粒体自噬
神经保护
安普克
线粒体
缺血
自噬
再灌注损伤
药理学
细胞凋亡
激活剂(遗传学)
细胞生物学
医学
磷酸化
化学
生物
内科学
生物化学
蛋白激酶A
受体
作者
Ying Cai,Eryan Yang,Xiuhua Yao,Xuebin Zhang,Qixue Wang,Yunfei Wang,Ji Liu,Weijia Fan,Kaikai Yi,Chunsheng Kang,Jialing Wu
出处
期刊:Redox biology
[Elsevier]
日期:2020-11-07
卷期号:38: 101792-101792
被引量:122
标识
DOI:10.1016/j.redox.2020.101792
摘要
Autophagy of mitochondria, termed mitophagy, plays an important role in cerebral ischemia-reperfusion (IR) injury, but the mechanism is not yet clear. Tissue-type plasminogen activator (tPA) is the most important thrombolytic drug in the clinical treatment of ischemic stroke and has neuroprotective effects. Here, we explored the effects of tPA on neuronal apoptosis and mitophagy following IR. We found that knocking out the tPA gene significantly aggravated brain injury and increased neuronal apoptosis and mitochondrial damage. Exposure of neurons to tPA reduced injury severity and protected mitochondria. Further studies demonstrated that this protective effect of tPA was achieved via regulation of FUNDC1-mediated mitophagy. Furthermore, we found that tPA enhanced the expression level of FUNDC1 by activating the phosphorylation of AMPK. In summary, our results confirm that tPA exerts neuroprotective effects by increasing the phosphorylation of AMPK and the expression of FUNDC1, thereby inhibiting apoptosis and improving mitochondrial function.
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