Contrasting effects of phosphatidylinositol- and phosphatidylcholine-specific phospholipase C on apoptosis in cultured endothelial cells

Endothelium. 2006 May-Jun;13(3):205-11. doi: 10.1080/10623320600760423.

Abstract

In the authors' previous studies, they found that phosphatidylcholine-specific phospholipase C (PC-PLC) and phosphatidylinositol-specific phospholipase C (PI-PLC) played contrary roles in the apoptosis of vascular endothelial cells (VECs), but the mechanism underlying the phenomenon remains unclear. To address this question, in this study, the authors investigated the changes of cell cycle distribution, the expression of P53, and the phosphorylation of Akt when PI-PLC was inhibited by its specific inhibitor compound 48/80, and they also examined the phosphorylation of Akt when VEC apoptosis was inhibited by D609, a specific inhibitor of PC-PLC. The results showed that suppression of PI-PLC promoted VEC apoptosis by inhibiting Akt phosphorylation, elevating P53 expression, and affecting the cell cycle distribution. Contrarily, suppression of PC-PLC promoted the phosphorylation of Akt. The data suggested that PI-PLC and PC-PLC might control the apoptosis by jointly regulating Akt phosphorylation, P53 expression, and affecting cell cycle in VECs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis* / drug effects
  • Bridged-Ring Compounds / pharmacology
  • Cattle
  • Cell Cycle / drug effects
  • Cells, Cultured
  • Endothelial Cells / cytology*
  • Endothelial Cells / enzymology
  • Fibroblast Growth Factors / metabolism
  • Humans
  • Norbornanes
  • Phosphatidylinositol Diacylglycerol-Lyase / antagonists & inhibitors
  • Phosphatidylinositol Diacylglycerol-Lyase / metabolism*
  • Phosphoinositide Phospholipase C
  • Phosphorylation / drug effects
  • Proto-Oncogene Proteins c-akt / metabolism
  • Thiocarbamates
  • Thiones / pharmacology
  • Tumor Suppressor Protein p53 / metabolism
  • Type C Phospholipases / antagonists & inhibitors
  • Type C Phospholipases / metabolism*
  • Umbilical Veins / cytology
  • p-Methoxy-N-methylphenethylamine / pharmacology

Substances

  • Bridged-Ring Compounds
  • Norbornanes
  • Thiocarbamates
  • Thiones
  • Tumor Suppressor Protein p53
  • p-Methoxy-N-methylphenethylamine
  • tricyclodecane-9-yl-xanthogenate
  • Fibroblast Growth Factors
  • Proto-Oncogene Proteins c-akt
  • Type C Phospholipases
  • Phosphoinositide Phospholipase C
  • phosphatidylcholine-specific phospholipase C
  • Phosphatidylinositol Diacylglycerol-Lyase