14,15-Epoxyeicosatrienoic Acid Protect Against Glucose Deprivation and Reperfusion-Induced Cerebral Microvascular Endothelial Cells Injury by Modulating Mitochondrial Autophagy via SIRT1/FOXO3a Signaling Pathway and TSPO Protein.
14,15-Epoxyeicosatrienoic Acid Protect Against Glucose Deprivation and Reperfusion-Induced Cerebral Microvascular Endothelial Cells Injury by Modulating Mitochondrial Autophagy via SIRT1/FOXO3a Signaling Pathway and TSPO Protein.
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DOI：
10.3389/fncel.2022.888836
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发表时间：
2022
影响因子：
5.3
通讯作者：
中科院分区：
文献类型：
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神经血管系统在控制血液流入脑实质组织中起着至关重要的作用。此外，它还促进神经元生物活性的代谢。脑微血管内皮细胞（MEC）参与介导脑血管相关疾病的进展，包括中风。花生四烯酸在细胞色素P450环氧合酶的催化下可转化为环氧二十碳三烯酸。我们已经报道了Escherichia coli可以保护神经元功能。本研究进一步阐明了14，15-EET在脑微血管内皮细胞保护中的作用及其在氧糖剥夺再灌注（OGD/R）中的可能机制。本研究采用RNA干扰技术干预SIRT 1/FOXO 3a通路，建立TSPO敲低模型，探讨14，15-EET对OGD/R损伤的细胞保护作用。OGD/R处理后，脑MECs活力明显降低，而14，15-EET可逆转此效应。为了进一步证实14，15-EET是否通过SIRT 1/FOXO 3a信号通路和转运蛋白（TSPO）蛋白介导，我们还检测了自噬相关蛋白、线粒体膜电位、凋亡指标、氧自由基等，发现14，15-EET可以调节OGD/R诱导的线粒体自噬。SIRT 1/FOXO 3a信号通路和TSPO调节与14，15-EET对脑MEC的保护作用有关。此外，我们还探讨了SIRT 1/FOXO 3a信号通路与TSPO蛋白之间的潜在关系。本研究揭示了14，15-EET对OGD/R条件下脑MEC的保护作用及其可能机制。
Neurovascular system plays a vital role in controlling the blood flow into brain parenchymal tissues. Additionally, it also facilitates the metabolism in neuronal biological activities. Cerebral microvascular endothelial cells (MECs) are involved in mediating progression of the diseases related to cerebral vessels, including stroke. Arachidonic acid can be transformed into epoxyeicosatrienoic acids (EETs) under the catalysis by cytochrome P450 epoxygenase. We have reported that EETs could protect neuronal function. In our research, the further role of 14,15-EET in the protective effects of cerebral MECs and the potential mechanisms involved in oxygen glucose deprivation and reperfusion (OGD/R) were elucidated. In our study, we intervened the SIRT1/FOXO3a pathway and established a TSPO knock down model by using RNA interference technique to explore the cytoprotective role of 14,15-EET in OGD/R injury. Cerebral MECs viability was remarkably reduced after OGD/R treatment, however, 14,15-EET could reverse this effect. To further confirm whether 14,15-EET was mediated by SIRT1/FOXO3a signaling pathway and translocator protein (TSPO) protein, we also detected autophagy-related proteins, mitochondrial membrane potential, apoptosis indicators, oxygen free radicals, etc. It was found that 14,15-EET could regulate the mitophagy induced by OGD/R. SIRT1/FOXO3a signaling pathway and TSPO regulation were related to the protective role of 14,15-EET in cerebral MECs. Moreover, we also explored the potential relationship between SIRT1/FOXO3a signaling pathway and TSPO protein. Our study revealed the protective role and the potential mechanisms of 14,15-EET in cerebral MECs under OGD/R condition.
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