Upregulation of Glutaredoxin 2 alleviates oxygen-glucose deprivation/reoxygenation-induced apoptosis and ROS production in neurons by enhancing Nrf2 signaling via modulation of GSK-3β.
Glutaredoxin 2 (GRX2) is an antioxidative protein that exerts a key role in various pathological processes. However, whether GRX2 participates in modulating the oxidative stress during cerebral ischemia/reperfusion, injury is undermined. This study aimed to determine the potential role of GRX2 in regulating oxidative stress in cultured neurons induced by oxygen-glucose deprivation/reoxygenation (OGD/R), a cellular model for study of cerebral ischemia/reperfusion injury in vitro. Here, we showed that GRX2 expression was decreased in neurons subjected to OGD/R exposure. The upregulation of GRX2 markedly improved the viability of OGD/R-exposed neurons and caused a marked reduction in OGD/R-induced apoptosis and reactive oxygen species (ROS) production. On the contrary, depletion of GRX2 exacerbated the OGD/R-induced apoptosis and ROS production in cultured neurons. Moreover, GRX2 upregulation increased nuclear expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and enhanced the activation of Nrf2/ARE signaling associated with modulation of glycogen synthase kinase-3β (GSK-3β) inhibition. Notably, inhibition of Nrf2 markedly abrogated GRX2-mediated protection against OGD/R-induced apoptosis and oxidative stress. Overall, these findings elucidate that GRX2 plays an essential role in regulating the protection against OGD/R-induced apoptosis and oxidative stress in neurons associated with its ability to enhance the activation of Nrf2 via modulation of GSK-3β. Our study indicates that GRX2 may play a key role in modulating neuronal apoptosis and oxidative stress induced by cerebral ischemia/reperfusion injury.
['Wen|Jian|J|', 'Li|Xin|X|', 'Zheng|Shaohua|S|', 'Xiao|Ying|Y|']
D000818:Animals D017209:Apoptosis D002545:Brain Ischemia D002460:Cell Line D054477:Glutaredoxins D000071679:Glycogen Synthase Kinase 3 beta D051379:Mice D051267:NF-E2-Related Factor 2 D009474:Neurons D018384:Oxidative Stress D017382:Reactive Oxygen Species D015427:Reperfusion Injury D015398:Signal Transduction D015854:Up-Regulation
Glutaredoxin 2 Nrf2 GSK-3β OGD/R