Mechanisms of death induced by cisplatin in proximal tubular epithelial cells: Apoptosis vs. necrosis
Mechanisms of death induced by cisplatin in proximal tubular epithelial cells: Apoptosis vs. necrosis
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DOI：
10.1152/ajprenal.1996.270.4.f700
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发表时间：
1996-04-01
期刊：
影响因子：
--
通讯作者：
Levine, J
中科院分区：
文献类型：
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作者：
Lieberthal, W;Triaca, V;Levine, J
我们研究了顺铂诱导的小鼠近端肾小管细胞原代培养细胞死亡的机制。高浓度的顺铂（800 μ M）导致坏死细胞死亡超过几个小时。低得多浓度的顺铂（8 μ M）导致细胞凋亡，这导致损失的细胞单层数天。坏死的特点是胞质肿胀和质膜完整性的早期损失。相反，经历凋亡的细胞的早期特征包括细胞皱缩和与单层的附着丧失。核染色质浓缩，分裂细胞。这些特征在坏死细胞中不存在。暴露于800 μ M顺铂的细胞的DNA电泳由于随机DNA降解而产生“涂片"图案。相反，凋亡细胞的DNA表现出由核小体间DNA切割产生的“梯状"模式。抗氧化剂延迟顺铂诱导的细胞凋亡，但不是坏死。因此，顺铂诱导的细胞死亡机制是浓度依赖性的。活性氧在顺铂诱导的细胞凋亡中起作用，但在顺铂诱导的细胞坏死中不起作用。
We have examined the mechanisms of cell death induced by cisplatin in primary cultures of mouse proximal tubular cells. High concentrations of cisplatin (800 mu M) led to necrotic cell death over a few hours. Much lower concentrations of cisplatin (8 mu M) led to apoptosis, which caused loss of the cell monolayer over several days. Necrosis was characterized by cytosolic swelling and early loss of plasma membrane integrity. In contrast, early features of cells undergoing apoptosis included cell shrinkage and loss of attachment to the monolayer. Nuclear chromatin became condensed and fragmented in apoptosing cells. These features were absent in necrotic cells. DNA electrophoresis of cells exposed to 800 mu M cisplatin yielded a ''smear'' pattern, due to random DNA degradation. In contrast, the DNA of apoptosing cells demonstrated a ''ladder'' pattern resulting from internucleosomal DNA cleavage. Antioxidants delayed cisplatin-induced apoptosis but not necrosis. Thus the mechanism of cell death induced by cisplatin is concentration dependent. Reactive oxygen species play a role in mediating apoptosis but not necrosis induced by cisplatin.