Document Detail


Propofol prevents autophagic cell death following oxygen and glucose deprivation in PC12 cells and cerebral ischemia-reperfusion injury in rats.
MedLine Citation:
PMID:  22509406     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
METHODOLOGY/PRINCIPAL FINDINGS: 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/SIGNIFICANCE: 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:
Derong Cui; Li Wang; Aihua Qi; Quanhong Zhou; Xiaoli Zhang; Wei Jiang
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-04-11
Journal Detail:
Title:  PloS one     Volume:  7     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2012  
Date Detail:
Created Date:  2012-04-17     Completed Date:  2012-08-07     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e35324     Citation Subset:  IM    
Affiliation:
Department of Anesthesiology, Shanghai Sixth People's Hospital Affiliated with Shanghai Jiaotong University, Shanghai, China.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis Regulatory Proteins / metabolism
Autophagy / drug effects*
Cell Survival / drug effects*
Cerebral Cortex / drug effects,  metabolism
Class III Phosphatidylinositol 3-Kinases / metabolism
Gene Expression Regulation / drug effects*
Glucose / metabolism
Male
Microtubule-Associated Proteins / metabolism
Oxygen / metabolism
PC12 Cells
Propofol / administration & dosage*
Proto-Oncogene Proteins c-bcl-2 / metabolism
Pyramidal Cells / drug effects*,  metabolism
Rats
Rats, Sprague-Dawley
Reperfusion Injury*
Chemical
Reg. No./Substance:
0/Apoptosis Regulatory Proteins; 0/LC3 protein, rat; 0/Microtubule-Associated Proteins; 0/Proto-Oncogene Proteins c-bcl-2; 0/beclin 1 protein, rat; 2078-54-8/Propofol; 50-99-7/Glucose; 7782-44-7/Oxygen; EC 2.7.1.137/Class III Phosphatidylinositol 3-Kinases
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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