Upregulation of miR-200a and miR-204 in MPP + -treated differentiated PC12 cells as a model of Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is ranked as the second most common neurodegenerative disorder caused by loss of dopaminergic neurons in the substantia nigra. Micro(mi)RNAs are a class of small noncoding RNAs that regulate gene expression and aberrant expression of them is closely correlated with many neurodegenerative conditions including PD. Silent information regulator 1 (SIRT1) as a known deacetylase and B-cell lymphoma-2 (BCL2) as an antiapoptotic factor play vital roles in neural protection and survival.

METHODS: Differentiated PC12 cells exposed to MPP+ were served here as a known PD model. Cell viability was determined by MTS assay. Apoptotic cells and ROS levels were detected using flow cytometry. Gene selection and miRNA-mRNA interaction analysis were performed through in silico methods. Relative expression of miRNAs and genes was examined by RT-qPCR.

RESULTS: MPP+ exposure markedly reduced cell viability, enhanced oxidative stress, and induced apoptosis in differentiated PC12 cells. Sirt1 and BCL2were shown to be markedly declined in response to MPP+ , while miR-200a and miR-204 were significantly upregulated.

CONCLUSION: The first novel finding of the current study is altered expression of miR-200a and miR-204 in differentiated PC12 cells in response to MPP+ , suggesting that deregulation of them participate in MPP+ neurotoxicity mechanisms, possibly via affecting the expression of Sirt1 and BCL2 as potential targets.