Lysophosphatidylcholine Inhibits Cardiolipin Biosynthesis in H9c2 Cardiac Myoblast Cells

The effect of phospholipase A2treatment on cardiolipin biosynthesis was investigated in intact H9c2 cardiac myoblasts. Treatment of cells withNaja mocambique mocambiquephospholipase A2reduced the pool sizes of phosphatidylcholine and phosphatidylethanolamine compared with controls. The pool sizes of lysophosphatidylcholine and lysophosphatidylethanolamine were elevated, whereas the pool sizes of cardiolipin and other phospholipids were unaffected by phospholipase A2treatment. Pulse labeling experiments with [1,3-3H]glycerol and pulse-chase labeling experiments with [1,3-3H]glycerol were performed in cells incubated or preincubated in the absence or presence of phospholipase A2. In all experiments, radioactivity incorporated into cardiolipin was reduced in phospholipase A2-treated cells with time compared with controls, indicating attenuatedde novobiosynthesis of cardiolipin. The mechanism for the reduction in cardiolipin biosynthesis in phospholipase A2-treated cells was a decrease in the activity of phosphatidic acid:cytidine-5′-triphosphate cytidylyltransferase, the rate-limiting enzyme of cardiolipin biosynthesis, mediated by elevated cellular lysophosphatidylcholine levels. The results suggest thatde novocardiolipin biosynthesis in H9c2 cells may be regulated by the cellular level of lysophosphatidylcholine.