Cytotoxic mechanism of Vibrio vulnificus cytolysin in CPAE cells.
Vibrio vulnificus is an estuarian bacterium that causes septicemia and serious wound infection. The cytolysin, one of the important virulence determinants in V. vulnificus infection, has been reported to have lethal activity primarily by increasing pulmonary vascular permeability. In the present study, we investigated the cytotoxic mechanism of V. vulnificus cytolysin in cultured pulmonary artery endothelial (CPAE) cells, which are possible target cells of cytolysin in vivo. V. vulnificus cytolysin caused the CPAE cell damages with elevation of the cytosolic free Ca2+, DNA fragmentation, and decrease of the cellular NAD+ and ATP level. These cytotoxic effects of V. vulnificus cytolysin were prevented by EGTA and aminobenzamide, but were not affected by verapamil or catalase. These results indicate that the elevation of cytosolic free Ca2+ induced by V. vulnificus cytolysin causes the increase of DNA fragmentation and the damaged DNA activates nuclear poly(ADP-ribose) synthetase, which depletes the cellular NAD+ and ATP, resulting in cell death.
Rho
Hye-Won
HW
Department of Biochemistry and Institute for Medical Sciences, Medical School, Chonbuk National University, Chonju, South Korea.
Choi
Min-Ji
MJ
Lee
Ji-Na
JN
Park
Jin-Woo
JW
Kim
Jong-Suk
JS
Park
Byung-Hyun
BH
Sohn
Hee-Sook
HS
Kim
Hyung-Rho
HR
D000255:Adenosine Triphosphate / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D003603:Cytotoxins / Q000633:toxicity*; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009243:NAD / Q000378:metabolism; D011651:Pulmonary Artery / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D014733:Vibrio / Q000472:pathogenicity*
D003603:Cytotoxins; D009243:NAD; D000255:Adenosine Triphosphate; D002118:Calcium