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, phosphatidylcholine-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.
Highlights
The Fas antigen is cell surface protein that mediates apoptosis (Heller and Krönke, 1994; Nagata and Goldstein, 1995)
We investigated to delineate the differential effects of Fas cross-linking on phospholipase D (PLD) activation and sphingolipid metabolism between wild type A20 and three different A20 cells resistant to Fas-induced apoptosis (Fas-resistant A20 cells) which were cloned in our laboratories unexpectedly
To determine the roles of PLD in Fas-induced apoptosis, A20 cells resistant to Fas-induced apoptosis were selected and compared the effect of Fas cross-linking on signaling leading to PLD activation in wild type A20 cells and Fas resistant A20 cells
Summary
The Fas antigen is cell surface protein that mediates apoptosis (Heller and Krönke, 1994; Nagata and Goldstein, 1995). The Fas antigen consists of 319 amino acids (human) or 306 amino acids (mouse) and has similarity to the tumor necrosis factor receptors and lowaffinity nerve growth factor (Itoh et al, 1991; WatanabeFukunaga et al, 1992). Apoptosis induced by Fas activation has been shown to be involved in the regulation of lymphocyte death in the peripheral immune system (Dhein et al, 1995) and T cell-mediated cytotoxicity (Kagi et al, 1994). Engagement of Fas may result in the generation of nonapoptotic signals. Fas has been reported to generate costimulatory signals in lymphocytes (Alderson et al, 1993)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
