Sestrin1 (Sesn1) acts as a stress-inducible protein that performs a remarkable cytoprotective function upon diverse cellular stresses. However, whether Sesn1 exerts a cytoprotective role in neurons following cerebral ischemia/reperfusion injury is unknown. The goal of this work was to evaluate the role of Sesn1 in oxygen-glucose deprivation/reoxygenation (OGD/R)-induced neuronal injury in vitro. The induction of Sesn1 was found in neurons exposed to OGD/R treatment. The silencing of Sesn1 rendered neurons more vulnerable to OGD/R injury, while the up-regulation of Sesn1 ameliorated OGD/R-induced neuronal injury by reducing apoptosis and the generation of reactive oxygen species (ROS). Furthermore, the up-regulation of Sesn1 promoted the activity of the nuclear factor-erythroid 2-related factor 2 (Nrf2) by down-regulating the expression of the Kelchlike ECH-associated protein 1 (Keap1). The restoration of Keap1 or the suppression of Nrf2 remarkably abolished the Sesn1-induced neuroprotection effects in OGD/R-exposed neurons. In summary, our work indicates that Sesn1 is a remarkable neuroprotective protein that potentiates Nrf2 activation via Keap1 to ameliorate OGD/R-induced injury.

Sestrin1 (Sesn1) 作为一种应激诱导蛋白，可在多种细胞应激时发挥显着的细胞保护功能。然而，Sesn1 是否在脑缺血/再灌注损伤后的神经元中发挥细胞保护作用尚不清楚。这项工作的目的是评估 Sesn1 在体外氧葡萄糖剥夺/复氧 (OGD/R) 诱导的神经元损伤中的作用. 在暴露于 OGD/R 处理的神经元中发现了 Sesn1 的诱导。Sesn1 的沉默使神经元更容易受到 OGD/R 损伤，而 Sesn1 的上调通过减少细胞凋亡和活性氧 (ROS) 的产生来改善 OGD/R 诱导的神经元损伤。此外，Sesn1 的上调通过下调 Kelchlike ECH 相关蛋白 1 (Keap1) 的表达来促进核因子-红细胞 2 相关因子 2 (Nrf2) 的活性。Keap1 的恢复或 Nrf2 的抑制显着消除了 Sesn1 诱导的 OGD/R 暴露神经元中的神经保护作用。总之，我们的工作表明 Sesn1 是一种显着的神经保护蛋白，可通过 Keap1 增强 Nrf2 激活以改善 OGD/R 诱导的损伤。