LC3-II may mediate ATR-induced mitophagy in dopaminergic neurons through SQSTM1/p62 pathway.

LC3-II may mediate ATR-induced mitophagy in dopaminergic neurons through SQSTM1/p62 pathway. Acta Biochim Biophys Sin (Shanghai). 2018 Aug 02;: Authors: Ma K, Wu H, Li P, Li B Abstract Atrazine (2-chloro-4-ethylamino-6-isopropylamine-1,3,5-triazine; ATR) has been demonstrated to regulate autophagy- and apoptosis-related proteins in doparminergic neuronal damage. In our study, we investigated the role of LC3-II in ATR-induced degeneration of dopaminergic neurons. In vivo dopaminergic neuron degeneration model was set up with ATR treatment and confirmed by the behavioral responses and pathological analysis. Dopaminergic neuron cells were transfected with LC3-II siRNA and treated with ATR to observe cell survival and reactive oxygen species release. The process of mitochondrial autophagy and the neurotoxic effects of mitochondrial autophagy were detected by immunofluorescence assay, immunohistochemical analysis, real-time PCR, and western blot analysis. Results showed that after ATR treatment, the grip strength of Wistar rats was significantly decreased, and behavioral signs of anxiety were clearly observed. The mRNA and protein levels of tyrosine hydroxylase, LC3-II, PINK1, and Parkin were significantly decreased in ATR-induced rat dopaminergic neurons and PC-12 cells, while the mRNA expression and protein levels of SQSTM1/p62 and Parl were increased. Exposure to ATR also led to accumulation of autophagic lysosomes and autophagic bodie...
Source: Acta Biochimica et Biophysica Sinica - Category: Biochemistry Authors: Tags: Acta Biochim Biophys Sin (Shanghai) Source Type: research