脂肪酸结合蛋白
神经保护
半影
线粒体
缺血
脂质过氧化
化学
氧化应激
细胞凋亡
药理学
细胞生物学
生物
医学
生物化学
内科学
基因
作者
Qingyun Guo,Ichiro Kawahata,An Cheng,Haoyang Wang,Wenbin Jia,Hiroshi Yoshino,Kohji Fukunaga
出处
期刊:Redox biology
[Elsevier]
日期:2023-02-01
卷期号:59: 102547-102547
被引量:10
标识
DOI:10.1016/j.redox.2022.102547
摘要
We have previously shown that a fatty acid-binding protein7 (FABP7) inhibitor ameliorates cerebral ischemia-reperfusion injury in mice, suggesting an association between FABPs and ischemic neuronal injury. However, the precise role of FABPs in ischemic neuronal injury remains unclear. In this study, we investigated the role of FABPs in ischemia-reperfusion neuronal injury. FABP3, FABP5, and FABP7 were upregulated in the ischemic penumbra regions in mice. However, only FABP3 and FABP5 were expressed in injured neurons. Furthermore, FABP3 and FABP5 accumulated in the mitochondria of ischemic neurons. Overexpressing either FABP3 or FABP5 aggravated the reduced mitochondrial membrane potential and induced cell death in human neuroblastoma SH-SY5Y cells during oxidative stress. This damage was mediated by the formation of BAX-containing pores in the mitochondrial membrane. Moreover, FABP5 mediates lipid peroxidation and generates toxic by-products (i.e., 4-HNE) in SH-SY5Y cells. HY11-08 (HY08), a novel FABP3 and 5 inhibitor that does not act on FABP7, significantly reduced cerebral infarct volume and blocked FABP3/5-induced mitochondrial damage, including lipid peroxidation and BAX-related apoptotic signaling. Thus, FABP3 and FABP5 are key players in triggering mitochondrial damage in ischemic neurons. In addition, the novel FABP inhibitor, HY08, may be a potential neuroprotective treatment for ischemic stroke.
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