Suppression of apoptosis by inhibition of phosphatidylcholine-specific phospholipase C in vascular endothelial cells.
In order to clarify the role of phosphatidylcholine-specific phospholipase C (PC-PLC) in the regulation of apoptosis in vascular endothelial cells (VEC), we investigated the effects of D609, a specific inhibitor of PC-PLC, on apoptosis that was induced by deprivation of fibroblast growth factor (FGF) and serum and also by rattlesnake venom. The early morphological changes (detachment of cells from dishes) and the fragmentation of DNA, which is a specific feature of apoptotic cell death, were clearly inhibited by D609 in these two apoptosis-inducing systems. Moreover, the production of diacylglycerol (DAG), which was stimulated in apoptotic VEC, was suppressed by D609. The effects of D609 on the activity of PC-PLC and on apoptosis of VEC were dose-dependent. Our results indicate that PC-PLC is involved in the apoptosis-inducing signal pathway in VEC and, that DAG, produced from phosphatidylcholine (PC), might be an important mediator in this signal-transduction pathway. Our results also suggest that rattlesnake venom, a strong promoter of apoptosis in VEC, might induce apoptosis by stimulating PC-PLC and, furthermore, that PC-PLC might play a significant role in anchorage-dependent signal transduction in VEC.
Miao
J Y
JY
Sugashima Marine Biological Laboratory, School of Science, Nagoya University, Toba, Mie, Japan.
Kaji
K
K
Hayashi
H
H
Araki
S
S
D017209:Apoptosis / Q000187:drug effects*; D001952:Bridged-Ring Compounds / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D003435:Crotalid Venoms / Q000494:pharmacology; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D053938:DNA Fragmentation / Q000187:drug effects; D003864:Depression, Chemical; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D005346:Fibroblast Growth Factors / Q000502:physiology; D006801:Humans; D009636:Norbornanes; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D013859:Thiocarbamates; D013871:Thiones / Q000494:pharmacology*; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors* / Q000502:physiology; D014471:Umbilical Veins
D001952:Bridged-Ring Compounds; D003435:Crotalid Venoms; D016895:Culture Media, Serum-Free; D009636:Norbornanes; D010726:Phosphodiesterase Inhibitors; D013859:Thiocarbamates; D013871:Thiones; C046498:tricyclodecane-9-yl-xanthogenate; D005346:Fibroblast Growth Factors; D010738:Type C Phospholipases; D043265:Phosphatidylinositol Diacylglycerol-Lyase