title: Role of calcium/calmodulin signaling pathway in Vibrio vulnificus cytolysin-induced hyperpermeability.
abstract: Endothelial hyperpermeability, a hallmark of septicemia, is induced by stress fiber formation, which is primarily regulated by the calcium/calmodulin signaling pathway in endothelial cells. We previously reported that trifluoperazine, a calcium/calmodulin antagonist, blocks Vibrio vulnificus cytolysin (VVC) -induced lethality at in vivo animal model. The object of this study was therefore to examine whether VVC induces stress fiber formation through calcium/calmodulin signaling in endothelial cells. Here, we monitored calcium-influx after treatment of VVC using confocal microscopy in CPAE cells, pulmonary endothelial cell line. Interestingly, we found that VVC-induced dose-dependently increases of [Ca(2+)](i) in CPAE cells. Moreover, VVC-induced stress fiber formation as well as phosphorylation of myosin light chain (MLC) in a dose- and time-dependent manner, which was completely blocked by trifluoperazine. These results suggest that the calcium/calmodulin signaling pathway plays a pivotal role in VVC-induced hyperpermeability.
authors.affiliation: Department of Biochemistry, Institute for Medical Sciences, Chonbuk National University Medical School, Jeonju, Republic of Korea.
authors.forename: Kwang-Hyun
authors.initials: KH
authors.lastname: Park
authors.forename: Young-Rae
authors.initials: YR
authors.lastname: Lee
authors.forename: Hyeon
authors.initials: H
authors.lastname: Hur
authors.forename: Hong-Nu
authors.initials: HN
authors.lastname: Yu
authors.forename: So-Young
authors.initials: SY
authors.lastname: Rah
authors.forename: Uh-Hyun
authors.initials: UH
authors.lastname: Kim
authors.forename: Kang-Yeol
authors.initials: KY
authors.lastname: Yu
authors.forename: Chan-Moon
authors.initials: CM
authors.lastname: Jin
authors.forename: Myung-Kwan
authors.initials: MK
authors.lastname: Han
authors.forename: Jong-Suk
authors.initials: JS
authors.lastname: Kim
mesh_terms: D000818:Animals; D001427:Bacterial Toxins / Q000633:toxicity*; D002118:Calcium / Q000378:metabolism*; D002147:Calmodulin / Q000378:metabolism*; D002417:Cattle; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000187:drug effects*; D042783:Endothelial Cells / Q000382:microbiology; D018994:Myosin Light Chains / Q000378:metabolism; D054353:Perforin / Q000633:toxicity*; D010766:Phosphorylation; D015398:Signal Transduction / Q000187:drug effects*; D022502:Stress Fibers / Q000378:metabolism; D041261:Vibrio vulnificus / Q000502:physiology*
chemical_list: D001427:Bacterial Toxins; D002147:Calmodulin; D018994:Myosin Light Chains; D054353:Perforin; D002118:Calcium