Anandamide induces apoptosis in human endothelial cells: its regulation system and clinical implications
Anandamide induces apoptosis in human endothelial cells: its regulation system and clinical implications
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DOI：
10.1055/s-0037-1613475
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发表时间：
2003-05
影响因子：
6.7
通讯作者：
K. Yamaji;K. Sarker;K. Kawahara;S. Iino;M. Yamakuchi;K. Abeyama;T. Hashiguchi;I. Maruyama
中科院分区：
文献类型：
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作者：
K. Yamaji;K. Sarker;K. Kawahara;S. Iino;M. Yamakuchi;K. Abeyama;T. Hashiguchi;I. Maruyama
摘要双胺(AEA)是一种内源性大麻素，由巨噬细胞在休克状态下产生，被认为是感染性休克的致病介质。因此，我们假设AEA在内皮细胞(EC)损伤中起关键作用。在这里，我们证明了AEA以时间和剂量依赖的方式诱导人脐静脉内皮细胞(HUVECs)凋亡。AEA可激活c-jun氨基末端激酶(JNK)和p38丝裂原活化蛋白激酶。AEA还显示白细胞介素1CED-3家族蛋白水解酶(β-3)活性明显升高。AEA诱导的内皮细胞死亡可被选择性香草酸受体1(VR1)拮抗剂Capsazepine抑制，但可被VR1激动剂辣椒素增强，表明AEA通过VR1诱导ECs凋亡。综上所述，我们认为AEA在休克条件下内皮细胞损伤中可能起重要作用，在此条件下使用AEA调节系统的抑制剂可能具有治疗作用。
Summary Anandamide (AEA), an endogenous cannabinoid, is generated by macrophages during shock conditions, and is thought to be a causative mediator of septic shock. Thus, we hypothesized that AEA plays a crucial role in endothelial cell (EC) injury. Here, we demonstrate that AEA induces apoptosis in a time-and dose-dependent manner in human umbilical vein endothelial cells (HUVECs). AEA triggered phosphorylation of c-Jun NH2-terminal kinase (JNK) and p38 mitogen activated protein kinase. AEA also showed a marked increase of interleukin 1β–converting enzyme (ICE)CED-3 family protease (caspase-3) activity. AEA-induced EC death was inhibited by a selective vanilloid receptor 1 (VR1) antagonist, capsazepine, and was enhanced by a VR1 agonist, capsaicin, indicating that AEA induces apoptosis in ECs via VR1. In conclusion, we propose that AEA may play a crucial role in EC injury under conditions of shock, and that the use of inhibitors of the AEA regulation system may have a therapeutic effect under these conditions.