title: Apoptosis induced by pneumolysin in human endothelial cells involves             mitogen-activated protein kinase phosphorylation.
abstract: Pneumolysin (Ply) is an essential virulence factor of S. pneumoniae, which             can induce apoptosis in a variety of host cells to facilitate infection of pathogenic             bacteria by as yet unclear mechanisms. To confirm the apoptosis-inducing properties             of pneumolysin in endothelial cells, human umbilical vein endothelial cells (HUVECs)             were exposed to pneumolysin. The proliferation of HUVECs was inhibited by pneumolysin             in a dose- and time-dependent manner. Flow cytometry analysis and ultrastructural             changes of the cells indicated the apoptotic response. Exposure to pneumolysin             significantly increased the number of apoptotic cells and the activities of caspases-3             and -8. This change was associated with activation of p38 mitogen-activated protein             kinase (MAPK) and suppression of extracellular signaling regulation kinase (ERK)1/2.             Pre-exposure to the p38 MAPK inhibitor SB-203850 prevented human endothelial cells             from apoptosis induced by pneumolysin. In conclusion, these findings demonstrate             that pneumolysin induces apoptosis in endothelial cells and the involvement of             p38 MAPK activation and ERK1/2 deactivation.
authors.affiliation: Key Laboratory of Laboratory Medical Diagnostics, Ministry of Education, Faculty of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, PR China.
authors.forename: Aie
authors.initials: A
authors.lastname: Zhou
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.forename: Kai
authors.initials: K
authors.lastname: Lan
authors.forename: Xuemei
authors.initials: X
authors.lastname: Zhang
authors.forename: Wenchun
authors.initials: W
authors.lastname: Xu
authors.forename: Yibing
authors.initials: Y
authors.lastname: Yin
authors.forename: Dairong
authors.initials: D
authors.lastname: Li
authors.forename: Jun
authors.initials: J
authors.lastname: Yuan
authors.forename: Yujuan
authors.initials: Y
authors.lastname: He
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001426:Bacterial Proteins / Q000494:pharmacology; D020169:Caspases / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology* / Q000648:ultrastructure; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology; D013301:Streptolysins / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D007093:Imidazoles; D011725:Pyridines; D013301:Streptolysins; C032290:plY protein, Streptococcus pneumoniae; D048049:Extracellular Signal-Regulated MAP Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D020169:Caspases; C093642:SB 203580