MicroRNA-365 Knockdown Prevents Ischemic Neuronal Injury by Activating Oxidation Resistance 1-Mediated Antioxidant Signals
- 28 Downloads
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.
KeywordsMicroRNA Ischemic stroke Neuronal damage Oxidative stress Neuroprotection
This work was supported by grants from the National Natural Science Foundation of China (81030020, 81571197, and 81771268) and the National Education Program of China (J0730860).
Conflict of interest
The authors claim that there are no conflicts of interest.
- 3.Li XJ, Zhang LM, Gu J, Zhang AZ, Sun FY. Melatonin decreases production of hydroxyl radical during cerebral ischemia-reperfusion. Acta Pharmacol Sin 1997, 18: 394–396.Google Scholar
- 7.Baker K, Marcus CB, Huffman K, Kruk H, Malfroy B, Doctrow SR. Synthetic combined superoxide dismutase catalase mimetics are protective as a delayed treatment in a rat stroke model: a key role for reactive oxygen species in ischemic brain injury. J Pharmacol Exp Ther 1998, 284: 215–221.Google Scholar
- 34.Kuo LJ, Yang LX. Gamma-H2AX - a novel biomarker for DNA double-strand breaks. In Vivo 2008, 22: 305–309.Google Scholar