Preserving mitochondrial function by inhibiting GRP75 ameliorates neuron injury under ischemic stroke
Preserving mitochondrial function by inhibiting GRP75 ameliorates neuron injury under ischemic stroke
复制标题
通过抑制 GRP75 保护线粒体功能可改善缺血性中风下的神经元损伤
DOI：
10.3892/mmr.2022.12681
复制
发表时间：
2022-03
影响因子：
3.4
通讯作者：
Benhong He
中科院分区：
文献类型：
--
作者：
Bin Wen;Kai Xu;Rui Huang;Teng Jiang;Jian Wang;Jiehui Chen;Juan Chen;Benhong He
缺血性脑卒中是一种危及生命的疾病，与缺血时神经元损伤密切相关。线粒体功能障碍在缺血性脑卒中的病理生理过程中起重要作用。线粒体钙超载导致线粒体功能障碍的发展。然而，线粒体钙超载的潜在机制远未完全揭示。在本研究中，大脑中动脉阻塞（MCAO）和氧和葡萄糖剥夺（OGD）在体外进行。结果表明，MCAO和OGD在体内和体外均引起显著的线粒体功能障碍。线粒体在缺氧条件下变得碎片化，伴随着热休克蛋白75 kDa葡萄糖调节蛋白（GRP75）的上调。抑制GRP75能够有效地改善线粒体钙超载，保护线粒体功能，这可能为缺血性疾病的进一步转化研究提供证据。
Ischemic stroke is a life-threatening disease, which is closely related to neuron damage during ischemia. Mitochondrial dysfunction is essentially involved in the pathophysiological process of ischemic stroke. Mitochondrial calcium overload contributes to the development of mitochondrial dysfunction. However, the underlying mechanisms of mitochondrial calcium overload are far from being fully revealed. In the present study, middle cerebral artery obstruction (MCAO) was performed in vivo and oxygen and glucose deprivation (OGD) in vitro. The results indicated that both MCAO and OGD induced significant mitochondrial dysfunction in vivo and in vitro. The mitochondria became fragmented under hypoxia conditions, accompanied with upregulation of the heat shock protein 75 kDa glucose-regulated protein (GRP75). Inhibition of GRP75 was able to effectively ameliorate mitochondrial calcium overload and preserve mitochondrial function, which may provide evidence for further translational studies of ischemic diseases.