Open AccessMicroRNA-365 Knockdown Prevents Ischemic Neuronal Injury by Activating Oxidation Resistance 1-Mediated Antioxidant Signals
Author(s) -
Jialin Mo,
Zhiguang Pan,
Xiao Chen,
Lei Yu,
Liyuan Lv,
Cheng Qian,
Feng-Yan Sun
Publication year - 2019
Publication title -
neuroscience bulletin/neuroscience bulletin
Language(s) - English
Resource type - Journals
eISSN - 1673-7067
pISSN - 1995-8218
DOI - 10.1007/s12264-019-00371-y
Subject(s) - downregulation and upregulation , neuroprotection , gene knockdown , oxidative stress , pharmacology , antagomir , medicine , ischemia , microrna , chemistry , apoptosis , biochemistry , gene
MicroRNA-365 (miR-365) is upregulated in the ischemic brain and is involved in oxidative damage in the diabetic rat. However, it is unclear whether miR-365 regulates oxidative stress (OS)-mediated neuronal damage after ischemia. Here, we used a transient middle cerebral artery occlusion model in rats and the hydrogen peroxide-induced OS model in primary cultured neurons to assess the roles of miR-365 in neuronal damage. We found that miR-365 exacerbated ischemic brain injury and OS-induced neuronal damage and was associated with a reduced expression of OXR1 (Oxidation Resistance 1). In contrast, miR-365 antagomir alleviated both the brain injury and OXR1 reduction. Luciferase assays indicated that miR-365 inhibited OXR1 expression by directly targeting the 3'-untranslated region of Oxr1. Furthermore, knockdown of OXR1 abolished the neuroprotective and antioxidant effects of the miR-365 antagomir. Our results suggest that miR-365 upregulation increases oxidative injury by inhibiting OXR1 expression, while its downregulation protects neurons from oxidative death by enhancing OXR1-mediated antioxidant signals.