Necrosis, a well-orchestrated form of cell demise: Signalling cascades, important mediators and concomitant immune response
Necrosis, a well-orchestrated form of cell demise: Signalling cascades, important mediators and concomitant immune response
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DOI：
10.1016/j.bbabio.2006.06.014
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发表时间：
2006-09-01
影响因子：
4.3
通讯作者：
Vandenabeele, Peter
中科院分区：
文献类型：
--
作者：
Festjens, Nele;Vanden Berghe, Tom;Vandenabeele, Peter
长期以来，坏死被描述为物理化学应激的结果，因此是偶然的和不受控制的。最近，越来越清楚的是，坏死性细胞死亡和半胱天冬酶依赖性细胞凋亡一样受到良好的控制和编程，并且它可能是一种重要的细胞死亡模式，在病理学和生理学上都是相关的。坏死性细胞死亡不是一个充分描述的信号级联的结果，而是在不同细胞水平上几个生化和分子事件之间广泛串扰的结果。最近的数据表明，丝氨酸/苏氨酸激酶RIP 1，其中包含一个死亡结构域，可能作为一个中央启动子。钙和活性氧（ROS）是坏死细胞死亡的传播和执行阶段的主要参与者，直接或间接地引起对蛋白质、脂质和DNA的损伤，最终导致细胞器和细胞完整性的破坏。坏死垂死的细胞通过主动释放炎性细胞因子并在裂解时溢出其内容物来启动促炎信号级联。解开导致坏死细胞死亡的信号级联将使我们能够开发出在某些信号水平上特异性干扰坏死的工具。坏死发生在生理和病理生理过程中，并且能够杀死已经发展出逃避凋亡的策略的肿瘤细胞。因此，坏死的详细知识可以在治疗策略中利用。(c)2006 Elsevier B. V.保留所有权利。
Necrosis has long been described as a consequence of physico-chemical stress and thus accidental and uncontrolled. Recently, it is becoming clear that necrotic cell death is as well controlled and programmed as caspase-dependent apoptosis, and that it may be an important cell death mode that is both pathologically and physiologically relevant. Necrotic cell death is not the result of one well-described signalling cascade but is the consequence of extensive crosstalk between several biochemical and molecular events at different cellular levels. Recent data indicate that serine/threonine kinase RIP1, which contains a death domain, may act as a central initiator. Calcium and reactive oxygen species (ROS) are main players during the propagation and execution phases of necrotic cell death, directly or indirectly provoking damage to proteins, lipids and DNA, which culminates in disruption of organelle and cell integrity. Necrotically dying cells initiate pro-inflammatory signalling cascades by actively releasing inflammatory cytokines and by spilling their contents when they lyse. Unravelling the signalling cascades contributing to necrotic cell death will permit us to develop tools to specifically interfere with necrosis at certain levels of signalling. Necrosis occurs in both physiological and pathophysiological processes, and is capable of killing tumour cells that have developed strategies to evade apoptosis. Thus detailed knowledge of necrosis may be exploited in therapeutic strategies. (c) 2006 Elsevier B.V. All rights reserved.