Activities and interactions among phospholipases A2 during thapsigargin-induced S49 cell death.
The purpose of this study was to determine the roles of calcium-dependent phospholipase A2 (cPLA2) and calcium-independent phospholipase A2 (iPLA2) in thapsigargin-induced membrane susceptibility to secretory phospholipase A2 (sPLA2) and programmed cell death. 3H-arachidonic acid release was observed in the presence of thapsigargin. This release was inhibited partially by an inhibitor of iPLA2 (BEL) and completely by an inhibitor of both cPLA2 and iPLA2 (MAFP) suggesting that these enzymes were active during apoptosis. The process of cell death did not require the activity of either enzyme since neither inhibitor impeded the progression of apoptosis. However, both inhibitors increased the susceptibility of the membrane to sPLA2 in the presence of thapsigargin. In the case of BEL, this effect appeared to involve direct induction of apoptosis in a sub-population of the cells independent of the action of iPLA2. In conclusion, the results suggested that cPLA2 and iPLA2 are active during thapsigargin-induced apoptosis in S49 cells and that cPLA2 tempers the tendency of the cells to become susceptible to sPLA2 during apoptosis.
Wilson
H A
HA
Department of Zoology, Brigham, Young University, Provo, Utah 84602, USA.
Allred
D V
DV
O'Neill
K
K
Bell
J D
JD
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D016718:Arachidonic Acid / Q000378:metabolism; D001095:Arachidonic Acids / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D053938:DNA Fragmentation; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008223:Lymphoma; D051379:Mice; D063065:Organophosphonates / Q000494:pharmacology; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000378:metabolism*; D054467:Phospholipases A2; D019284:Thapsigargin / Q000494:pharmacology*; D014316:Tritium / Q000378:metabolism; D014407:Tumor Cells, Cultured
D001095:Arachidonic Acids; D004791:Enzyme Inhibitors; D063065:Organophosphonates; C104810:methyl arachidonylfluorophosphonate; D014316:Tritium; D016718:Arachidonic Acid; D019284:Thapsigargin; D010741:Phospholipases A; D054467:Phospholipases A2