Effect of Dl-3-n-butylphthalide on mitochondrial Cox7c in models of cerebral ischemia/reperfusion injury.

Effect of Dl-3-n-butylphthalide on mitochondrial Cox7c in models of cerebral ischemia/reperfusion injury.
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DOI:
10.3389/fphar.2023.1084564
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发表时间:
2023
影响因子:
5.6
通讯作者:
--
中科院分区:
医学2区
文献类型:
--
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一些研究已经证明dl-3-n-丁基苯酞(NBP)对脑缺血的保护作用,这可能与减轻线粒体功能障碍有关。然而,NBP在脑缺血/再灌注中的具体作用机制和靶点尚不清楚。在这项研究中,我们使用化学蛋白质组学方法来寻找NBP的靶标,并确定细胞色素C氧化酶7 c(Cox 7 c)作为NBP的关键相互作用靶标。我们的研究结果表明,NBP抑制线粒体凋亡和活性氧(ROS)的释放,并通过上调Cox 7 c增加ATP的产生。随后,线粒体呼吸能力提高,HIF-1α/VEGF通路上调,有助于维持线粒体膜电位和血脑屏障的完整性,促进血管生成。因此,我们的研究结果为NBP神经保护作用的机制提供了新的见解,并首次提出Cox 7 c通过保护线粒体功能发挥关键作用。
Several studies have demonstrated the protective effect of dl-3-n-Butylphthalide (NBP) against cerebral ischemia, which may be related to the attenuation of mitochondrial dysfunction. However, the specific mechanism and targets of NBP in cerebral ischemia/reperfusion remains unclear. In this study, we used a chemical proteomics approach to search for targets of NBP and identified cytochrome C oxidase 7c (Cox7c) as a key interacting target of NBP. Our findings indicated that NBP inhibits mitochondrial apoptosis and reactive oxygen species (ROS) release and increases ATP production through upregulation of Cox7c. Subsequently, mitochondrial respiratory capacity was improved and the HIF-1α/VEGF pathway was upregulated, which contributed to the maintenance of mitochondrial membrane potential and blood brain barrier integrity and promoting angiogenesis. Therefore, our findings provided a novel insight into the mechanisms underlying the neuroprotective effects of NBP, and also proposed for the first time that Cox7c exerts a critical role by protecting mitochondrial function.
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