Bookmark
Forward
JWA antagonizes paraquat-induced neurotoxicity via activation of Nrf2.
X Zhao, R Wang, J Xiong, D Yan, A Li, S Wang, J Xu, J Zhou
Toxicology letters 2017 Aug 05
Sizes of these terms reflect their relevance to your search.
Paraquat (PQ), a widely used environmental toxin in agriculture, contributes to the onset and progression of Parkinson's disease (PD) by damaging neurons. The JWA gene, also known as ARL6IP5, exerts a protective effect on degenerating dopamine (DA) neurons. However, the roles of JWA in PQ-induced neuronal damage are still unknown. In our study, two neuronal cell lines (HT-22 and SH-SY5Y) and neuron-specific JWA knockout (JWA-nKO) and age-matched wild-type (JWA-nWT) mice were subjected to PQ treatment. The results indicate that PQ administration triggers the upregulation of JWA. Elevated expression of JWA rescues the accumulation of reactive oxygen species (ROS) while increasing glutathione (GSH) and glutathione peroxidase (GPx) levels under PQ exposure. Further investigations revealed that the protective effect of JWA mostly involves regulation of the MEK/PI3K-Nrf2 axis. Our results suggest that JWA may be a novel target for the prevention and treatment of PQ-induced PD. Copyright © 2017. Published by Elsevier B.V.
Citation
X Zhao, R Wang, J Xiong, D Yan, A Li, S Wang, J Xu, J Zhou.
JWA antagonizes paraquat-induced neurotoxicity via activation of Nrf2.
Toxicology letters.
2017 Aug 05;277:32-40
Mesh Tags
Animals
Apoptosis
Behavior, Animal
Carrier Proteins
Cell Line, Tumor
Dose-Response Relationship, Drug
Extracellular Signal-Regulated MAP Kinases
Glutathione
Glutathione Peroxidase
HEK293 Cells
Heat-Shock Proteins
Herbicides
Humans
Inhibitory Concentration 50
Intracellular Signaling Peptides and Proteins
MAP Kinase Kinase Kinases
Mice, Knockout
Motor Activity
NF-E2-Related Factor 2
Neurons
Neurotoxicity Syndromes
Oxidative Stress
Paraquat
Phosphatidylinositol 3-Kinase
Proto-Oncogene Proteins c-akt
Reactive Oxygen Species
Signal Transduction
Transcription, Genetic
Transcriptional Activation
Transfection
Substances
ARL6IP5 protein, human
Arl6ip5 protein, mouse
Carrier Proteins
Heat-Shock Proteins
Herbicides
Intracellular Signaling Peptides and Proteins
NF-E2-Related Factor 2
NFE2L2 protein, human
Reactive Oxygen Species
Glutathione Peroxidase
Phosphatidylinositol 3-Kinase
Proto-Oncogene Proteins c-akt
Extracellular Signal-Regulated MAP Kinases
MAP Kinase Kinase Kinases
Glutathione
Paraquat
PMID: 28428137
View Full Text