Sphingomyelinase of Helicobacter pylori-induced cytotoxicity in AGS gastric epithelial cells via activation of JNK kinase.
The aim of this study was to determine whether the Helicobacter pylori-derived sphigomyelinase (SMase) affects the sphingomyelin pathway and growth in AGS epithelial cells. We showed that the exogenous SMase increased the intracellular level of ceramide in AGS cells and led to rapid stimulation of extracellular signal-regulated kinase (ERK) and c-Jun kinase (JNK) activities. Incubation of AGS cells with H. pylori-derived SMase also resulted in suppression of cell growth and a concomitant induction of apoptosis. Data showed that PD98059 (up to 50 microM), an ERK inhibitor, did not affect the cell viability, whereas the cytotoxicity of exogenous SMase was completely blocked by SP600125, a JNK inhibitor at a concentration of 210 nM. We conclude that the activation of the mitogen-activated protein (MAP) kinases in AGS cells by exogenous H. pylori SMase is a major pathway to mediate the cytotoxicity.
Tseng
Hong-Jia
HJ
School of Medical Technology, Chang Gung University, 333 Tao-yuan, Taiwan, ROC.
Chan
Chung-Chuan
CC
Chan
Err-Cheng
EC
D000873:Anthracenes / Q000494:pharmacology; D017209:Apoptosis; D015153:Blotting, Western; D002455:Cell Division; D002470:Cell Survival; D002478:Cells, Cultured; D002518:Ceramides / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000382:microbiology*; D005419:Flavonoids / Q000494:pharmacology; D016480:Helicobacter pylori / Q000201:enzymology*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D050356:Lipid Metabolism; D048670:MAP Kinase Kinase 4; D020935:MAP Kinase Signaling System; D020929:Mitogen-Activated Protein Kinase Kinases / Q000737:chemistry*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D013108:Sphingomyelin Phosphodiesterase / Q000737:chemistry*; D013270:Stomach / Q000382:microbiology*; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases
D000873:Anthracenes; D002518:Ceramides; D004791:Enzyme Inhibitors; D005419:Flavonoids; C432165:pyrazolanthrone; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases; D013108:Sphingomyelin Phosphodiesterase; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one