Phospholipase A2 is not responsible for lysophosphatidylcholine-induced damage in cardiomyocytes

Lysophosphatidylcholine (LPC) is known to increase the intracellular concentration of Ca2+([Ca2+]i), leading to cell damage. In the present study we examined whether LPC activates phospholipase A2(PLA2) and whether the activation of PLA2 is responsible for the LPC-induced cell damage in isolated rat cardiomyocytes. LPC (15 μM) produced an increase in [Ca2+]i, a change in cell shape from rod to round, and the release of creatine kinase (CK) accompanied by a significant elevation of the cellular level of nonesterified fatty acids (NEFA), especially arachidonic acid. Three PLA2 inhibitors, 7,7-dimethyl-(5Z,8Z)-eicosadienoic acid (DEDA), 3-(4-octadecylbenzoyl)acrylic acid (OBAA), and manoalide, attenuated the LPC-induced accumulation of unsaturated NEFA to a similar degree. Nevertheless, whereas both DEDA and OBAA attenuated the LPC-induced increase in [Ca2+]i, change in cell shape, and release of CK, manoalide attenuated none of them. In the Ca2+-free solution, LPC did not increase [Ca2+]iwith significantly ...