MicroRNA-365 Knockdown Prevents Ischemic Neuronal Injury by Activating Oxidation Resistance 1-Mediated Antioxidant
Jia-Lin Mo1,2, Zhi-Guang Pan3,2, Xiao Chen1,2
1Department of Neurobiology and Institute for Basic Research on Aging and Medicine, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China.
Neuroscience Bulletin
|April 13, 2019
Summary
MicroRNA-365 (miR-365) worsens brain injury and neuronal damage from oxidative stress by reducing Oxidation Resistance 1 (OXR1). Inhibiting miR-365 protects neurons by restoring OXR1 expression and antioxidant signals.
Area of Science:
- Neuroscience
- Molecular Biology
- Biochemistry
Background:
- MicroRNA-365 (miR-365) is implicated in oxidative damage in diabetic rats.
- The role of miR-365 in oxidative stress-mediated neuronal damage post-ischemia remains unclear.
Purpose of the Study:
- To investigate the function of miR-365 in neuronal damage following ischemia and oxidative stress.
- To elucidate the molecular mechanism by which miR-365 affects neuronal survival.
Main Methods:
- Transient middle cerebral artery occlusion model in rats.
- Hydrogen peroxide-induced oxidative stress model in primary cultured neurons.
- Luciferase assays to confirm direct targeting of Oxr1 by miR-365.
- OXR1 knockdown experiments.
Main Results:
- miR-365 exacerbated ischemic brain injury and oxidative stress-induced neuronal damage.
- miR-365 directly targets and inhibits the expression of Oxidation Resistance 1 (OXR1).
- Inhibition of miR-365 (using antagomir) alleviated brain injury and restored OXR1 levels.
- Knockdown of OXR1 abrogated the neuroprotective effects of miR-365 inhibition.
Conclusions:
- miR-365 upregulation promotes oxidative injury by suppressing OXR1 expression.
- Downregulation of miR-365 confers neuroprotection against oxidative stress by enhancing OXR1-mediated antioxidant pathways.
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