Acrolein-induced cell death: a caspase-influenced decision between apoptosis and oncosis/necrosis
Acrolein-induced cell death: a caspase-influenced decision between apoptosis and oncosis/necrosis
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DOI：
10.1016/s0009-2797(01)00295-2
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发表时间：
2002-01-22
影响因子：
5.1
通讯作者：
Kehrer, JP
中科院分区：
文献类型：
--
作者：
Kern, JC;Kehrer, JP
由于半胱天冬酶在凋亡级联中发挥的主导作用，它们的活性似乎是死亡途径（凋亡与胀亡/坏死）决定中的主要因素。在小鼠FL5.12 proB淋巴细胞中，丙烯醛处理的细胞后果包括缺乏典型的凋亡特征，而不是胀亡/坏死。通过检测细胞内ATP浓度降低、质膜渗漏增加（通过LDH释放和碘化丙啶摄取的流式细胞术检测测量）和形态学标准，胀亡/坏死是明显的。丙烯醛处理的细胞裂解物或重组半胱天冬酶的分析显示半胱天冬酶-3、-8和-9活性的总体剂量依赖性降低。除了丙烯醛对细胞内半胱天冬酶的影响外，它还能够改变由依托泊苷二次治疗或细胞因子撤药诱导的半胱天冬酶依赖性细胞凋亡。丙烯醛在大于或等于20 μ M的剂量下可避免依托泊苷或白细胞介素-3戒断诱导的细胞凋亡。当丙烯醛与氮芥（另一种不依赖于半胱天冬酶的细胞死亡信号传导的烷化剂）组合时，坏死以剂量依赖性方式增加。总之，这些数据表明，半胱天冬酶抑制在细胞死亡途径决定中起重要作用，特别是依赖于半胱天冬酶级联反应诱导细胞凋亡的治疗。(C)2002爱思唯尔科学爱尔兰有限公司保留所有权利。
Due to the dominating roles that caspases play in the apoptotic cascade, their activities appear to be a primary factor in the death pathway (apoptosis versus oncosis/necrosis) decision. In murine FL5.12 proB lymphocytes, the cellular consequences of acrolein treatment included a lack of typical apoptotic features in preference to oncosis/necrosis. Oncosis/necrosis was apparent by detection of a reduction in intracellular ATP concentration, increased plasma membrane leakage (measured by LDH release and flow cytometric detection of propidium iodide uptake) and morphological criteria. Analysis of acrolein-treated cell lysates or recombinant caspase enzymes showed overall dose-dependent decreases in caspase-3, -8 and -9 activities. In addition to acrolein's effect on intracellular caspases, it was also able to alter caspase-dependent apoptosis induced by secondary treatment with etoposide or following cytokine withdrawal. Acrolein at doses greater than or equal to20 muM circumvented etoposide or interleukin-3 withdrawal induced apoptosis. When acrolein was combined with mechlorethamine, another alkylating agent not dependent on caspases for its cell death signaling, necrosis was increased in a dose-dependent manner. Overall, these data suggest that caspase inhibition plays an important role in the cell death pathway decision, particularly with treatments dependent on the caspase cascade to induce apoptosis. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.