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• W2945408990 abstract "Tri-ortho-cresyl phosphate (TOCP) is a typical organophosphorus compound that can cause organophosphate-induced delayed neuropathy (OPIDN), which is pathologically characterized by axonal degeneration. Nowadays, mitochondrial dysfunction is regarded as a potential mechanism contributing to OPIDN progress. Mitophagy, a selective type of autophagy, is required to segregate damaged mitochondria from healthy mitochondrial networks and deliver them to lysosome for degradation. This research was designed to investigate the role of mitophagy in axon degeneration following TOCP administration in an in vitro model. Differentiated neuro2a (N2a) cells were divided into four groups and treated with 0, 5, 10, and 20 μM TOCP for 24 h, respectively. The critical proteins in PINK1-Parkin-dependent mitophagy including LC3, P62, PINK1, Parkin, mitochondrial proteins, and autophagic receptors were detected by immunoblotting and immunofluorescence. After TOCP treatment, increased level of ROS in N2a cells revealed a significant mitochondria damage. Meanwhile, it was observed that much more PINK1, Parkin, and LC3-II were translocated to the mitochondria. Furthermore, immunofluorescence analysis demonstrated that the co-localization of Parkin and LC3 was significantly increased. These results suggested that PINK1-Parkin dependent mitophagy pathway in N2a cells was activated by TOCP treatment. In addition, P62, a major autophagic receptor, was markedly accumulated on the mitochondria, which indicated that P62 might play a critical role in facilitating mitophagy under TOCP-induced axonal degeneration. Taken together, our results suggest that TOCP exposure resulted in the activation of PINK1-Parkin-dependent mitophagy in N2a cells. Mitophagy may act as a positively reactive mode in eliminating dysfunctional mitochondria and therefore protect neurons against TOCP neurotoxicity." @default.
• W2945408990 created "2019-05-29" @default.
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• W2945408990 date "2019-08-01" @default.
• W2945408990 modified "2023-10-18" @default.
• W2945408990 title "Activation of PINK1-Parkin-dependent mitophagy in Tri-ortho-cresyl phosphate-treated Neuro2a cells" @default.
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• W2945408990 doi "https://doi.org/10.1016/j.cbi.2019.05.025" @default.
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