Downregulation of miR‑21 suppresses 1‑methyl‑4‑phenylpyridinium‑induced neuronal damage in MES23.5 cells

• Published in: Experimental and therapeutic medicine 2019-10, Vol.18 (4), p.2467-2474
• Main Authors: Mao, Huawu, Ding, Lidong
• Format: Article
• Language: English
• Subjects: Analysis; Apoptosis; Hydroxylases; Interleukins; Luciferase; MicroRNA; MicroRNAs; Necrosis; Neurons; Neurotoxicity; Novels; Oxidative stress; Parkinson's disease; Pathogenesis; Phenols (Class of compounds); Polymerase chain reaction; Proteins; Reactive oxygen species; Scientific equipment industry; Studies; Tumors; Tyrosine
• ISSN: 1792-0981; 1792-1015
• DOI: 10.3892/etm.2019.7853

Accumulating evidence suggests that overproduction of oxidative stress, increases neuroinflammation and activates apoptosis. These two processes are associated with the development of Parkinson's disease (PD). The present study aimed to investigate the role of miR-21 in the development of PD. 1-Methyl-4-phenylpyridinium ([MPP.sup.+]) was used to induce a PD-like model in MES23.5 cells. The results of the reverse transcription-quantitative PCR assays indicated that miR-21 levels were markedly increased in MES23.5 cells following [MPP.sup.+] treatment. Furthermore, MES23.5 cells were transfected with miR-21 inhibitor, mimics and/ or relevant negative control, following [MPP.sup.+] administration. The results of the functional assays revealed that downregulation of miR-21 significantly attenuated the induction of cell apoptosis and reactive oxygen species (ROS) production, while it enhanced the survival of [MPP.sup.+]-induced MES23.5 cells. Furthermore, downregulation of miR-21 increased the expression levels of tyrosine hydroxylase, whereas suppression of miR-21 inhibited the production of pro-inflammatory cytokines [interleukin (IL)-6, IL-1[beta] and tumor necrosis factor-[alpha]] in MES23.5 cells. Western blot analysis further indicated that the Bcl-2/Bax protein expression ratio was significantly increased and double luciferase assay analysis confirmed that Bcl-2 was a direct target of miR-21. Taken collectively, the data demonstrated that downregulation of miR-21 protected cells from [MPP.sup.+]-mediated cytotoxicity by the inhibition of apoptosis induction, the reduction of the inflammatory response and the suppression of ROS production. The present findings may provide novel approaches for PD clinical treatment. Key words: microRNA-21, Parkinson's disease, 1-methyl-4-phenylpyridinium, MES23.5