SIRT1 regulates the human alveolar epithelial A549 cell apoptosis induced by Pseudomonas aeruginosa lipopolysaccharide.
BACKGROUND
Sirtuin1 (SIRT1) is an NAD(+)-dependent deacetylase that plays an inhibitory role in cell apoptosis, which is associated with p53 deacetylation. Lipopolysaccharide (LPS) is a key virulence factor produced by Pseudomonas aeruginosa and plays an important role in mediating the interactions between the bacterium and its host. However, the effect of SIRT1 in the regulation of LPS-induced human alveolar epithelial A549 cells apoptosis is unknown.


METHODS
Cell viability, apoptosis and reactive oxygen species (ROS) production were first examined in A549 cells that were treated with LPS. Relative cell signaling pathways were further explored by western blot analysis.


RESULTS
Exposure of A549 cells to LPS decreased cell viability in a concentration- and time- dependent manner. LPS stimulated cell apoptosis and ROS production while inhibiting the expression of SIRT1 in A549 cells. Activation of SIRT1 by exposure to resveratrol significantly reversed the effects of LPS on A549 cells. In contrast, inhibition of SIRT1 by nicotinamide had the opposite effects enhancing cell apoptosis and ROS production.


CONCLUSIONS
SIRT1 plays an important role in regulating the human alveolar epithelial A549 cell apoptosis process induced by LPS.
Graduate School of Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
Xiaoli
X
Liu
Kuiqing
K
Shao
Tieying
T
Sun
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D008070:Lipopolysaccharides / Q000633:toxicity*; D009536:Niacinamide / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011550:Pseudomonas aeruginosa / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077185:Resveratrol; D056564:Sirtuin 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013267:Stilbenes / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D000972:Antineoplastic Agents, Phytogenic; D008070:Lipopolysaccharides; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D013267:Stilbenes; D016159:Tumor Suppressor Protein p53; D009536:Niacinamide; D056564:Sirtuin 1; D000077185:Resveratrol