Journal
FRONTIERS IN PHYSIOLOGY
Volume 12, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fphys.2021.719753
Keywords
mitoBK(Ca) channel; ethanol preconditioning; oxygen-glucose deprivation and reperfusion (OGD; R); apoptosis; ischemia-reperfusion (I; R) injury; stroke
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Funding
- National Key R&D Program of China [2017YFC1307500]
- Capital Health Research and Development of Special grants [2016-1-2011, 2020-1-2013]
- Beijing-Tianjin-Hebei Cooperative Basic Research Program [H2018206435]
- Heilongjiang Postdoctoral Financial Assistance [LBH-Z17169]
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Low-dose ethanol preconditioning can alleviate neuronal apoptosis during oxygen-glucose deprivation and reperfusion by activating the BKCa channel, and also modulate mitochondrial function by reducing the expression of apoptosis-related proteins.
Ischemia-reperfusion (I/R) injury contributes to the morbidity and mortality of ischemic strokes. As an in vitro model, oxygen-glucose deprivation and reperfusion (OGD/R) exposure induces neuronal injury. Low-dose ethanol preconditioning (EtOH-PC) was reported to alleviate neuronal apoptosis during OGD/R. However, whether the mitochondrial BKCa (mitoBK(Ca)) channel is involved in the neuroprotective effect of EtOH-PC during OGD/R is not clearly defined. This study attempts to explore the mediation of the mitoBK(Ca) channel in the neuroprotective effect of EtOH-PC on OGD/R-induced neuronal apoptosis and the underlying mechanisms. OGD/R model was established using primary cortical neurons that were preincubated with ethanol. Subsequently, the cell viability was measured by CCK-8 assay, and the apoptotic cells were determined by TUNEL assay. Annexin V/7-AAD staining and mitochondrial membrane potential using JC-10 were detected by flow cytometry. Western blot analysis was performed to check the apoptosis-related proteins. In the mixed primary culture, 95% neurofilament-positive cells were cortical neurons. Low-dose EtOH-PC (10 mmol/L) for 24 h significantly attenuated the OGD2h/R24h-induced neuronal apoptosis through activating the BKCa channel. Further investigations suggested that ethanol pretreatment increased the mitochondrial membrane potential (MMP) and downregulated the production of cleaved caspase 3 in OGD/R-injured neurons by activating the mitoBK(Ca) channel. Low-dose ethanol pretreatment significantly attenuated the OGD/R-induced neuronal apoptosis mediated by the mitoBK(Ca) channel which modulated the mitochondrial function by impeding the uncontrolled opening of mitochondrial permeability transition pore (MPTP).
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