Dysregulation of cerebral microvascular endothelial cells plays an important role in the pathogenesis of stroke. However, the underlying mechanisms still need to be elucidated. In the current study, we found that the long non-coding RNA (lncRNA) FAL1 was significantly reduced in response to oxygen-glucose deprivation and reoxygenation (OGD/R) stimulation in human primary brain microvascular endothelial cells (HBMVECs). Interestingly, overexpression of FAL1 ameliorated OGD/R-induced oxidative stress by reducing the production of reactive oxygen species (ROS) and increasing the level of reduced glutathione (GSH). Also, overexpression of FAL1 suppressed OGD/R-induced secretions of interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1), and high mobility group box-1 (HMGB-1). We then found that OGD/R-induced reduction of cell viability and release of lactate dehydrogenase (LDH) were prevented by overexpression of FAL1. Additionally, exposure to OGD/R significantly reduced the phosphorylated levels of PAK1 and AKT as well as the total level of proliferating cell nuclear antigen (PCNA), which was restored by overexpression of FAL1. Importantly, overexpression of FAL1 restored OGD/R-induced reduction in the expression of endothelial nitric oxide synthase (eNOS) and the subsequent release of nitric oxide (NO). Our results implicate that FAL1 might be involved in the process of brain endothelial cell damage.

中文翻译：

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lncRNA FAL1通过调节PAK1来防止缺氧-再氧化引起的脑内皮损伤。

脑微血管内皮细胞的失调在中风的发病机理中起重要作用。但是，仍然需要阐明其基本机制。在当前的研究中，我们发现长非编码RNA（lncRNA）FAL1在人原代脑微血管内皮细胞（HBMVEC）中对氧葡萄糖剥夺和复氧（OGD / R）刺激产生了显着减少。有趣的是，FAL1的过表达通过减少活性氧（ROS）的产生并增加还原型谷胱甘肽（GSH）的水平来改善OGD / R诱导的氧化应激。此外，FAL1的过表达抑制了OGD / R诱导的白介素6（IL-6），单核细胞趋化蛋白1（MCP-1）和高迁移率box-1（HMGB-1）的分泌。然后，我们发现OGD / R诱导的细胞活力降低和乳酸脱氢酶（LDH）释放被FAL1的过表达阻止。此外，暴露于OGD / R会显着降低PAK1和AKT的磷酸化水平以及增殖细胞核抗原（PCNA）的总水平，该水平可通过FAL1的过表达恢复。重要的是，FAL1的过表达恢复了OGD / R诱导的内皮一氧化氮合酶（eNOS）表达的减少以及随后释放的一氧化氮（NO）。我们的结果暗示FAL1可能参与了脑内皮细胞损伤的过程。暴露于OGD / R会显着降低PAK1和AKT的磷酸化水平，以及增殖细胞核抗原（PCNA）的总水平，而FAL1的过表达可恢复该水平。重要的是，FAL1的过表达恢复了OGD / R诱导的内皮一氧化氮合酶（eNOS）表达的减少以及随后释放的一氧化氮（NO）。我们的结果暗示FAL1可能参与了脑内皮细胞损伤的过程。暴露于OGD / R会显着降低PAK1和AKT的磷酸化水平，以及增殖细胞核抗原（PCNA）的总水平，而FAL1的过表达可恢复该水平。重要的是，FAL1的过表达恢复了OGD / R诱导的内皮一氧化氮合酶（eNOS）表达的减少以及随后释放的一氧化氮（NO）。我们的结果暗示FAL1可能参与了脑内皮细胞损伤的过程。