MiR-494-3p Upregulation Exacerbates Cerebral Ischemia Injury by Targeting Bhlhe40
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Purpose: Cerebral ischemia is related to insufficient blood supply and is characterized by abnormal reactive oxygen species(ROS) production and cell apoptosis. Previous studies have revealed a key role for basic helix-loop-helix family member e40 (Bhlhe40)in oxidative stress and cell apoptosis. This study aimed to investigate the roles of miR-494-3p in cerebral ischemia/reperfusion(I/R) injury. Materials and Methods: A mouse middle cerebral artery occlusion (MCAO/R) model was established to mimic cerebral ischemiain vivo. Brain infarct area was assessed using triphenyl tetrazolium chloride staining. Oxygen-glucose deprivation/reoxygenation(OGD/R) operation was adopted to mimic neuronal injury in vitro. Cell apoptosis was analyzed by flow cytometry. Therelationship between miR-494-3p and Bhlhe40 was validated by luciferase reporter and RNA immunoprecipitation assays. Results: Bhlhe40 expression was downregulated both in MCAO/R animal models and OGD/R-induced SH-SY5Y cells. Bhlhe40overexpression inhibited cell apoptosis and reduced ROS production in SH-SY5Y cells after OGD/R treatment. MiR-494-3p wasverified to bind to Bhlhe40 and negatively regulate Bhlhe40 expression. Additionally, cell apoptosis and ROS production in OGD/R-treated SH-SY5Y cells were accelerated by miR-494-3p overexpression. Rescue experiments suggested that Bhlhe40 could reversethe effects of miR-494-3p overexpression on ROS production and cell apoptosis. Conclusion: MiR-494-3p exacerbates brain injury and neuronal injury by regulating Bhlhe40 after I/R.
Abstract
Purpose: Cerebral ischemia is related to insufficient blood supply and is characterized by abnormal reactive oxygen species(ROS) production and cell apoptosis. Previous studies have revealed a key role for basic helix-loop-helix family member e40 (Bhlhe40)in oxidative stress and cell apoptosis. This study aimed to investigate the roles of miR-494-3p in cerebral ischemia/reperfusion(I/R) injury. Materials and Methods: A mouse middle cerebral artery occlusion (MCAO/R) model was established to mimic cerebral ischemiain vivo. Brain infarct area was assessed using triphenyl tetrazolium chloride staining. Oxygen-glucose deprivation/reoxygenation(OGD/R) operation was adopted to mimic neuronal injury in vitro. Cell apoptosis was analyzed by flow cytometry. Therelationship between miR-494-3p and Bhlhe40 was validated by luciferase reporter and RNA immunoprecipitation assays. Results: Bhlhe40 expression was downregulated both in MCAO/R animal models and OGD/R-induced SH-SY5Y cells. Bhlhe40overexpression inhibited cell apoptosis and reduced ROS production in SH-SY5Y cells after OGD/R treatment. MiR-494-3p wasverified to bind to Bhlhe40 and negatively regulate Bhlhe40 expression. Additionally, cell apoptosis and ROS production in OGD/R-treated SH-SY5Y cells were accelerated by miR-494-3p overexpression. Rescue experiments suggested that Bhlhe40 could reversethe effects of miR-494-3p overexpression on ROS production and cell apoptosis. Conclusion: MiR-494-3p exacerbates brain injury and neuronal injury by regulating Bhlhe40 after I/R.
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