Chen M, Xiao C Y, Hashizume H, Abiko Y
Department of Pharmacology, Asahikawa Medical College, Nishikagura 4-5, Asahikawa 078-8510, Japan.
Am J Physiol. 1998 Nov;275(5):H1782-7. doi: 10.1152/ajpheart.1998.275.5.H1782.
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.
溶血磷脂酰胆碱（LPC）已知会增加细胞内钙离子浓度（[Ca2+]i），从而导致细胞损伤。在本研究中，我们检测了LPC是否激活磷脂酶A2（PLA2），以及PLA2的激活是否是LPC诱导离体大鼠心肌细胞损伤的原因。LPC（15微摩尔）使[Ca2+]i增加，细胞形状从杆状变为圆形，并伴有肌酸激酶（CK）释放，同时细胞内非酯化脂肪酸（NEFA）水平显著升高，尤其是花生四烯酸。三种PLA2抑制剂，7,7-二甲基-（5Z,8Z）-二十碳二烯酸（DEDA）、3-（4-十八烷基苯甲酰基）丙烯酸（OBAA）和 manoalide，对LPC诱导的不饱和NEFA积累的抑制程度相似。然而，虽然DEDA和OBAA都减弱了LPC诱导的[Ca2+]i增加、细胞形状改变和CK释放，但manoalide对这些均无抑制作用。在无钙溶液中，LPC不会增加[Ca2+]i，NEFA积累也显著减少，但它会使细胞形状从杆状变为圆形，并增加CK释放。这些结果表明，外源性LPC增加了PLA2活性，然而，这可能不是LPC诱导心肌细胞损伤的原因。
