Lysophosphatidylcholine accumulation in cardiomyocytes requires thrombin activation of Ca2+-independent PLA(2)

Lysophosphatidylcholine (LPC) accumulates during ischemia or following thrombin stimulation of cardiac myocytes. mie determined whether LPC accumulation reflects increased LPC production via phospholipase A(2) (PLA(2)) activation, inhibition of LPC catabolism, or a combination of both. Thrombin-stimulated normoxic myocytes demonstrated a 1.5-fold increase in LPC content and a 2- to 2.5-fold increase in membrane-associated, Ca2+-independent PLA(2) activity. Despite PLA(2) activation, hypoxia alone did not increase LPC content. Thrombin-stimulated hypoxic myocytes demonstrated a 2.5-fold increase in LPC content with no further increase in PLA(2) activity. Inhibition of Ca2+-independent PLA(2) prevented the thrombin-induced increase in both PLA(2) activity and LPC content under normoxic and hypoxic conditions. Pharmacological blockade of the hypoxia-induced inhibition of LPC catabolism did not affect hypoxia or thrombin-induced PLA(2) activation or normoxic, thrombin-induced LPC accumulation but greatly diminished the magnitude of LPC accumulation after thrombin stimulation of hypoxic myocytes. Thus accumulation of LPC during ischemia or after thrombin stimulation is absolutely dependent on PLA(2) activation and further augmented by inhibition of LPC catabolism.