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: Aie Zhou, Hong Wang, Kai Lan, Xuemei Zhang, Wenchun Xu, Yibing Yin, Dairong Li, Jun Yuan, Yujuan He
• Journal: International journal of molecular medicine (Int J Mol Med) Vol. 29 Issue 6 Pg. 1025-30 (Jun 2012) ISSN: 1791-244X [Electronic] Greece
• PMID: 22446935 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Bacterial Proteins
• Imidazoles
• Pyridines
• Streptolysins
• plY protein, Streptococcus pneumoniae
• Extracellular Signal-Regulated MAP Kinases
• Mitogen-Activated Protein Kinases
• p38 Mitogen-Activated Protein Kinases
• Caspases
• SB 203580

Topics

• Apoptosis (drug effects)
• Bacterial Proteins (pharmacology)
• Caspases (metabolism)
• Cell Proliferation (drug effects)
• Cell Shape (drug effects)
• Cell Survival (drug effects)
• Enzyme Activation (drug effects)
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Human Umbilical Vein Endothelial Cells (cytology, drug effects, enzymology, ultrastructure)
• Humans
• Imidazoles (pharmacology)
• Mitogen-Activated Protein Kinases (metabolism)
• Phosphorylation (drug effects)
• Pyridines (pharmacology)
• Streptolysins (pharmacology)
• p38 Mitogen-Activated Protein Kinases (antagonists & inhibitors, metabolism)