[Ca(2+)]-dependent generation of intracellular reactive oxygen species mediates maitotoxin-induced cellular responses in human umbilical vein endothelial cells.
Maitotoxin (MTX) is known as one of the most potent marine toxins involved in Ciguatera poisoning, but intracellular signaling pathways caused by MTX was not fully understood. Thus, we have investigated whether intracellular reactive oxygen species (ROS) are involved in MTX-induced cellular responses in human umbilical vein endothelial cells. MTX induced a dose-dependent increase of intracellular [Ca(2+)]. MTX stimulated the production of intracellular ROS in a dose- and time-dependent manner, which was suppressed by BAPTA-AM, an intracellular Ca(2+) che-lator. Ionomycin also elevated the ROS production in a dose-dependent manner. MTX elevated transamidation activity in a time-dependent manner and the activation was largely inhibited by transfection of tissue transglutaminase siRNA. The activation of tissue transglutaminase and ERK1/2 by MTX was sup-pressed by BAPTA-AM or ROS scavengers. In addition, MTX-induced cell death was significantly de-layed by BAPTA-AM or a ROS scavenger. These results suggest that [Ca(2+)]-dependent generation of in-tracellular ROS, at least in part, play an important role in MTX-stimulated cellular responses, such as activation of tTGase, ERK phosphorylation, and in-duction of cell death, in human umbilical vein endothelial cells.
Yi
Sun-Ju
SJ
Department of Molecular and Cellular Biochemistry, Kangwon National University College of Medicine, Chunchon 200-701, Korea.
Kim
Kyung Hwan
KH
Choi
Hyun Jung
HJ
Yoo
Je Ok
JO
Jung
Hyo-Il
HI
Han
Jeong-A
JA
Kim
Young-Myeong
YM
Suh
In Bum
IB
Ha
Kwon-Soo
KS
D002118:Calcium / Q000378:metabolism / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors; D006801:Humans; D008387:Marine Toxins / Q000494:pharmacology*; D035964:Oxocins / Q000494:pharmacology*; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013997:Time Factors; D011503:Transglutaminases / Q000037:antagonists & inhibitors; D014471:Umbilical Veins / Q000166:cytology*; D000095702:Polyether Toxins
D002118:Calcium; D048049:Extracellular Signal-Regulated MAP Kinases; D019204:GTP-Binding Proteins; D008387:Marine Toxins; D035964:Oxocins; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D017382:Reactive Oxygen Species; D011503:Transglutaminases; C020394:maitotoxin; D000095702:Polyether Toxins