14,15-EET Suppresses Neuronal Apoptosis in Ischemia-Reperfusion Through the Mitochondrial Pathway

Neurochemical Research
Hui-Xia GengJie-Xin Deng

Abstract

Neuronal apoptosis mediated by the mitochondrial apoptosis pathway is an important pathological process in cerebral ischemia-reperfusion injury. 14,15-EET, an intermediate metabolite of arachidonic acid, can promote cell survival during ischemia/reperfusion. However, whether the mitochondrial apoptotic pathway is involved this survival mechanism is not fully understood. In this study, we observed that infarct size in ischemia-reperfusion injury was reduced in sEH gene knockout mice. In addition, Caspase 3 activation, cytochrome C release and AIF nuclear translocation were also inhibited. In this study, 14,15-EET pretreatment reduced neuronal apoptosis in the oxygen-glucose deprivation and re-oxygenation group in vitro. The mitochondrial apoptosis pathway was also inhibited, as evidenced by AIF translocation from the mitochondria to nucleus and the reduction in the expressions of cleaved-caspase 3 and cytochrome C in the cytoplasm. 14,15-EET could reduce neuronal apoptosis through upregulation of the ratio of Bcl-2 (anti-apoptotic protein) to Bax (apoptosis protein) and inhibition of Bax aggregation onto mitochondria. PI3K/AKT pathway is also probably involved in the reduction of neuronal apoptosis by EET. Our study suggests tha...Continue Reading

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Citations

Apr 17, 2019·Experimental and Therapeutic Medicine·Wen-Fang ZhangJing-Jing Cui
Feb 1, 2018·Toxicological Sciences : an Official Journal of the Society of Toxicology·Aneesh KarkhanisEric Chun Yong Chan
Sep 26, 2020·Cell Death & Disease·Rui LiuYuanyan Liu
Jan 16, 2019·Journal of Molecular Neuroscience : MN·Qiong WuQuanzhong Chang
Nov 20, 2020·Nutrients·Morteza SarparastKin Sing Stephen Lee
Apr 4, 2021·International Journal of Molecular Sciences·Christian Griñán-FerréMercè Pallàs
Dec 16, 2020·ACS Biomaterials Science & Engineering·Xinlong ZangXuehong Chen

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Methods Mentioned

BETA
gene knockout
pharmacotherapy
nuclear translocation
transfection
protein assay
electrophoreses

Software Mentioned

ImageJ

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