Lysophosphatidylcholine inhibits cardiolipin biosynthesis in H9c2 cardiac myoblast cells.
The effect of phospholipase A2 treatment on cardiolipin biosynthesis was investigated in intact H9c2 cardiac myoblasts. Treatment of cells with Naja mocambique mocambique phospholipase A2 reduced 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 A2 treatment. 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 attenuated de novo biosynthesis 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 that de novo cardiolipin biosynthesis in H9c2 cells may be regulated by the cellular level of lysophosphatidylcholine.
Xu
F Y
FY
Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, Canada.
Taylor
W A
WA
Hatch
G M
GM
D000818:Animals; D002308:Cardiolipins / Q000096:biosynthesis*; D002460:Cell Line; D017815:Elapidae; D005990:Glycerol / Q000378:metabolism; D007700:Kinetics; D008244:Lysophosphatidylcholines / Q000378:metabolism*; D008246:Lysophospholipids / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D010741:Phospholipases A / Q000494:pharmacology*; D054467:Phospholipases A2; D010743:Phospholipids / Q000378:metabolism*; D051381:Rats; D014316:Tritium
D002308:Cardiolipins; D008244:Lysophosphatidylcholines; D008246:Lysophospholipids; D010743:Phospholipids; C008301:lysophosphatidylethanolamine; D014316:Tritium; D010741:Phospholipases A; D054467:Phospholipases A2; D005990:Glycerol