionally, the ROS inhibitor N-acetyl-l-cysteine (NAC) inhibited p38 and activated Parkin-mediated mitophagy. Both p38 inhibition and the ROS inhibitor NAC exerted a protective effect by restoring cell death and mitochondrial function in rotenone-induced PD models. Based on these results, the p38-Parkin-ROS signaling pathway is involved in neurodegeneration. This pathway represents a valuable treatment strategy for rotenone-induced PD, and our study provides basic research evidence for the safe use of rotenone in agriculture.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Rotenona
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Espécies Reativas de Oxigênio
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Transtornos Parkinsonianos
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Ubiquitina-Proteína Ligases
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Proteínas Quinases p38 Ativadas por Mitógeno
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Inseticidas
Limite:
Animals
Idioma:
En
Revista:
J Agric Food Chem
Ano de publicação:
2021
Tipo de documento:
Article