Article
Mechanisms Mediating Propofol Protection of Pulmonary Epithelial Cells Against Lipopolysaccharide-Induced Cell Death
Clinical and Experimental Pharmacology and Physiology
Document Type
Article
Publication Date
5-1-2012
Disciplines
Abstract
- Propofol (2,6-diisopropylphenol) is an anaesthetic agent with anti-oxidant properties. The aim of the present study was to determine whether propofol can protect pulmonary epithelial (A549) cells against lipopolysaccharide (LPS)-induced cell death and, if so, the mechanisms involved.
- The effects of LPS alone and in combination with propofol on A549 cell death were investigated. Cell viability was determined using the colourimetric 3-(4,5-dimethyl-2 thiazoyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Apoptotic A549 cells were detected by flow cytometry, as propidium iodide-negative and annexin-V-positive cells, and terminal deoxyribonucleotidyl transferase-mediated dUTP–digoxigenin nick end-labelling (TUNEL). Mitochondrial membrane potential (MMP), caspase 9 activity, Ca2+ concentrations and reactive oxygen species (ROS) were analysed by immunofluorescent methods. Aconitase 2 (ACO2), microtubule-associated light chain 3 (LC3) and beclin-1 levels were evaluated using reverse transcription–polymerase chain reaction and/or western blot analysis.
- Exposure of A549 cells to 1–50 μg/mL LPS for 3–24 h resulted in the concentration- and time-dependent induction of cell death. Cell apoptosis accounted for approximately 77% of cell death induced by LPS. Propofol (5–150 μmol/L) concentration-dependently inhibited LPS-induced A549 cell death. This protective effect of propofol was accompanied by prevention of LPS-induced mitochondrial dysfunction (reductions in MMP, ACO2 expression and ATP) and was associated with the inhibition of LPS-induced activation of apoptotic signals (caspase 9 activity, ROS overproduction and Ca2+ accumulation). In addition, propofol blocked LPS-induced overexpression of the autophagy-associated proteins LC3 and beclin-1.
- The data indicate that propofol protects A549 cells against LPS-induced apoptosis, and probably autophagy, by blocking LPS-induced activation of ROS/caspase 9 pathways and upregulation of LC3 and beclin-1, respectively.
DOI
10.1111/j.1440-1681.2012.05694.x
Citation Information
Xiaoxia Gu, Yan Lu, Ji Chen, Huijuan He, et al.. "Mechanisms Mediating Propofol Protection of Pulmonary Epithelial Cells Against Lipopolysaccharide-Induced Cell Death" Clinical and Experimental Pharmacology and Physiology Vol. 39 Iss. 5 (2012) p. 447 - 453 ISSN: 0305-1870 Available at: http://works.bepress.com/ji_bihl/10/