Pramipexole Inhibits MPP+-Induced Neurotoxicity by miR-494-3p/BDNF.

This study aimed to investigate the role of PPX in 1-Methyl-4-phenylpyridinium (MPP+)-treated neuroblastoma cells and explore the interaction between PPX and miR-494-3p/brain derived neurotrophic factor (BDNF) axis. SK-N-SH and CHP 212 cells challenged by MPP+ were used as cellular model of Parkinson's disease and incubated with PPX. The expression levels of miR-494-3p and BDNF were measured by quantitative real-time polymerase chain reaction or western blot. Neurotoxicity was investigated by cell apoptosis, inflammatory response and oxidative stress. The target association between miR-494-3p and BDNF was confirmed by luciferase reporter and RNA immunoprecipitation assays. miR-494-3p expression was increased and BDNF level was decreased in MPP+-treated SK-N-SH and CHP 212 cells, which were reversed by introduction of PPX. Pramipexole attenuated cell apoptosis, inflammatory response and oxidative stress in MPP+-treated SK-N-SH and CHP 212 cells. Knockdown of miR-494-3p also suppressed neurotoxicity induced by MPP+ in SK-N-SH and CHP 212 cells. BDNF was validated as a target of miR-494-3p and its silence abated the suppressive effect of miR-494-3p on MPP+-induced neurotoxicity. Moreover, addition of miR-494-3p and silence of BDNF mitigated the effect of PPX on MPP+-induced neurotoxicity. PPX inhibited MPP+-induced neurotoxicity in SK-N-SH and CHP 212 cells by decreasing miR-494-3p and increasing BDNF, indicating the potential therapeutic effect of PPX on Parkinson's disease. ...
Source: Neurochemical Research - Category: Neuroscience Authors: Tags: Neurochem Res Source Type: research