Center for Translational Medicine, the Third People's Hospital of Longgang District, Shenzhen, PR China.
Inner Mongolia Key Laboratory of Hypoxic Translational Medicine, Baotou, PR China.
Mol Biol Rep. 2024 Jul 13;51(1):808. doi: 10.1007/s11033-024-09774-1.
Endothelial cells (ECs) can confer neuroprotection by secreting molecules. This study aimed to investigate whether DNA methylation contributes to the neuroprotective gene expression induced by hypoxia preconditioning (HPC) in ECs and to clarify that the secretion of molecules from HPC ECs may be one of the molecular mechanisms of neuroprotection.
Human microvascular endothelial cell-1 (HMEC-1) was cultured under normal conditions (C), hypoxia(H), and hypoxia preconditioning (HPC), followed by the isolation of culture medium (CM). SY5Y cell incubated with the isolated CM from HMEC-1 was exposed to oxygen-glucose deprivation (OGD). The DNA methyltransferases (DNMTs), global methylation level, miR-126 and its promotor DNA methylation level in HMEC-1 were measured. The cell viability and cell injury in SY5Y were detected.
HPC decreased DNMTs level and global methylation level as well as increased miR-126 expression in HMEC-1. CM from HPC treated HMEC-1 also relieved SY5Y cell damage, while CM from HMEC-1 which over-expression of miR-126 can reduce injury in SY5Y under OGD condition.
These findings indicate EC may secrete molecules, such as miR-126, to execute neuroprotection induced by HPC through regulating the expression of DNMTs.
内皮细胞 (ECs) 通过分泌分子发挥神经保护作用。本研究旨在探讨 DNA 甲基化是否有助于 ECs 缺氧预处理 (HPC) 诱导的神经保护基因表达，并阐明 HPC ECs 分泌的分子可能是神经保护的一种分子机制。
在正常条件 (C)、缺氧 (H) 和缺氧预处理 (HPC) 下培养人微血管内皮细胞-1 (HMEC-1)，然后分离培养上清液 (CM)。将 SY5Y 细胞与从 HMEC-1 中分离的 CM 孵育，然后使其暴露于氧葡萄糖剥夺 (OGD)。测量 HMEC-1 中的 DNA 甲基转移酶 (DNMTs)、整体甲基化水平、miR-126 及其启动子 DNA 甲基化水平。检测 SY5Y 中的细胞活力和细胞损伤。
HPC 降低了 HMEC-1 中的 DNMTs 水平和整体甲基化水平，同时增加了 miR-126 的表达。经 HPC 处理的 HMEC-1 的 CM 也减轻了 SY5Y 细胞的损伤，而过表达 miR-126 的 HMEC-1 的 CM 可减少 OGD 条件下 SY5Y 中的损伤。
这些发现表明，EC 可能通过调节 DNMTs 的表达来分泌分子，如 miR-126，从而发挥由 HPC 诱导的神经保护作用。
