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

Abstract

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 + ) 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 + treatment. Furthermore, MES23.5 cells were transfected with miR-21 inhibitor, mimics and/ or relevant negative control, following MPP + 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 + -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-1β and tumor necrosis factor-α] 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 + -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.

miR-21-5p Under-Expression in Patients with Obstructive Sleep Apnea Modulates Intermittent Hypoxia with Re-Oxygenation-Induced-Cell Apoptosis and Cytotoxicity by Targeting Pro-Inflammatory TNF-α-TLR4 Signaling

“…Furthermore, miR-21 could prevent human neural stem cell injury induced by oxygen and glucose deprivation through PDCD4/caspase-3 pathway [33,34]. In contrast, miR-21 over-expression was associated with right ventricle dysfunction in patients with hypoxia-induced pulmonary hypertension, and promoted neuronal damage in vitro [26,35]. In the present study, we found decreased miR-21-5p gene expressions both in severe OSA patients and in response to IHR stimuli.…”

MicroRNA-6862 inhibition elevates sphingosine kinase 1 and protects neuronal cells from MPP+-induced apoptosis

“…In addition, miR-7 downregulated RelA, a member of the nuclear factor κB (NF-κB) family of transcription factors, and augmented neuronal glucose transporter 3 (Glut3) to promote glycolysis in SH-SY5Y cells and ReNcell VM cells [ 34 ]. Mao et al, found that miR-21 downregulation was able to attenuate MPP + -induced MES23.5 cell death by apoptosis inhibition and reactive oxygen species (ROS) scavenging [ 35 ]. In SH-SY5Y cells and primary dopaminergic neurons, astrocyte-derived exosomal miR-200a-3p downregulated MKK4 (mitogen-activated protein kinase kinase 4) and prevented MPP + -induced apoptotic cell death [ 36 ].…”

MicroRNA-21 Is a Versatile Regulator and Potential Treatment Target in Central Nervous System Disorders

“…miR-21 levels were markedly increased in MES cells following 1-methyl-4-phenylpyridinium (MPP + ) treatment. Downregulation of miR-21 could reduce the MPP + -mediated cytotoxicity via inhibition of apoptosis and inflammatory responses in MES cells, which provides a novel approach to PD treatment (Mao and Ding, 2019). Su et al (2016) showed that the level of miR-21 was significantly increased in PD cells and mouse models.…”