Taurine chloramine, an oxidant derived from neutrophils, induces apoptosis in human B lymphoma cells through mitochondrial damage
Taurine chloramine, an oxidant derived from neutrophils, induces apoptosis in human B lymphoma cells through mitochondrial damage
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DOI：
10.1074/jbc.m501170200
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发表时间：
2005-06-03
影响因子：
4.8
通讯作者：
Shacter, E
中科院分区：
文献类型：
--
作者：
Klamt, F;Shacter, E
牛磺酸氯胺(TN-Cl)是由活化的中性粒细胞产生的最丰富的化合物之一。与会导致坏死的HOCl2不同，TN-Cl2是一种有效的肿瘤细胞凋亡诱导剂。在这里，我们表明，TN-Cl诱导的人B淋巴瘤细胞的凋亡依赖于氧化剂介导的线粒体损伤、线粒体膜电位的降低和caspase-9的激活。此外，我们发现TN-Cl被细胞摄取并集中在线粒体中，在那里它诱导通透性转换孔的打开和线粒体的肿胀。用TN-Cl处理分离的线粒体时，活性相同，并被通透性转换孔抑制剂bongkrekic酸和环孢菌素A以及巯基还原剂三(2-羧乙基)膦所阻断。这些数据表明，TN-Cl通过直接损伤线粒体而导致细胞凋亡。
Taurine chloramine (TN-Cl) is one of the most abundant compounds generated by activated neutrophils. In contrast to HOCl, which causes necrosis, TN-Cl is a potent inducer of apoptosis in tumor cells. Here we show that the apoptosis induced by TN-Cl in human B lymphoma cells is dependent upon oxidant-mediated mitochondrial damage, a decrease in mitochondrial membrane potential, and caspase-9 activation. Further, we show that TN-Cl is taken up into the cells and is concentrated in the mitochondria, where it induces opening of the permeability transition pore and mitochondrial swelling. Identical activity is seen upon treatment of isolated mitochondria with TN-Cl and is blocked by the permeability transition pore inhibitors bongkrekic acid and cyclosporin A, as well as by the sulfhydryl-reducing agent tris(2-carboxyethyl)-phosphine. The data suggest that TN-Cl causes apoptosis through direct damage to the mitochondria.