title: Sevoflurane post-conditioning protects primary rat cortical neurons against oxygen-glucose deprivation/resuscitation via down-regulation in mitochondrial apoptosis axis of Bid, Bim, Puma-Bax and Bak mediated by Erk1/2.
abstract: Temporal post-conditioning helps provide neuroprotection against brain injury secondary to ischemia-reperfusion and is considered an effective intervention, but the exact mechanism of sevoflurane post-conditioning is unclear. The essential axis involves activator Bid, Bim, Puma (BH3s), Bax, and Bak; activates the mitochondrial death program; and might be involved in a cell death signal. Extracellular signal-related kinases 1/2 (Erk1/2) play a pivotal role in cell growth and proliferation. We hypothesized that sevoflurane post-conditioning might inhibit Bid, Bim, Puma, Bax, and Bak expression and is activated by phosphor-Erk1/2 to decrease neuronal death. To test this hypothesis, we exposed primary cortical neuron cultures to oxygen-glucose deprivation for 1h, along with resuscitation for 24h (OGD/R). MTT assays, propidium iodide uptake (PI), JC-1 fluorescence, and Western blot indicated the following: decreased cell viability (P<0.05); increased cell death (P<0.05); decreased mitochondrial membrane potential (P<0.05); and decreased Bid, Bim, Puma, Bax, and Bak expression with OGD/R exposure. Inhibition of Erk1/2 phosphorylation could attenuate sevoflurane post-conditioning that mediated an increase in neuronal viability and mitochondrial membrane potential, as well as a decrease in cell death and Bid, Bim, Puma, Bax, and Bak expression after OGD/R treatment. The results demonstrated that sevoflurane post-conditioning caused a marked decrease in cortical neuronal death secondary to OGD/R exposure through the downregulation of the mitochondrial apoptosis axis involving Bid, Bim, Puma, Bax, and Bak that was mediated by the phosphorylation/activation of Erk1/2.
authors.affiliation: Department of Anesthesiology, Cangzhou Central Hospital, Cangzhou, China. Electronic address: azai2015@126.com.
authors.forename: Li-Min
authors.initials: LM
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, Shengjing Hospital, China Medical University, Shenyang, China.
authors.forename: Xiao-Chun
authors.initials: XC
authors.lastname: Zhao
authors.affiliation: Department of Anesthesiology, Cangzhou Central Hospital, Cangzhou, China.
authors.forename: Wen-Bo
authors.initials: WB
authors.lastname: Sun
authors.affiliation: Department of Anesthesiology, Cangzhou Central Hospital, Cangzhou, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, First Affiliated Hospital, China Medical University, Shenyang, China.
authors.forename: Xiao-Jing
authors.initials: XJ
authors.lastname: Jiang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis*; D051023:BH3 Interacting Domain Death Agonist Protein / Q000096:biosynthesis; D000072224:Bcl-2-Like Protein 11; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002540:Cerebral Cortex / Q000166:cytology* / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects*; D005947:Glucose / Q000172:deficiency; D000860:Hypoxia / Q000378:metabolism; D057775:Ischemic Postconditioning; D020935:MAP Kinase Signaling System / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000502:physiology; D008565:Membrane Proteins / Q000096:biosynthesis; D008738:Methyl Ethers / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D061251:Primary Cell Culture; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D051381:Rats; D012151:Resuscitation; D000077149:Sevoflurane; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000096:biosynthesis; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis
chemical_list: D051017:Apoptosis Regulatory Proteins; D051023:BH3 Interacting Domain Death Agonist Protein; C494774:Bak1 protein, rat; C533952:Bbc3 protein, rat; D000072224:Bcl-2-Like Protein 11; C000606778:Bcl2l11 protein, rat; C494816:Bid protein, rat; D008565:Membrane Proteins; D008738:Methyl Ethers; D018696:Neuroprotective Agents; D011518:Proto-Oncogene Proteins; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D000077149:Sevoflurane; D005947:Glucose
keywords: Bak; Bax; Bid; Bim; Extracellular signal-related kinases 1/2; Neuroprotection; Puma; Sevoflurane