Activities and interactions among phospholipases A(2) during thapsigargin-induced S49 cell death

The purpose of this study was to determine the roles of calcium-dependent p hospholipase A(2) (cPLA(2)) and calcium-independent phospholipase A(2) (iPL A(2)) in thapsigargin-induced membrane susceptibility to secretory phosphol ipase A(2) (sPLA(2)) and programmed cell death. H-3-arachidonic acid releas e was observed in the presence of thapsigargin. This release was inhibited partially by an inhibitor of iPLA(2) (BEL) and completely by an inhibitor o f both cPLA(2) and iPLA(2) (MAFP) suggesting that these enzymes were active during apoptosis. The process of cell death did not require the activity o f either enzyme since neither inhibitor impeded the progression of apoptosi s. However, both inhibitors increased the susceptibility of the membrane to sPLA(2) in the presence of thapsigargin. In the case of BEL, this effect a ppeared to involve direct induction of apoptosis in a sub-population of the cells independent of the action of iPLA(2). In conclusion, the results sug gested that cPLA(2) and iPLA(2) are active during thapsigargin-induced apop tosis in S49 cells and that cPLA(2) tempers the tendency of the cells to be come susceptible to sPLA(2) during apoptosis.