title: Propofol prevents autophagic cell death following oxygen and glucose deprivation in PC12 cells and cerebral ischemia-reperfusion injury in rats.
abstract: BACKGROUND
  Propofol exerts protective effects on neuronal cells, in part through the inhibition of programmed cell death. Autophagic cell death is a type of programmed cell death that plays elusive roles in controlling neuronal damage and metabolic homeostasis. We therefore studied whether propofol could attenuate the formation of autophagosomes, and if so, whether the inhibition of autophagic cell death mediates the neuroprotective effects observed with propofol.
  
  
  RESULTS
  The cell model was established by depriving the cells of oxygen and glucose (OGD) for 6 hours, and the rat model of ischemia was introduced by a transient two-vessel occlusion for 10 minutes. Transmission electron microscopy (TEM) revealed that the formation of autophagosomes and autolysosomes in both neuronal PC12 cells and pyramidal rat hippocampal neurons after respective OGD and ischemia/reperfusion (I/R) insults. A western blot analysis revealed that the autophagy-related proteins, such as microtubule-associated protein 1 light chain 3 (LC3-II), Beclin-1 and class III PI3K, were also increased accordingly, but cytoprotective Bcl-2 protein was decreased. The negative effects of OGD and I/R, including the formation of autophagosomes and autolysosomes, the increase in LC3-II, Beclin-1 and class III PI3K expression and the decline in Bcl-2 production were all inhibited by propofol and specific inhibitors of autophagy, such as 3-methyladenine (3-MA), LY294002 and Bafilomycin A1 (Baf),. Furthermore, in vitro OGD cultures and in vivo I/R rats showed an increase in cell survival following the administration of propofol, as assessed by an MTT assay or histochemical analyses.
  
  
  CONCLUSIONS
  Our data suggest that propofol can markedly attenuate autophagic processes via the decreased expression of autophagy-related proteins in vitro and in vivo. This inhibition improves cell survival, which provides a novel explanation for the pleiotropic effects of propofol that benefit the nervous system.
authors.affiliation: Department of Anesthesiology, Shanghai Sixth People's Hospital Affiliated with Shanghai Jiaotong University, Shanghai, China.
authors.forename: Derong
authors.initials: D
authors.lastname: Cui
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Aihua
authors.initials: A
authors.lastname: Qi
authors.forename: Quanhong
authors.initials: Q
authors.lastname: Zhou
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects*; D000071186:Beclin-1; D002470:Cell Survival / Q000187:drug effects*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D058546:Class III Phosphatidylinositol 3-Kinases / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D016716:PC12 Cells; D015742:Propofol / Q000008:administration & dosage*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017966:Pyramidal Cells / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury
chemical_list: D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; D058546:Class III Phosphatidylinositol 3-Kinases; D005947:Glucose; D008869:Microtubule-Associated Proteins; D010100:Oxygen; D015742:Propofol; D019253:Proto-Oncogene Proteins c-bcl-2; C512829:Becn1 protein, rat; C526109:Anxa3 protein, rat