title: The Effect of Propofol on Mitochondrial Fission during Oxygen-Glucose Deprivation and Reperfusion Injury in Rat Hippocampal Neurons.
abstract: The neuroprotective role of propofol in transient global and focal cerebral ischemia reperfusion (I/R) animal model has recently been highlighted. However, no studies have conducted to explore the relationship between mitochondrial fission/fusion and I/R injury under the intervention of propofol. Moreover, neuroprotective mechanism of propofol is yet unclear. Culturing primary hippocampal cells were subjected to oxygen-glucose deprivation and re-oxygenation (OGD/R) model, as a model of cerebral I/R in vitro. Methods CCK-8 assay was used to test the effect of propofol on cell viability. We examined the effect of propofol on mitochondrial ultrastructure and mitochondrial fission evoked by OGD/R with transmission electron microscopy and immunofluorescence assay. To investigate possible neuroprotective mechanisms, the authors then examined whether propofol could inhibit calcium-overload, calcineurin (CaN) activation and the phosphorylation of dynamin-related protein 1 (Drp1) during the period of OGD/R, as well as the combination of Drp1-ser 637 and fission 1 (Fis1) protein by immunofluorescence assay, ELISA and double-labeling immunofluorescence analysis. Finally, the expression of Drp1-ser 637 and Fis1, apoptosis inducing factor (AIF) and cytochrome C (Cyt C) were detected by western blot. When added in culture media during OGD period, propofol (0.1μM-50μM) could alleviate neurons injury and protect mitochondrial ultrastructure, meanwhile inhibit mitochondrial fission. Furthermore, the concentration of intracellular free Ca2+, CaN activition and the phosphorylation of Drp1-ser637 were suppressed, as well as the translocation and combination of Drp1-ser 637 and Fis1. The authors also found that the expression of Cyt C, AIF, Drp1-ser637 and Fis1 were down-regulated. Notably, high dose of propofol (100μM-200μM) were confirmed to decrease the survival of neurons based on results of cell viability. Propofol could inhibit mitochondrial fission and mitochondrial apoptotic pathway evoked by OGD/R in rat hippocampal neurons, which may be via depressing calcium-overload.
authors: Department of Anesthesiology, the Affiliated Hospital of Qingdao University, Huangdao, Qingdao, Shandong Province, China.
authors: Haibin
authors: H
authors: Wang
authors: Institute of Cerebrovascular Diseases, Affiliated Hospital of Qingdao University, Huangdao, Qingdao, Shandong Province, China.
authors: Shengfa
authors: S
authors: Zheng
authors: Department of Anesthesiology, the Affiliated Hospital of Qingdao University, Huangdao, Qingdao, Shandong Province, China.
authors: Maodong
authors: M
authors: Liu
authors: Department of Anesthesiology, the Affiliated Hospital of Qingdao University, Huangdao, Qingdao, Shandong Province, China.
authors: Changxin
authors: C
authors: Jia
authors: Department of Anesthesiology, the Affiliated Hospital of Qingdao University, Huangdao, Qingdao, Shandong Province, China.
authors: Shilei
authors: S
authors: Wang
authors: Department of Anesthesiology, the Affiliated Hospital of Qingdao University, Huangdao, Qingdao, Shandong Province, China.
authors: Xue
authors: X
authors: Wang
authors: Department of Anesthesiology, the Affiliated Hospital of Qingdao University, Huangdao, Qingdao, Shandong Province, China.
authors: Sha
authors: S
authors: Xue
authors: Department of Anesthesiology, People's Hospital of Rizhao, Rizhao, Shandong Province, China.
authors: Yunliang
authors: Y
authors: Guo
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005947:Glucose / Q000172:deficiency; D006624:Hippocampus / Q000187:drug effects* / Q000503:physiopathology / Q000648:ultrastructure; D000860:Hypoxia / Q000188:drug therapy; D008928:Mitochondria / Q000187:drug effects / Q000648:ultrastructure; D063154:Mitochondrial Dynamics / Q000187:drug effects*; D015742:Propofol / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*
chemical_list: D005947:Glucose; D002118:Calcium; D015742:Propofol