d-609 has been researched along with glyceryl-2-arachidonate* in 1 studies
1 other study(ies) available for d-609 and glyceryl-2-arachidonate
Article | Year |
---|---|
Characterization of the lipolytic pathways that mediate free fatty acid release during Fas/CD95-induced apoptosis.
We have undertaken a study to characterize the lipolytic pathway responsible for the generation of free fatty acids (FFA) during Fas/CD95-induced apoptosis in Jurkat cells. It was initially shown that the cellular lipid fraction that suffered the major quantitative decrease during Fas-induced apoptosis was that of phosphatidylcholine (PC). In addition, the secretion of palmitic acid-derived FFA was largely prevented by D609, an inhibitor of PC-specific phospholipase C (PC-PLC) and also by the diacylglycerol lipase (DAGL) inhibitor RHC-80267, suggesting that the secretion of these FFA during Fas-induced apoptosis is mediated by the generation of DAG by a PC-PLC activity and, sequentially, by a 1-DAGL activity which generates the FFA from its sn-1 position. The endocannabinoid 2-arachidonoyl glycerol (2-AG) should be generated as a sub-product of this pathway, but it did not accumulate inside the cells nor was secreted into the supernatant. Interestingly, the complete inhibition of free AA secretion during Fas-induced apoptosis was only achieved by using the AA trifluoromethylketone, which not only inhibits all types of phospholipase-A(2) (PLA(2)) activities, but also the described lytic activities on 2-AG. Using a combination of RHC-80267 and the iPLA(2)-specific inhibitor bromoenol lactone, it was shown that the DAGL pathway also cooperates with iPLA(2) in the generation of free arachidonate. Topics: Apoptosis; Arachidonic Acids; Bridged-Ring Compounds; Cyclohexanones; Endocannabinoids; Enzyme Inhibitors; fas Receptor; Fatty Acids, Nonesterified; Glycerides; Humans; Jurkat Cells; Ketones; Lipid Metabolism; Lipolysis; Lipoprotein Lipase; Models, Biological; Norbornanes; Palmitic Acid; Phosphatidic Acids; Phosphatidylcholines; Thiocarbamates; Thiones; Type C Phospholipases | 2005 |