Oxidative stress inhibits apoptosis in human lymphoma cells
Oxidative stress inhibits apoptosis in human lymphoma cells
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DOI：
10.1074/jbc.274.28.19792
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发表时间：
1999-07-09
影响因子：
4.8
通讯作者：
Shacter, E
中科院分区：
文献类型：
--
作者：
Lee, Y;Shacter, E
细胞凋亡和坏死是在不同条件下诱导的两种细胞死亡形式，在形态和生化特征上存在差异。在本报告中，我们表明，在氧化应激的存在下，人类B淋巴瘤细胞不能进行细胞凋亡，而是以坏死的形式死亡。这是通过化疗药物VP-16或钙离子载体A23187诱导Burkitt淋巴瘤细胞系凋亡，并通过测量凋亡死亡的经典标志物，包括细胞形态、膜联蛋白V结合、DNA阶梯形成和caspase激活来建立的。在较低H2O2浓度（75 ~ 100 μ M）下，VP-16和A23187不能诱导细胞凋亡。相反，细胞发生非凋亡性细胞死亡，伴有轻度细胞质肿胀和核收缩，与单独处理H2O2时观察到的死亡相似。我们发现H2O2通过消耗细胞的ATP来抑制细胞凋亡，H2O2的作用可以被poly(ADP)-核糖基化抑制剂所克服，这也可以保持细胞ATP水平，并且可以被低霉素等抑制ATP合成的药物所模仿。结果表明，氧化剂可以操纵细胞死亡途径，使细胞远离凋亡，这一发现的潜在生理后果将被讨论。
Apoptosis and necrosis are two forms of cell death that are induced under different conditions and that differ in morphological and biochemical features. In this report, we show that, in the presence of oxidative stress, human B lymphoma cells are unable to undergo apoptosis and die instead by a form of necrosis. This was established using the chemotherapy drug VP-16 or the calcium ionophore A23187 to induce apoptosis in Burkitt's lymphoma cell lines and by measuring classical markers of apoptotic death, including cell morphology, annexin V binding, DNA ladder formation, and caspase activation. In the presence of relatively low levels of H2O2 (75-100 mu M), VP-16 and A23187 were unable to induce apoptosis in these cells. Instead, the cells underwent non-apoptotic cell death with mild cytoplasmic swelling and nuclear shrinkage, similar to the death observed when they were treated with H2O2 alone. We found that H2O2 inhibits apoptosis by depleting the cells of ATP, The effects of H2O2 can be overcome by inhibitors of poly(ADP)-ribosylation, which also preserve cellular ATP levels, and can be mimicked by agents such as oligomycin, which inhibit ATP synthesis. The results show that oxidants can manipulate cell death pathways, diverting the cell away from apoptosis, The potential physiological ramifications of this finding will be discussed.