title: Vibrio vulnificus cytolysin induces apoptosis in HUVEC, SGC-7901 and SMMC-7721 cells via caspase-9/3-dependent pathway.
abstract: Vibrio vulnificus cytolysin (VVC) is known to be a pore-forming toxin which shows cytotoxicity for mammalian cells in culture and induces apoptosis in endothelial cells. In order to determine whether VVC induces apoptosis in vascular endothelial cells and tumor cells, the cytotoxicity induced by recombinant VVC (rVVC) and its potential mechanism in HUVEC, SGC-7901 and SMMC-7721 cells were investigated. Our study demonstrated that rVVC induced the release of intracellular K(+) from all the target cells, yet lactate dehydrogenase was not released by rVVC. It indicates that osmotic lysis might not contribute to the cytolysin-induced cytotoxicity. The study also demonstrated that rVVC induced apoptosis in HUVEC, SGC-7901 and SMMC-7721 cells in time- and dosage-dependent manners, which was associated with the activation of caspase-9 and -3, but not caspase-8. During the apoptotic process of the target cells, rVVC labeled with FITC was monitored to attach initially to the surface of the cells and entered the cytoplasma subsequently. These findings suggest that VVC may be not only a pore-forming toxin, but also a transmembrane toxin with powerful ability to induce apoptosis in human vascular endothelial cells and tumor cells.
authors.affiliation: Basic Medical Microbiology Division, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, Zhejiang, PR China.
authors.forename: Jin-fang
authors.initials: JF
authors.lastname: Zhao
authors.forename: Ai-hua
authors.initials: AH
authors.lastname: Sun
authors.forename: Ping
authors.initials: P
authors.lastname: Ruan
authors.forename: Xu-hong
authors.initials: XH
authors.lastname: Zhao
authors.forename: Miao-quan
authors.initials: MQ
authors.lastname: Lu
authors.forename: Jie
authors.initials: J
authors.lastname: Yan
mesh_terms: D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism*; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000737:chemistry; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003593:Cytoplasm / Q000737:chemistry; D042783:Endothelial Cells / Q000187:drug effects*; D004847:Epithelial Cells / Q000187:drug effects; D022781:Hepatocytes / Q000187:drug effects; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D054353:Perforin / Q000633:toxicity*; D011188:Potassium / Q000378:metabolism; D041261:Vibrio vulnificus / Q000472:pathogenicity*
chemical_list: D054353:Perforin; D007770:L-Lactate Dehydrogenase; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D011188:Potassium