title: Cell death mediated by Vibrio parahaemolyticus type III secretion system 1 is dependent on ERK1/2 MAPK, but independent of caspases.
abstract: Vibrio parahaemolyticus, which causes gastroenteritis, wound infection, and septicemia, has two sets of type III secretion systems (TTSS), TTSS1 and TTSS2. A TTSS1- deficient vcrD1 mutant of V. parahaemolyticus showed an attenuated cytotoxicity against HEp-2 cells, and a significant reduction in mouse lethality, which were both restored by complementation with the intact vcrD1 gene. V. parahaemolyticus also triggered phosphorylation of mitogenactivated protein kinases (MAPKs) including p38 and ERK1/2 in HEp-2 cells. The ability to activate p38 and ERK1/2 was significantly affected in a TTSS1-deficient vcrD1 mutant. Experiments using MAPK inhibitors showed that p38 and ERK1/2 MAPKs are involved in V. parahaemolyticus-induced death of HEp-2 cells. In addition, caspase-3 and caspase-9 were processed into active forms in V. parahaemolyticus-exposed HEp-2 cells, but activation of caspases was not essential for V. parahaemolyticusinduced death of HEp-2 cells, as shown by both annexin V staining and lactate dehydrogenase release assays. We conclude that secreted protein(s) of TTSS1 play an important role in activation of p38 and ERK1/2 in HEp-2 cells that eventually leads to cell death via a caspaseindependent mechanism.
authors.affiliation: Department of Environmental Medical Biology and Institute of Tropical Medicine, The Brain Korea 21 Project, Yonsei University College of Medicine, Seoul 120-752, Korea.
authors.forename: Yu Jin
authors.initials: YJ
authors.lastname: Yang
authors.forename: Na Kyung
authors.initials: NK
authors.lastname: Lee
authors.forename: Na Yeon
authors.initials: NY
authors.lastname: Lee
authors.forename: Jong Woong
authors.initials: JW
authors.lastname: Lee
authors.forename: Soon-Jung
authors.initials: SJ
authors.lastname: Park
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D058947:Bacterial Secretion Systems; D020169:Caspases / Q000378:metabolism*; D016923:Cell Death; D002460:Cell Line; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D051379:Mice; D008813:Mice, Inbred ICR; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D014735:Vibrio Infections / Q000201:enzymology* / Q000382:microbiology / Q000503:physiopathology*; D014736:Vibrio parahaemolyticus / Q000235:genetics / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D058947:Bacterial Secretion Systems; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D020169:Caspases