Abstract
Parkinson's disease (PD) is a leading cause of disability. Long noncoding RNA (LncRNA) OIP5-AS1 alleviates the accumulation and toxicity of 1-methyl-4-phenylpyridine (MPP+ )/-induced α-synuclein in human neuroblastoma SH-SY5Y cells, which may be involved in the pathological process of PD. This study explored the neuroprotective effect of lncRNA OIP5-AS1 on MPP+ /-induced SH-SY5Y cell model of PD, so as to provide a theoretical basis for PD treatment. The PD cell model was established (MPP+ group). The overexpression vector oe-OIP5-AS1 was constructed and transfected into MPP+/-induced SH-SY5Y cells, which were further transfected with miR-137 mimic or si-NIX plasmids. The localization of OIP5-AS1 and its binding sites with miR-137 were predicted by subcellular isolation and fluorescence in situ hybridization analysis. The targeting relationships between OIP5-AS1 and miR-137, and miR-137 and NIX were detected by dual-luciferase reporter assays. The mitochondrial membrane potential (Δψm) and total reactive oxygen species (ROS) levels, and expressions of α-synuclein, inflammatory cytokines, and microglia-activated chemokines, cell activity, and apoptosis were assessed. OIP5-AS1 was downregulated in MPP+ cells. After OIP5-AS1 overexpression, miR-137 was downregulated and NIX was upregulated in MPP+ cells, inflammatory factors and chemokines were downregulated. There were target relationships between OIP5-AS1 and miR-137, and miR-137 and NIX. After OIP5-AS1 overexpression, miR-137 overexpression or NIX downregulation inhibited mitochondrial autophagy and ROS levels and aggravated mitochondrial vacuolation; and partially reversed the effect of OIP5-AS1 overexpression on promoting mitochondrial autophagy and protection on MPP+ cells. Collectively, lncRNA OIP5-AS1 promoted NIX expression through competitively binding to miR-137, and promoted mitochondrial autophagy, thus protecting neurons from degeneration which might be seen in patients with PD.