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Edaravone, a free radical scavenger, protects neuronal cells’ mitochondria from ischemia by inactivating another new critical factor of the 5-lipoxygenase pathway affecting the arachidonic acid metabolism
- Source :
- Brain Research. 1690:96-104
- Publication Year :
- 2018
- Publisher :
- Elsevier BV, 2018.
-
Abstract
- To investigate the neuroprotective effect of edaravone was dependent on 5-lipoxygenase (5-LOX) signalling pathway or not. Middle cerebral artery occlusion (MCAO) and oxygen glucose deprivation (OGD) were established in SD rats and PC12 cells to mimic ischemic injury. In vivo, edaravone can significantly reduce neurological deficit scores, infarct volume, ROS level and expression of 5-LOX. For in vitro experiment, reduced viability, cell death which occurred via necrosis and apoptosis were shown after OGD and even severer in OGD-reperfusion (OGD-R). Interestingly, edaravone (0.01, 0.1, 1 μmol/L) and caffeic acid (5-LOX inhibitor) can dramatically attenuate OGD/OGD-R injuries. Profoundly, mitochondrial transmembrane potential was ameliorated and cristae membranes (detected by electron microscope) were swollen in OGD/OGD-R cells; however, edaravone preserved the normal ultrastructure of mitochondria and reduced ROS. Astonishingly, immunohistochemistry analyses showed that 5-LOX was first located in the cytosol, dendrites and nuclei of control cells and then translocated to the nuclear membrane after OGD/OGD-R, which indicated the activation of 5-LOX pathway. Edaravone and caffeic acid can inhibit 5-LOX translocation to the nuclear membrane after OGD/OGD-R and reduce cysteinyl leukotrienes (CysLTs), which are metabolites of 5-LOX. Our results are the first to indicate that the protective action of edaravone may function, at least in part, by inhibiting 5-LOX activation, maintaining the ultrastructure and integrated function of mitochondria, thus protecting neuronal cells from ischemia. Furthermore, the instability of mitochondria may be another critical factor in 5-LOX activation.
- Subjects :
- Male
0301 basic medicine
Programmed cell death
Necrosis
Mitochondrion
PC12 Cells
Neuroprotection
Brain Ischemia
03 medical and health sciences
chemistry.chemical_compound
Caffeic Acids
0302 clinical medicine
Edaravone
medicine
Animals
Molecular Biology
Neurons
Arachidonate 5-Lipoxygenase
Arachidonic Acid
Cell Death
Dose-Response Relationship, Drug
General Neuroscience
food and beverages
Free Radical Scavengers
Free radical scavenger
Cell Hypoxia
Mitochondria
Rats
Cell biology
carbohydrates (lipids)
Cytosol
Glucose
Neuroprotective Agents
030104 developmental biology
nervous system
chemistry
Apoptosis
Reperfusion Injury
Neurology (clinical)
medicine.symptom
030217 neurology & neurosurgery
Signal Transduction
Developmental Biology
Subjects
Details
- ISSN :
- 00068993
- Volume :
- 1690
- Database :
- OpenAIRE
- Journal :
- Brain Research
- Accession number :
- edsair.doi.dedup.....9ce03f2ffb70459109cd22719c25b7df