[Cardiac cell injury induced by lysophosphatidylcholine].
Lysophosphatidylcholine (LPC) is an amphiphilic metabolite produced from membrane-phospholipids by the activation of phospholipase A2 (PLA2), and it accumulates in the ischemic myocardium. It has been demonstrated that exogenous LPC produces an increase in intracellular Ca2+ concentration ([Ca2+]i), morphological change from rod- to round-shape, and increase in release of creatine kinase (CK). The possible mechanism of the Ca2+ overload induced by LPC is direct Ca2+ entry via a nonselective cation channel (or pore) or secondary Ca2+ entry via Na(+)-Ca2+ exchanger after increase in intracellular Na+ concentration. Among anti-ischemic drugs including beta-adrenoceptor antagonists and Ca2+ channel blockers, a drug with high lipophilicity attenuates the LPC-induced cellular damage, probably due to the preservation of membrane integrity. Because LPC, which accumulates during ischemia and reperfusion of the heart, and produces Ca2+ overload, it is possible that LPC potentiates the ischemic injury in the heart. Therefore, development of protective drugs against cell injury induced by LPC would represent a new approach to finding new drugs that protect the heart against ischemic injury.
Hashizume
H
H
Department of Pharmacology, Asahikawa Medical College, Japan.
Abiko
Y
Y
D000818:Animals; D002118:Calcium / Q000378:metabolism; D006801:Humans; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D017202:Myocardial Ischemia / Q000473:pathology*; D009206:Myocardium / Q000473:pathology*; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2
D008244:Lysophosphatidylcholines; D010741:Phospholipases A; D054467:Phospholipases A2; D002118:Calcium