02 February 2020 : Laboratory Research
Downregulation of MiR-218-5p Protects Against Oxygen-Glucose Deprivation/Reperfusion-Induced Injuries of PC12 Cells via Upregulating N-myc Downstream Regulated Gene 4 (NDRG4)
Huiying Zhu1BE, Xiaojing Wang2CF, Shaoyuan Chen2AG*DOI: 10.12659/MSM.920101
Med Sci Monit 2020; 26:e920101
Abstract
BACKGROUND: Cerebral ischemia is a major player of acute ischemic stroke (AIS) and mainly caused by blood vessels obstruction-induced reduced blood flow. Furthermore, miR-218-5p level was elevated in patients with AIS compared with controls. The present study investigated the biochemical mechanisms underlying the role of miR-218-5p in AIS in vitro.
MATERIAL AND METHODS: PC12 cells were chosen to establish oxidative-glucose deprivation/re-oxygenation (OGD/R) injury model. The interaction between miR-218-5p and N-myc downstream regulated gene 4 (NDRG4) was evaluated by Luciferase reporter assay. The levels of NDRG4, endothelial nitric oxide synthase (eNOS) and protein related to cell apoptosis were quantitatively analyzed with real-time quantitative polymerase chain reaction (RT-qPCR) or western blotting. Inflammatory cytokines, myeloperoxidase (MPO) and oxidative stress status were measured using specific commercial assay kits. Further, the cells apoptosis was analyzed with flow cytometry assay.
RESULTS: MiR-218-5p level was notably increased in OGD/R injured PC12 cells and directly targeted NDRG4. MiR-218-5p inhibitor significantly inhibited inflammatory cytokines release, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and monocyte chemotactic protein 1 (MCP-1). In addition, miR-218-5p downregulation ameliorated nitric oxide (NO) and eNOS levels and suppressed the inducible nitric oxide synthase (iNOS) expression and cell apoptosis. However, NDRG4 silencing abolished all corrective effects of miR-218-5p inhibitor in OGD/R injured PC12 cells.
CONCLUSIONS: Downregulation of miR-218-5p protect against OGDR-induced injuries of PC12 cells through reducing inflammatory cytokines secretion, oxidative stress status, apoptosis rate and maintenance of endovascular homeostasis via upregulating NDRG4. MiR-218-5p may serve as a novel effective biomarker to monitor AIS progression.
Keywords: Encephalitis, Hypoxia-Ischemia, Brain, Culture Media, Down-Regulation, Glucose, ischemic stroke, Nerve Tissue Proteins, Oxygen
Editorial
01 January 2026 : Editorial
Editorial: Increasing Awareness of Lung Cancer in Non-Smokers and Never-Smokers Challenges Current Approaches to Prevention and Screening
DOI: 10.12659/MSM.952454
Med Sci Monit 2026; 32:e952454
In Press
Clinical Research
Institutional and Regional Variations in Access to Clinical Trials and Next-Generation Sequencing in Turkis...Med Sci Monit In Press; DOI: 10.12659/MSM.951027
Clinical Research
Low-Intensity Blood Flow-Restricted Multi-Joint Exercise Improves Muscle Function in Patients With Patellof...Med Sci Monit In Press; DOI: 10.12659/MSM.950516
Review article
Musculoskeletal Ultrasound and MRI in the Evaluation of Chemotherapy-Induced Peripheral Neuropathy: A ReviewMed Sci Monit In Press; DOI: 10.12659/MSM.951283
Clinical Research
Sensory Processing, Dissociation, and Affective Symptoms in Misophonia: A Cross-Sectional Study of 35 AdultsMed Sci Monit In Press; DOI: 10.12659/MSM.950938
Most Viewed Current Articles
17 Jan 2024 : Review article 10,187,196
Vaccination Guidelines for Pregnant Women: Addressing COVID-19 and the Omicron VariantDOI :10.12659/MSM.942799
Med Sci Monit 2024; 30:e942799
13 Nov 2021 : Clinical Research 3,708,487
Acceptance of COVID-19 Vaccination and Its Associated Factors Among Cancer Patients Attending the Oncology ...DOI :10.12659/MSM.932788
Med Sci Monit 2021; 27:e932788
14 Dec 2022 : Clinical Research 2,341,643
Prevalence and Variability of Allergen-Specific Immunoglobulin E in Patients with Elevated Tryptase LevelsDOI :10.12659/MSM.937990
Med Sci Monit 2022; 28:e937990
16 May 2023 : Clinical Research 706,524
Electrophysiological Testing for an Auditory Processing Disorder and Reading Performance in 54 School Stude...DOI :10.12659/MSM.940387
Med Sci Monit 2023; 29:e940387