Role of calcium/calmodulin signaling pathway in Vibrio vulnificus cytolysin-induced hyperpermeability.
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.
Park
Kwang-Hyun
KH
Department of Biochemistry, Institute for Medical Sciences, Chonbuk National University Medical School, Jeonju, Republic of Korea.
Lee
Young-Rae
YR
Hur
Hyeon
H
Yu
Hong-Nu
HN
Rah
So-Young
SY
Kim
Uh-Hyun
UH
Yu
Kang-Yeol
KY
Jin
Chan-Moon
CM
Han
Myung-Kwan
MK
Kim
Jong-Suk
JS
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*
D001427:Bacterial Toxins; D002147:Calmodulin; D018994:Myosin Light Chains; D054353:Perforin; D002118:Calcium