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The role of protein kinase C alpha in tri‐ortho‐cresyl phosphate‐induced autophagy in human neuroblastoma SK‐N‐SH cells
Author(s) -
Deng Qiang,
Jiang Lan,
Mao Liang,
Song XiaoHua,
He ChuQi,
Li XiaoLing,
Zhang ZhaoHui,
Zeng HuaiCai,
Chen Jiaxiang,
Long DingXin
Publication year - 2020
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.3999
Subject(s) - autophagy , neuroblastoma , chemistry , alpha (finance) , phosphate , kinase , protein kinase a , cancer research , endocrinology , medicine , biochemistry , biology , cell culture , apoptosis , construct validity , nursing , patient satisfaction , genetics
As an organophosphorus ester, tri‐ortho‐cresyl phosphate (TOCP) has been widely used in agriculture and industry. It is reported that TOCP can induce organophosphate‐induced delayed neuropathy (OPIDN) in sensitive animal and human species. However, the exact molecular mechanisms underlying TOCP‐induced neurotoxicity are still unknown. In this study, we found that TOCP could induce autophagy by activating protein kinase C alpha (PKCα) signaling in neuroblastoma SK‐N‐SH cells. PKCα activators could positively regulate TOCP‐induced autophagy by increasing the expression levels of neighbor BRCA1 gene protein 1 (NBR1), LC3 and P62 autophagic receptor protein. Furthermore, PKCα activation impaired the ubiquitin‐proteasome system (UPS), resulting in inhibition of proteasome activity and accumulation of ubiquitinated proteins. UPS dysfunction could stimulate autophagy to serve as a compensatory pathway, which contributed to the accumulation of the abnormally hyperphosphorylated tau proteins and degradation of impaired proteins of the MAP 2 and NF‐H families in neurodegenerative disorders.