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 microM) 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+]i with significantly less accumulation of NEFA, but it changed the cell shape from rod to round and increased the release of CK. These results suggest that exogenous LPC increases the PLA2 activity, which, however, may not be responsible for the LPC-induced damage in cardiomyocytes.
Chen
M
M
Department of Pharmacology, Asahikawa Medical College, Nishikagura 4-5, Asahikawa 078-8510, Japan.
Xiao
C Y
CY
Hashizume
H
H
Abiko
Y
Y
D000818:Animals; D002118:Calcium / Q000502:physiology*; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D008244:Lysophosphatidylcholines / Q000633:toxicity*; D008297:Male; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010741:Phospholipases A / Q000502:physiology*; D054467:Phospholipases A2; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects
D005231:Fatty Acids, Unsaturated; D008244:Lysophosphatidylcholines; D010726:Phosphodiesterase Inhibitors; C059778:7,7-dimethyl-5,8-eicosadienoic acid; D010741:Phospholipases A; D054467:Phospholipases A2; D002118:Calcium