title: Non-hemolytic enterotoxin of Bacillus cereus induces apoptosis in Vero cells.
abstract: Bacillus cereus is an opportunistic pathogen that often causes foodborne infectious diseases and food poisoning. Non-hemolytic enterotoxin (Nhe) is the major toxin found in almost all enteropathogenic B. cereus and B. thuringiensis isolates. However, little is known about the cellular response after Nhe triggered pore formation on cell membrane. Here, we demonstrate that Nhe induced cell cycle arrest at G0/G1phase and provoked apoptosis in Vero cells, most likely associated with mitogen-activated protein kinase (MAPK) and death receptor pathways. The influx of extracellular calcium ions and increased level of reactive oxygen species in cytoplasm were sensed by apoptosis signal-regulating kinase 1 (ASK1) and p38 MAPK. Extrinsic death receptor Fas could also promote the activation of p38 MAPK. Subsequently, ASK1 and p38 MAPK triggered downstream caspase-8 and 3 to initiate apoptosis. Our results clearly demonstrate that ASK1, and Fas-p38 MAPK-mediated caspase-8 dependent pathways are involved in apoptotic cell death provoked by the pore-forming enterotoxin Nhe.
authors.affiliation: Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Veterinary Medicine, China Agricultural University, Beijing, China.|National Center for Veterinary Drug Safety Evaluation, College of Veterinary Medicine, China Agricultural University, Beijing, China.
authors.forename: Xiaoye
authors.initials: X
authors.lastname: Liu
authors.affiliation: National Center for Veterinary Drug Safety Evaluation, College of Veterinary Medicine, China Agricultural University, Beijing, China.
authors.forename: Shuangyang
authors.initials: S
authors.lastname: Ding
authors.affiliation: The Children's Hospital of Fudan University, Shanghai, China.
authors.forename: Peijie
authors.initials: P
authors.lastname: Shi
authors.affiliation: Institute of Food Safety, Department of Veterinary Sciences, Ludwig-Maximilians-University Munich, Oberschleißheim, Germany.
authors.forename: Richard
authors.initials: R
authors.lastname: Dietrich
authors.affiliation: Institute of Food Safety, Department of Veterinary Sciences, Ludwig-Maximilians-University Munich, Oberschleißheim, Germany.
authors.forename: Erwin
authors.initials: E
authors.lastname: Märtlbauer
authors.affiliation: Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Veterinary Medicine, China Agricultural University, Beijing, China.
authors.forename: Kui
authors.initials: K
authors.lastname: Zhu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D001409:Bacillus cereus / Q000502:physiology*; D001427:Bacterial Toxins / Q000494:pharmacology; D020013:Calcium Signaling; D002522:Chlorocebus aethiops; D004768:Enterotoxins / Q000494:pharmacology / Q000502:physiology*; D059585:G1 Phase Cell Cycle Checkpoints; D018384:Oxidative Stress; D053218:Receptors, Death Domain / Q000378:metabolism; D015398:Signal Transduction; D014709:Vero Cells
chemical_list: D001427:Bacterial Toxins; D004768:Enterotoxins; D053218:Receptors, Death Domain
keywords: Bacillus cereus; MAPK pathway; Vero cell; apoptosis; non-hemolytic enterotoxin