Lysophosphatidylcholine accumulation in cardiomyocytes requires thrombin activation of Ca2+-independent PLA2.
Lysophosphatidylcholine accumulation in cardiomyocytes requires thrombin activation of Ca2+-independent PLA2.
复制标题
心肌细胞中溶血磷脂酰胆碱的积累需要凝血酶激活不依赖Ca2+的PLA2。
DOI：
10.1152/ajpheart.1997.272.4.h1972
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发表时间：
1997
期刊：
影响因子：
--
通讯作者：
M. Creer
中科院分区：
文献类型：
--
作者：
J. McHowat;M. Creer
溶血磷脂酰胆碱(LPC)在心肌细胞缺血或凝血酶刺激后积聚。我们确定LPC的积累是通过磷脂酶A2(PLA2)的激活、LPC分解代谢的抑制还是两者的结合来反映LPC产量的增加。凝血酶刺激的常氧心肌细胞LPC含量增加1.5倍，膜相关、非钙依赖的PLA2活性增加2-2.5倍。尽管PLA2被激活，但缺氧本身并不能增加LPC的含量。凝血酶刺激的缺氧性心肌细胞LPC含量增加2.5倍，而PLA2活性没有进一步增加。在常氧和低氧条件下，抑制非钙依赖的PLA2可阻止凝血酶诱导的PLA2活性和LPC含量的增加。药物阻断低氧诱导的LPC分解代谢抑制不影响低氧或凝血酶诱导的PLA2激活或常氧、凝血酶诱导的LPC聚集，但显著降低凝血酶刺激低氧心肌细胞后LPC聚集的幅度。因此，在缺血或凝血酶刺激后LPC的积累完全依赖于PLA2的激活，并通过抑制LPC的分解代谢而进一步增强。
Lysophosphatidylcholine (LPC) accumulates during ischemia or following thrombin stimulation of cardiac myocytes. We determined whether LPC accumulation reflects increased LPC production via phospholipase A2 (PLA2) 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 PLA2 activity. Despite PLA2 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 PLA2 activity. Inhibition of Ca2+-independent PLA2 prevented the thrombin-induced increase in both PLA2 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 PLA2 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 PLA2 activation and further augmented by inhibition of LPC catabolism.