the effect of inhibition of ca2independent phospholipase a2 on chemotherapeuticinduced death and phospholipid profiles in renal cells we demonstrate that cells derived from primary cultures of rabbit proximal tubules rptc human embryonic kidney hek293 and human kidney carcinomas caki1 express microsomal ca2independent phospholipase a2 ipla2gamma and cytosolic ca2independent phospholipase a2 ipla2beta inhibition of ipla2 activity in these cells using the ipla2 inhibitor bromoenol lactone bel 050microm for 24h did not induce cell death as determined by annexin v and propidium iodide pi staining however bel treatment prior to cisplatin 50mum or vincristine 2microm exposure reduced apoptosis 3050 in all cells tested rptc hek293 and caki1 cells to identify the phospholipids altered during cell death electrospray ionizationmass spectrometry and lipidomic analysis of hek293 and caki1 cells was performed cisplatin treatment reduced 140160 and 160160 phosphatidylcholine ptdcho 50 and 35 respectively in both cell lines 160182 ptdcho in caki1 cells and increased 161226 plasmenylcholine plscho bel treatment prior to cisplatin exposure further decreased 140160 ptdcho 160161 plscho and 160181 plscho in hek293 cells and inhibited cisplatininduced increases in 161226 plscho in caki1 cells treatment of cells with bel prior to cisplatin exposure also increased the levels of several arachidonic containing phospholipids including 160204 181204 and 180204 ptdcho compared to cisplatin only treated cells these data demonstrate that inhibition of ipla2 protects against chemotherapeuticinduced cell death in multiple human renal cell models identifies specific phospholipids whose levels are altered during cell death and demonstrates that alterations in these phospholipids correlate to the protection against cell death in the presence of ipla2 inhibitors