14,15-EET Suppresses Neuronal Apoptosis in Ischemia-Reperfusion Through the Mitochondrial Pathway
| Autor: | Hui-Xia Geng, Jin-Bo Deng, Xiao-Qing Wang, Lai Wang, Li Zhang, Rui-Ping Li, Jiexin Deng, Ying-Ge Li |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male Caspase 3 Apoptosis Mitochondrion Biochemistry Mitochondrial apoptosis-induced channel Neuroprotection 03 medical and health sciences Cellular and Molecular Neuroscience Phosphatidylinositol 3-Kinases 0302 clinical medicine 8 11 14-Eicosatrienoic Acid Downregulation and upregulation Animals PI3K/AKT/mTOR pathway biology Chemistry Cytochrome c Cytochromes c General Medicine Cell biology Mitochondria Mice Inbred C57BL 030104 developmental biology Reperfusion Injury cardiovascular system biology.protein 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | Neurochemical research. 42(10) |
| ISSN: | 1573-6903 |
| Popis: | 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 that 14,15-EET could suppress neuronal apoptosis and reduce infarct volume through the mitochondrial apoptotic pathway. Furthermore, the PI3K/AKT pathway also appears to be involved in the neuroprotection against ischemia-reperfusion by 14,15-EET. |
| Databáze: | OpenAIRE |
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