Accumulating evidence suggests that myocyte enhancer factor 2D (MEF2D) is a pro-survival factor for neurons. However, whether MEF2D is involved in protecting neurons from cerebral ischemia/reperfusion injury remains unknown. The current study was designed to investigate the exact role and mechanism of MEF2D in regulating oxygen-glucose deprivation/re-oxygenation (OGD/R)-induced neuronal injury, an in vitro model used to study cerebral ischemia/reperfusion injury. MEF2D expression was significantly induced in neurons in response to OGD/R injury. Functional analysis demonstrated that MEF2D upregulation significantly rescued the decreased viability of OGD/R-injured neurons and suppressed OGD/R-induced apoptosis and reactive oxygen species (ROS) production. By contrast, MEF2D knockdown increased the sensitivity of neurons to OGD/R-induced injury. Moreover, MEF2D overexpression increased the expression of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and enhanced the activation of Nrf2 antioxidant signaling. However, Nrf2 knockdown partially blocked the MEF2D-mediated neuroprotective effect in OGD/R-exposed neurons. Overall, these results reveal that MEF2D overexpression attenuates OGD/R-induced injury by enhancing Nrf2-mediated antioxidant signaling. These findings suggest that MEF2D may serve as a neuroprotective target with a potential application for treatment of cerebral ischemia/reperfusion injury.

中文翻译：

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MEF2D 上调通过增强 Nrf2 激活保护神经元免受氧-葡萄糖剥夺/再氧合诱导的损伤。

越来越多的证据表明，肌细胞增强因子 2D (MEF2D) 是神经元的促存活因子。然而，MEF2D 是否参与保护神经元免受脑缺血/再灌注损伤仍然未知。目前的研究旨在研究 MEF2D 在调节氧-葡萄糖剥夺/再氧合 (OGD/R) 诱导的神经元损伤中的确切作用和机制，这是一种用于研究脑缺血/再灌注损伤的体外模型。MEF2D 表达在响应 OGD/R 损伤的神经元中显着诱导。功能分析表明，MEF2D 上调显着挽救了 OGD/R 损伤神经元的活力降低，并抑制了 OGD/R 诱导的细胞凋亡和活性氧 (ROS) 的产生。相比之下，MEF2D 敲低增加了神经元对 OGD/R 诱导的损伤的敏感性。此外，MEF2D 过表达增加了核因子（红细胞衍生的 2）样 2（Nrf2）的表达，并增强了 Nrf2 抗氧化信号的激活。然而，Nrf2 组合式部分阻断了 OGD/R 暴露神经元中 MEF2D 介导的神经保护作用。总的来说，这些结果表明 MEF2D 过表达通过增强 Nrf2 介导的抗氧化信号来减轻 OGD/R 诱导的损伤。这些发现表明 MEF2D 可作为神经保护靶点，具有治疗脑缺血/再灌注损伤的潜在应用。这些结果表明 MEF2D 过表达通过增强 Nrf2 介导的抗氧化信号来减轻 OGD/R 诱导的损伤。这些发现表明 MEF2D 可作为神经保护靶点，具有治疗脑缺血/再灌注损伤的潜在应用。这些结果表明 MEF2D 过表达通过增强 Nrf2 介导的抗氧化信号来减轻 OGD/R 诱导的损伤。这些发现表明 MEF2D 可作为神经保护靶点，具有治疗脑缺血/再灌注损伤的潜在应用。