Curcumin Alleviates Oxygen-Glucose-Deprivation/Reperfusion-Induced Oxidative Damage by Regulating miR-1287-5p/LONP2 Axis in SH-SY5Y Cells.

Teng Zhang,Yanbing Ding,Xiaomin Chen,Yueqing Qu

doi:10.1155/2021/5548706

Abstract

Oxidative stress-induced neuronal damage is a main cause of ischemia/reperfusion injury. Curcumin (Cur), the principal constituent extracted from dried rhizomes of Curcuma longa L. (turmeric), exhibits excellent antioxidant effects. Previous studies have indicated that miR-1287-5p was downregulated in patients with ischemic stroke. Additionally, we predicted that Lon Peptidase 2, Peroxisomal (LONP2), which is involved in oxidative stress regulation, is targeted by miR-1287-5p. The aim of the current study is to investigate the effect of Cur on ischemia/reperfusion damage and its underlying mechanism. To mimic ischemia/reperfusion damage environment, SH-SY5Y cells were subjected to oxygen-glucose-deprivation/reperfusion (OGD/R). OGD/R treatment downregulated miR-1287-5p and upregulated LONP2 in SH-SY5Y cells, but Cur alleviated OGD/R-induced oxidative damage and reversed the effect of OGD/R on the expression of miR-1287-5p and LONP2. Furthermore, we confirmed the interactive relationship between miR-1287-5p and LONP2 (negative regulation). We revealed that miR-1287-5p overexpression alleviated OGD/R-induced oxidative damage alleviation, similar to the effect of Cur. MiR-1287-5p inhibition accentuated OGD/R-induced oxidative damage in SH-SY5Y cells, which was reversed by Cur. The expression of LONP2 in OGD/R-treated SH-SY5Y cells was decreased by miR-1287-5p overexpression and increased by miR-1287-5p inhibition, and Cur counteracted the increase in LONP2 expression induced by miR-1287-5p inhibition. In conclusion, we suggest that Cur alleviates OGD/R-induced oxidative damage in SH-SY5Y cells by regulating the miR-1287-5p/LONP2 axis. The findings provide a theoretical basis for the clinical application of curcumin.

Highlights

Ischemic stroke is a condition with one of the highest morbidity and mortality rates worldwide, accounting for 80% of all stroke cases and leading to a series of complications, including cognitive impairment and epilepsy [1, 2]
Since LONP2 was reported to be associated with oxidative stress [25], we selected LONP2 as the target for investigation
The targeting relationship between LONP2 and miR-1287-5p was confirmed using the dual luciferase reporter assay. miR-1287-5p mimics reduced the luciferase activity of wild type (WT) LONP2 (Figures 1(b) and 1(c)), demonstrating that binding sites exist between miR-1287-5p and LONP2

Summary

Introduction

Ischemic stroke is a condition with one of the highest morbidity and mortality rates worldwide, accounting for 80% of all stroke cases and leading to a series of complications, including cognitive impairment and epilepsy [1, 2]. Recombinant tissue-type plasminogen activator is the only effective drug for ischemic stroke therapy that has been approved by the Food and Drug Administration, but its use is limited by the risk of cerebral hemorrhaging and the narrow therapeutic window [3, 4]. Ischemic stroke is mainly caused by the coexistence of multiple complex factors, such as inflammation, oxidative stress, blood-brain barrier disorder, platelet activation, and neuronal cell apoptosis, leading to brain injury [7,8,9,10]. It is of great significance to deeply explore the molecular mechanism of ischemic stroke and provide new targets for clinical treatment

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