Exp Mol Med.  2002 Jul;34(3):201-210.

Differential effects of Fas cross-linking on phospholipase D activation and related lipid metabolism in Fas-resistant A20 cells.

• Lim SY
• Lee SC
• Shin IC
• Han JS

Abstract

A20 murine lymphoma cells undergoing Fas-mediated apoptosis showed increase in the activity of phospholipase D (PLD), which is involved in proliferative or mitogenic cellular responses. Using A20 cell lines that were resistant to Fas-induced apoptosis, we investigated the differential effects of Fas cross-linking on PLD activity and sphingolipid metabolism. The basal PLD activities in all of the selected three Fas-resistant clones (#5, #8, and #11) were about 2~4 folds higher than that of wild type A20 cells. Among the PLD isoforms, PLD2 expression was increased in all of the selected Fas-resistant clones. The Fas downstream signaling events triggered by Fas cross-linking, including the activations of PLD, phosphatidy-lcholine-specific phospholipase C (PC-PLC), sphingomyelinase (SMase), the increase in diacylglycerol (DAG) and protein phosphorylation levels, and the translocation of protein kinase C to membrane were not changed in both of Fas-resistant clone #5 and #8. In contrast, Fas cross-linking stimulated the activity of PLD, PC-PLC, and SMase, translocation of PKC, and protein phosphorylation in Fas-resistant clone #11, similar to that of wild type cells. We also found that clone #11 had a different Fas sequence encoding Fas B which has been known to inhibit Fas-induced apoptosis. These findings suggest that increased PLD2 expression resulting in increased basal PLD activity and the blockade of Fas downstream signaling cascades may be involved to limit apoptosis induced by Fas cross-linking.

Keyword

Fas; phsopholipase D; phospholipase C; sphingomyelinase; protein kinase C; apoptosis

MeSH Terms

Animals
Antibodies, Monoclonal/immunology/pharmacology
Antigens, CD95/immunology/*metabolism
Base Sequence
Carrier Proteins/metabolism
Clone Cells
Cross-Linking Reagents/pharmacology
Diglycerides/metabolism
Enzyme Activation/drug effects
Lipids/*metabolism
Mice
Molecular Sequence Data
Phospholipase D/*metabolism
Phosphorylation/drug effects
Protein Kinase C/metabolism
*Signal Transduction/drug effects
Sphingomyelin Phosphodiesterase/metabolism
Tumor Cells, Cultured