title: Sevoflurane Post-conditioning Protects Primary Rat Cortical Neurons Against Oxygen-Glucose Deprivation/Resuscitation: Roles of Extracellular Signal-Regulated Kinase 1/2 and Bid, Bim, Puma.
abstract: Temporal post-conditioning to induce neuroprotection against brain ischemia-reperfusion injury insult is considered to be an effective intervention, but the exact mechanisms of sevoflurane post-conditioning are poorly understood. Extracellular signal-related kinases 1/2 (Erk1/2) play a pivotal role in the cell growth and proliferation. The essential axis of activator Bid, Bim, Puma (BH3s) and BAX, BAK in activating the mitochondrial death program might offer common ground for cell death signal. We hypothesized that, sevoflurane post-conditioning might inhibit the expression of Bid, Bim and Puma and is activated by phosphor-Erk1/2 to reduce neuronal death. To test this hypothesis, we exposed primary cultured cortical neurons to oxygen-glucose deprivation for 1 h and resuscitation for 24 h (OGD/R). The assays of MTT, propidium iodide uptake, JC-1 fluorescence and western blot demonstrated that OGD/R exposure reduced cell viability, increased cell death, decreased mitochondrial membrane potential and the expressions of Bid, Bim, and Puma. Inhibition of Erk1/2 phosphorylation could partially attenuate 2 % of sevoflurane post-conditioning mediated increase in neuronal viability and mitochondrial membrane potential, and also a decrease in cell death and expression of Bid, Bim and Puma after OGD/R treatment. The results demonstrated that, the protection of sevoflurane post-conditioning markedly reducing death of cortical neurons exposed to OGD/R could be correlated with down-regulation of Bid, Bim and Puma expression mediated by phosphorylation/activation of Erk1/2.
authors.affiliation: Department of Anesthesiology, First Affiliated Hospital, China Medical University, Shenyang, China.
authors.forename: Limin
authors.initials: L
authors.lastname: Zhang
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Zhao
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Jiang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D051017:Apoptosis Regulatory Proteins / Q000502:physiology*; D051023:BH3 Interacting Domain Death Agonist Protein / Q000502:physiology*; D000072224:Bcl-2-Like Protein 11; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000172:deficiency*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D008565:Membrane Proteins / Q000502:physiology*; D008738:Methyl Ethers / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D010100:Oxygen / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077149:Sevoflurane
chemical_list: D051017:Apoptosis Regulatory Proteins; D051023:BH3 Interacting Domain Death Agonist Protein; 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; D000077149:Sevoflurane; D005947:Glucose; D010100:Oxygen