Staphylococcus aureus α-toxin-induced cell death:: predominant necrosis despite apoptotic caspase activation
Staphylococcus aureus α-toxin-induced cell death:: predominant necrosis despite apoptotic caspase activation
复制标题
DOI：
10.1038/sj.cdd.4401301
复制
发表时间：
2003-11-01
影响因子：
12.4
通讯作者：
Jänicke, RU
中科院分区：
文献类型：
--
作者：
Essmann, F;Bantel, H;Jänicke, RU
最近的数据表明，金黄色葡萄球菌的主要溶血素α-毒素通过经典的凋亡途径诱导细胞死亡。然而，在这里，我们证明，虽然zVAD-因子或Bcl-2的过度表达完全废除半胱天冬酶的激活和核小体间DNA片段化，它们并没有显着影响α-毒素诱导的Jurkat T或MCF-7乳腺癌细胞的死亡。半胱天冬酶抑制对α-毒素诱导的乳酸脱氢酶释放和ATP消耗也没有影响。此外，虽然CD 95诱导细胞凋亡的早期评估仅导致产生活性半胱天冬酶阳性的细胞，但这些细胞尚未渗透碘化丙啶，但很大一部分α毒素处理的细胞对活性半胱天冬酶和PI均呈阳性。最后，电子显微镜检查表明，即使在活性半胱天冬酶的存在下，α-毒素处理的细胞显示出坏死的形态，其特征在于细胞肿胀和细胞质空泡化。总之，我们的数据表明，α-毒素诱导的细胞死亡的进展，即使在激活的半胱天冬酶的存在下，至少部分地，在半胱天冬酶独立的，坏死样的方式。
Recent data suggest that alpha-toxin, the major hemolysin of Staphylococcus aureus, induces cell death via the classical apoptotic pathway. Here we demonstrate, however, that although zVAD-fmk or overexpression of Bcl-2 completely abrogated caspase activation and internucleosomal DNA fragmentation, they did not significantly affect alpha-toxin-induced death of Jurkat T or MCF-7 breast carcinoma cells. Caspase inhibition had also no effect on alpha-toxin-induced lactate dehydrogenase release and ATP depletion. Furthermore, whereas early assessment of apoptosis induction by CD95 resulted solely in the generation of cells positive for active caspases that were, however, not yet permeable for propidium iodide, a substantial proportion of alpha-toxin-treated cells were positive for both active caspases and PI. Finally, electron microscopy demonstrated that even in the presence of active caspases, alpha-toxin-treated cells displayed a necrotic morphology characterized by cell swelling and cytoplasmic vacuolation. Together, our data suggest that alpha-toxin-induced cell death proceeds even in the presence of activated caspases, at least partially, in a caspase-independent, necrotic-like manner.