A mathematical model of caspase function in apoptosis
A mathematical model of caspase function in apoptosis
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DOI：
10.1038/77589
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发表时间：
2000-07-01
影响因子：
46.9
通讯作者：
Varner, J
中科院分区：
文献类型：
--
作者：
Fussenegger, M;Bailey, JE;Varner, J
半胱天冬酶（含半胱氨酸的谷氨酸特异性蛋白酶）是细胞自杀机制的核心。这些酶一旦被激活，就通过选择性地切割天冬氨酸残基后的关键蛋白质来分解细胞。由于其在癌症、神经退行性疾病和自身免疫性疾病中的作用，导致半胱天冬酶激活的事件是密集研究的主题。在这里，我们提出了一个机械的数学模型，制定了新出现的信息的基础上，描述受体介导的和应激诱导的caspase激活的关键要素。我们已经使用质量守恒原理结合动力学速率定律，制定常微分方程，描述caspase激活的时间演变。定性的预防caspase激活的策略进行模拟和实验数据进行比较。我们表明，模型预测与现有的信息是一致的。因此，该模型可以帮助更好地理解半胱天冬酶激活和确定促进或延缓凋亡细胞死亡的治疗方法。
Caspases (cysteine-containing aspartate-specific proteases) are at the core of the cell's suicide machinery. These enzymes, once activated, dismantle the cell by selectively cleaving key proteins after aspartate residues. The events culminating in caspase activation are the subject of intense study because of their role in cancer, and neurodegenerative and autoimmune disorders. Here we present a mechanistic mathematical model, formulated on the basis of newly emerging information, describing key elements of receptor-mediated and stress-induced caspase activation. We have used mass-conservation principles in conjunction with kinetic rate laws to formulate ordinary differential equations that describe the temporal evolution of caspase activation. Qualitative strategies for the prevention of caspase activation are simulated and compared with experimental data. We show that model predictions are consistent with available information. Thus, the model could aid in better understanding caspase activation and identifying therapeutic approaches promoting or retarding apoptotic cell death.