title: MicroRNA-181a Regulates Apoptosis and Autophagy Process in Parkinson's Disease by Inhibiting p38 Mitogen-Activated Protein Kinase (MAPK)/c-Jun N-Terminal Kinases (JNK) Signaling Pathways.
abstract: BACKGROUND microRNA (miR)-181a has been reported to be downregulated in Parkinson's disease (PD), but the regulatory mechanism of miR-181a on neuron apoptosis and autophagy is still poorly understood. We aimed to investigate the neuroprotective effects of miR-181a on PD in vitro. MATERIAL AND METHODS Human SK-N-SH neuroblastoma cells were incubated with different concentrations of 1-methyl-4-phenylpyridinium ion (MPP+) to induce the PD model. The expression of miR-181a was then analyzed. After transfection with miR-181a mimic or scramble following MPP+ treatment, the expression of autophagy protein markers (LC3II, LC3I, and Beclin 1) and p38 mitogen-activated protein kinase (MAPK)/c-Jun N-terminal kinases (JNK) signaling proteins (p-p38, p38, p-JNK, and JNK) and cell apoptosis were detected. Furthermore, the cells were transfected with miR-181a inhibitor and cultured in the presence or absence of p38 inhibitor SB203582 or JNK inhibitor SP600125, and the cell apoptosis was tested again. RESULTS The expression of miR-181a was gradually decreased with the increase of MPP+ concentration (P<0.05, P<0.01, or P<0.001). Overexpression of miR-181a significantly decreased the LC3II/LC3I ratio, Beclin 1 expression, cell apoptosis, and the expression of p-p38 and p-JNK compared to the MPP+ + miR-181a scramble group (all P<0.05). In addition, we observed that SB203582 or SP600125 showed no effects on cell apoptosis, but the effects of miR-181a inhibitor on cell apoptosis were reversed by administration of SB203582 or SP600125 compared to the scramble group (P<0.05). CONCLUSIONS Our results suggest that miR-181a regulates apoptosis and autophagy in PD by inhibiting the p38 MAPK/JNK pathway.
authors.affiliation: Department of Internal Medicine Neurology, HuaMei Branch of the 2nd People's Hospital of Liaocheng, Liaocheng, Shandong, China (mainland).
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Internal Medicine Neurology, HuaMei Branch of the 2nd People's Hospital of Liaocheng, Liaocheng, Shandong, China (mainland).
authors.forename: Yanfeng
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Internal Medicine Neurology, HuaMei Branch of the 2nd People's Hospital of Liaocheng, Liaocheng, Shandong, China (mainland).
authors.forename: Xiaotun
authors.initials: X
authors.lastname: Zhu
mesh_terms: D017209:Apoptosis / Q000235:genetics; D001343:Autophagy / Q000235:genetics; D045744:Cell Line, Tumor; D015536:Down-Regulation; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000235:genetics*; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009447:Neuroblastoma; D009474:Neurons / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D010300:Parkinson Disease / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: C540193:MIrn181 microRNA, human; D035683:MicroRNAs; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases