线粒体通透性转换孔
MPTP公司
MAPK/ERK通路
药理学
线粒体
缺血
细胞凋亡
再灌注损伤
化学
激酶
线粒体膜转运蛋白
医学
程序性细胞死亡
细胞生物学
生物
生物化学
内科学
内分泌学
线粒体内膜
多巴胺能
多巴胺
作者
Ping Huang,Sipeng Wu,Ning Wang,Sai Wang Seto,Dennis Chang
出处
期刊:Phytomedicine
[Elsevier]
日期:2021-05-01
卷期号:85: 153532-153532
被引量:17
标识
DOI:10.1016/j.phymed.2021.153532
摘要
Mitochondria are key cellular organelles that are essential for cell fate decisions. Hydroxysafflor yellow A (HSYA) has displayed an impressively essential role in protection of cerebral ischemia/reperfusion (I/R). However, the mitochondrial effect of HSYA on Brain Microvascular Endothelial Cells (BMECs) under I/R remains to be largely unclear. To evaluate the protective effects of HSYA-mediated mitochondrial permeability transition pore (mPTP) on cerebral I/R injury and its mechanism. Cerebral I/R injury was established by the model of Middle cerebral artery occlusion (MCAO) in rats. Furthermore, to further clarify the relevant mechanism of HSYA's effects on mPTP, inhibition of extracellular regulated protein kinases (ERK) with U0126 and transfect with Cyclophilin D (CypD) SiRNA to reversely verified whether the protective effects of HSYA were exerted by regulating the Mitogen-activated protein kinase kinase (MEK)/ERK/CypD pathway. HSYA treatment significantly increased BMECs viability, decreased the generation of ROS, opening of mPTP and translocation of cytochrome c after OGD/R. In addition to inhibited CypD, HSYA potentiated MEK and increased phosphorylation of ERK expression in BMECs, inhibited apoptosis mediated by mitochondrial. Notably, HSYA also significantly ameliorated neurological deficits and decreased the infarct volume in rats. HSYA reduced the CytC export from mitochondrial by inhibited the open of mPTP via MEK/ERK/CypD pathway, contributing to the protection of I/R. Thus, our study not only revealed novel mechanisms of HSYA for its anti-I/R function, but also provided a template for the design of novel mPTP inhibitor for the treatment of various mPTP-related diseases.
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