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Ischemic brain injury decreases dynamin-like protein 1 expression in a middle cerebral artery occlusion animal model and glutamate-exposed HT22 cells

机译:缺血性脑损伤可降低大脑中动脉闭塞动物模型和谷氨酸暴露的HT22细胞中动力蛋白样蛋白1的表达

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摘要

Dynamin-like protein I (DLP-1) is an important mitochondrial fission and fusion protein that is associated with apoptotic cell death in neurodegenerative diseases. In this study, we investigated DLP-1 expression in a focal cerebral ischemia animal model and glutamate-exposed hippocampal-derived cell line. Middle cerebral artery occlusion (MCAO) was surgically induced in adult male rats to induce focal cerebral ischemic injury. Brain tissues were collected 24 hours after the onset of MCAO. MCAO induces an increase in infarct volume and histopathological changes in the cerebral cortex. We identified a decrease in DLP-1 in the cerebral cortices of MCAO-injured animals using a proteomic approach and Western blot analysis. Moreover, glutamate treatment significantly decreased DLP-1 expression in a hippocampal-derived cell line. The decrease in DLP-1 indicates mitochondrial dysfunction. Thus, these results suggest that neuronal cell injury induces a decrease in DLP-1 levels and consequently leads to neuronal cell death.
机译:动力蛋白样蛋白I(DLP-1)是一种重要的线粒体分裂和融合蛋白,与神经变性疾病中的凋亡细胞死亡有关。在这项研究中,我们调查了DLP-1在局灶性脑缺血动物模型和谷氨酸暴露的海马来源的细胞系中的表达。成年雄性大鼠通过手术诱发大脑中动脉闭塞(MCAO),以引起局灶性脑缺血损伤。 MCAO发作24小时后收集脑组织。 MCAO引起脑皮质梗死体积的增加和组织病理学改变。我们使用蛋白质组学方法和蛋白质印迹分析确定MCAO受伤的动物的大脑皮质中DLP-1的减少。此外,谷氨酸处理显着降低了海马来源的细胞系中DLP-1的表达。 DLP-1的减少表明线粒体功能障碍。因此,这些结果表明神经元细胞损伤导致DLP-1水平降低,并因此导致神经元细胞死亡。

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