Senescence marker protein 30 (SMP30) is a senescence marker molecule and identified as a calcium regulatory protein. Currently, SMP30 has emerged as a cytoprotective protein in a wide range of cell types. However, the role of SMP30 in regulating neuronal survival during cerebral ischemia/reperfusion injury remains unclear. In the present study, we aimed to investigate the biological function and regulatory mechanism of SMP30 on neuronal survival using a cellular model induced by oxygen-glucose deprivation/reoxygenation (OGD/R). The results showed that SMP30 expression was significantly decreased by OGD/R exposure in neurons. Functional experiments demonstrated that SMP30 overexpression significantly rescued the decreased cell viability and attenuated the apoptosis and reactive oxygen species generation in OGD/R-exposed neurons. By contrast, SMP30 knockdown exhibited the opposite effect. Mechanism research revealed that SMP30 overexpression contributed to the activation of nuclear factor erythroid 2-related factor (Nrf2)/antioxidant response element (ARE) signaling associated with downregulation of Kelch-like ECH-associated protein (Keap1). Keap1 overexpression or Nrf2 silencing significantly reversed SMP30-mediated neuroprotection against OGD/R-induced injury. Overall, these findings demonstrate that SMP30 overexpression protects neurons from OGD/R-induced apoptosis and oxidative stress by enhancing Nrf2/ARE antioxidant signaling via inhibition of Keap1. These data highlight the importance of the SMP30/Keap1/Nrf2/ARE signaling axis in regulating neuronal survival during cerebral ischemia/reperfusion injury.

衰老标记蛋白 30 (SMP30) 是一种衰老标记分子，被鉴定为钙调节蛋白。目前，SMP30 已成为多种细胞类型中的细胞保护蛋白。然而，SMP30 在调节脑缺血/再灌注损伤期间神经元存活中的作用仍不清楚。在本研究中，我们旨在使用由氧-葡萄糖剥夺/再氧合 (OGD/R) 诱导的细胞模型研究 SMP30 对神经元存活的生物学功能和调节机制。结果表明，暴露于神经元中的 OGD/R 显着降低了 SMP30 的表达。功能实验表明，SMP30 过表达显着挽救了 OGD/R 暴露神经元中降低的细胞活力并减弱了细胞凋亡和活性氧的产生。相比之下，SMP30 敲低表现出相反的效果。机制研究表明，SMP30 过表达有助于激活与 Kelch 样 ECH 相关蛋白 (Keap1) 下调相关的核因子红细胞 2 相关因子 (Nrf2)/抗氧化反应元件 (ARE) 信号。Keap1 过表达或 Nrf2 沉默显着逆转了 SMP30 介导的对 OGD/R 诱导的损伤的神经保护作用。总的来说，这些发现表明 SMP30 过表达通过抑制 Keap1 增强 Nrf2/ARE 抗氧化信号，从而保护神经元免受 OGD/R 诱导的细胞凋亡和氧化应激。这些数据强调了 SMP30/Keap1/Nrf2/ARE 信号轴在调节脑缺血/再灌注损伤期间神经元存活中的重要性。机制研究表明，SMP30 过表达有助于激活与 Kelch 样 ECH 相关蛋白 (Keap1) 下调相关的核因子红细胞 2 相关因子 (Nrf2)/抗氧化反应元件 (ARE) 信号。Keap1 过表达或 Nrf2 沉默显着逆转了 SMP30 介导的对 OGD/R 诱导的损伤的神经保护作用。总的来说，这些发现表明 SMP30 过表达通过抑制 Keap1 增强 Nrf2/ARE 抗氧化信号，从而保护神经元免受 OGD/R 诱导的细胞凋亡和氧化应激。这些数据强调了 SMP30/Keap1/Nrf2/ARE 信号轴在调节脑缺血/再灌注损伤期间神经元存活中的重要性。机制研究表明，SMP30 过表达有助于激活与 Kelch 样 ECH 相关蛋白 (Keap1) 下调相关的核因子红细胞 2 相关因子 (Nrf2)/抗氧化反应元件 (ARE) 信号。Keap1 过表达或 Nrf2 沉默显着逆转了 SMP30 介导的对 OGD/R 诱导的损伤的神经保护作用。总的来说，这些发现表明 SMP30 过表达通过抑制 Keap1 增强 Nrf2/ARE 抗氧化信号，从而保护神经元免受 OGD/R 诱导的细胞凋亡和氧化应激。这些数据强调了 SMP30/Keap1/Nrf2/ARE 信号轴在调节脑缺血/再灌注损伤期间神经元存活方面的重要性。