Activated polymorphonuclear leukocytes induce cardiomyocyte apoptosis and the protective effects of carvedilol.
Activated polymorphonuclear leukocytes induce cardiomyocyte apoptosis and the protective effects of carvedilol.
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DOI：
10.1358/mf.2002.24.7.696541
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发表时间：
2002-09-01
影响因子：
--
通讯作者：
Zhao, ZQ
中科院分区：
文献类型：
--
作者：
Dun, Y;Zhi, JM;Zhao, ZQ
以往的研究表明，缺血和再灌注是诱发心肌细胞凋亡的强有力刺激，并且多形核白细胞（PMNs）参与了缺血和再灌注诱导的心肌损伤的发展。本研究探讨了中性粒细胞是否能直接诱导心肌细胞凋亡，以及其可能的信号转导途径。此外，我们还研究了卡维地洛，一种有效的抗氧化剂，对中性粒细胞诱导的细胞凋亡的影响。将培养的原代新生大鼠心肌细胞暴露于浓度为10（5）、3 × 10（5）和10（6）个细胞/孔的PAF激活的PMN 48 h。应用电镜、DNA凝胶电泳、TUNEL法和流式细胞术等多种检测技术检测心肌细胞凋亡。所有这些技术表明，激活的PMNs直接诱导心肌细胞凋亡的浓度依赖性的方式，而未激活的PMNs显示没有这样的效果。p38-MAPK信号系统特异性抑制剂SB 203580可部分抑制活化PMN诱导的细胞凋亡。卡维地洛（1-10 μ mol/l）可显著抑制激活的PMN_（10）诱导的心肌细胞凋亡。这些结果提示，PMNs激活后可直接诱导心肌细胞凋亡，p38-MAPK信号通路可能参与了这一过程。卡维地洛可能因为其抗氧化特性而阻止PMN诱导的细胞凋亡。(C)普鲁斯·辛斯All rights reserved.
Previous studies have shown that ischemia and reperfusion are potent stimuli for eliciting cardiomyocyte apoptosis, and that polymorphonuclear leukocytes (PMNs) are involved in the development of myocardial injury induced by ischemia and reperfusion. The present study examined whether PMN could directly induce cardiomyocyte apoptosis and, if so, its possible signal transduction pathways. In addition, we also investigated the effects of carvedilol, a potent antioxidant, on PMN-induced apoptosis. Cultured primary neonatal rat cardiomyocytes were exposed to PAF-activated PMNs at concentrations of 10(5), 3 x 10(5) and 10(6) cells/well for 48 h. Multiple detecting techniques, including electron microscopy, DNA gel electrophoresis, TUNEL assay and flow cytometry were used to identify myocyte apoptosis. All of these techniques demonstrated that activated PMNs directly induced cardiomyocyte apoptosis in a concentration-dependent manner, while unactivated PMNs showed no such effect. Activated PMN-induced apoptosis was partially inhibited by SB203580, a specific inhibitor of p38-MAPK signaling system. Carvedilol (at a dose range of 1-10 mumol/l) significantly prevented activated PMN0induced cardiomyocyte apoptosis. These results suggest that PMNs, when activated, directly induce cardiomyocyte apoptosis and thta the p38-MAPK signaling pathway might be involved in this process. Carvedilol may prevent PMN-induced apoptosis because of its antioxidant properties. (C) Prous Scince. All rights reserved.