下调和上调
基因敲除
缺氧(环境)
化学
活性氧
细胞凋亡
神经保护
基因沉默
再灌注损伤
线粒体
细胞生物学
缺血
药理学
医学
生物
生物化学
内科学
氧气
基因
有机化学
作者
Yaqi Shen,Zhuqing Shen,Ling-yan Guo,Qiuyan Zhang,Zhijun Wang,Lei Miao,Minjun Wang,Jiang Wu,Wei Guo,Yizhun Zhu
出处
期刊:Nitric Oxide
[Elsevier]
日期:2018-08-01
卷期号:78: 11-21
被引量:30
标识
DOI:10.1016/j.niox.2018.05.004
摘要
Ischemic stroke is one of the leading causes of death worldwide. MicroRNAs (miRNAs) have been reported to be implicated in cerebral hypoxia injury and could serve as a therapeutic target. As the third gasotransmitter, hydrogen sulfide (H2S) plays a critical role in hypoxia-induced injury in the central nervous system. Cystathionine β-synthase (CBS) is the main enzyme catalyzing the production of H2S in brain. The objective of this study was to investigate the effect of miR-125b-5p on protecting against oxygen and glucose deprivation (OGD) injury in PC-12 cells by regulating CBS and H2S generation. The level of miR-125b-5p was increased in the rat MCAO model as well as OGD model in PC-12 cells. Meanwhile, CBS expression was remarkably downregulated. Overexpression of miR-125b-5p reduced CBS expression, decreased the H2S generation, and deteriorated OGD injury in PC-12 cells. On the contrary, silencing miR-125b-5p protected PC-12 cells from OGD injury by upregulated CBS and H2S levels. We found the protective effect of miR-125b-5p inhibition was associated with anti-oxidative and anti-apoptotic cell signaling through decreasing ROS level and reducing mitochondrial membrane potential (ΔΨm). Furthermore, the protective effect was absent when CBS was knockdown in PC-12 cells. Our research discovered the regulation of CBS by miR-125b-5p. Besides, we provide the evidence for the therapeutic potential of miR-125b-5p inhibition for cerebral ischemia via CBS/H2S pathway.
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