title: Low-Dose Ethanol Preconditioning Protects Against Oxygen-Glucose Deprivation/Reoxygenation-Induced Neuronal Injury By Activating Large Conductance, Ca2+-Activated K+Channels In Vitro.
abstract: Increasing evidence suggests that low to moderate ethanol ingestion protects against the deleterious effects of subsequent ischemia/reperfusion; however, the underlying mechanism has not been elucidated. In the present study, we showed that expression of the neuronal large-conductance, Ca2+-activated K+channel (BKCa) α-subunit was upregulated in cultured neurons exposed to oxygen-glucose deprivation/reoxygenation (OGD/R) compared with controls. Preconditioning with low-dose ethanol (10 mmol/L) increased cell survival rate in neurons subjected to OGD/R, attenuated the OGD/R-induced elevation of cytosolic Ca2+levels, and reduced the number of apoptotic neurons. Western blots revealed that ethanol preconditioning upregulated expression of the anti-apoptotic protein Bcl-2 and downregulated the pro-apoptotic protein Bax. The protective effect of ethanol preconditioning was antagonized by a BKCachannel inhibitor, paxilline. Inside-out patches in primary neurons also demonstrated the direct activation of the BKCachannel by 10 mmol/L ethanol. The above results indicated that low-dose ethanol preconditioning exerts its neuroprotective effects by attenuating the elevation of cytosolic Ca2+and preventing neuronal apoptosis, and this is mediated by BKCachannel activation.
authors.affiliation: Department of Neurology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, China.|Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100050, China.|Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, 100050, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Su
authors.affiliation: Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, 100050, China.|Beijing Institute for Brain Disorders, Beijing, 100069, China.|China National Clinical Research Center for Neurological Diseases, Beijing, 100050, China.
authors.forename: An-Chen
authors.initials: AC
authors.lastname: Guo
authors.affiliation: Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, 100050, China.|Beijing Institute for Brain Disorders, Beijing, 100069, China.
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Li
authors.affiliation: Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100050, China.|Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, 100050, China.|China National Clinical Research Center for Neurological Diseases, Beijing, 100050, China.
authors.forename: Yi-Long
authors.initials: YL
authors.lastname: Zhao
authors.affiliation: Department of Neurology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, China.
authors.forename: Zheng-Yi
authors.initials: ZY
authors.lastname: Qu
authors.affiliation: Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100050, China.|Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, 100050, China.|Beijing Institute for Brain Disorders, Beijing, 100069, China.|China National Clinical Research Center for Neurological Diseases, Beijing, 100050, China.
authors.forename: Yong-Jun
authors.initials: YJ
authors.lastname: Wang
authors.affiliation: Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100050, China.|Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, 100050, China.|Beijing Institute for Brain Disorders, Beijing, 100069, China.|China National Clinical Research Center for Neurological Diseases, Beijing, 100050, China.
authors.forename: Qun
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Neurology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, China. ylz1111@outlook.com.
authors.forename: Yu-Lan
authors.initials: YL
authors.lastname: Zhu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002540:Cerebral Cortex / Q000166:cytology; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D000431:Ethanol / Q000494:pharmacology*; D005947:Glucose / Q000172:deficiency; D000860:Hypoxia / Q000517:prevention & control; D007211:Indoles / Q000494:pharmacology; D051038:Large-Conductance Calcium-Activated Potassium Channel beta Subunits / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010100:Oxygen / Q000494:pharmacology*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013777:Tetrazoles / Q000494:pharmacology; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects* / Q000502:physiology
chemical_list: C524410:1-(3,5-bis(trifluoromethyl)phenyl)-3-(4-bromo-2-(1H-tetrazol-5-yl)phenyl)thiourea; D007211:Indoles; C545899:KCNMB1 protein, rat; D051038:Large-Conductance Calcium-Activated Potassium Channel beta Subunits; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D026902:Potassium Channel Blockers; D013777:Tetrazoles; D000431:Ethanol; C048220:paxilline; D013890:Thiourea; D005947:Glucose; D010100:Oxygen
keywords: Apoptosis; BKCa channel; Ethanol preconditioning; Neuroprotection; Oxygen-glucose deprivation/reoxygenation