Mechanisms of liver cell injury
Mechanisms of liver cell injury
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DOI：
10.1016/s0168-8278(00)80414-6
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发表时间：
2000-01-01
影响因子：
25.7
通讯作者：
Kaplowitz, N
中科院分区：
文献类型：
--
作者：
Kaplowitz, N
肝细胞死亡是由外部环境或细胞内的大量损伤引发的。这些损伤可能使细胞表面受体与死亡结构域结合，导致涉及启动子和执行子半胱天冬酶的蛋白水解级联反应和凋亡死亡。或者，损伤可能会严重破坏线粒体功能，导致体内平衡丧失，伴随着水解酶的激活和坏死或抒情性死亡。细胞凋亡和坏死性细胞死亡的区别最近变得模糊，因为认识到相同的刺激可以诱导细胞死亡以及caspase独立的细胞凋亡。线粒体在细胞死亡的形态中起关键作用;介质的选择性释放放大了凋亡程序并且线粒体功能的严重丧失导致坏死，活性氧代谢产物和一氧化氮作为起始因子和调节剂参与。近年来获得的关于细胞死亡机制的广泛知识无疑将导致肝脏疾病预防和治疗的新的和令人兴奋的进展。重要的靶点包括死亡受体、死亡信号传导机制、线粒体通透性转换和选择性抑制或激活实质细胞与非实质细胞中细胞死亡的方法。
Liver cell death is triggered by a number of insults arising from the external environment or from within the cell. These insults may engage cell surface receptors with death domaines leading to a proteolytic cascade involving initiator and executioner caspases and an apoptotic demise. Alternatively, the insults may profoundly disrupt mitochondrial function and result in loss of homeostasis accompanied by activation of hydrolases and a necrotic or lyric demise. The distinction between apoptotic and necrotic cell death has become blurred recently by the recognition that the same stimuli can induce either form of cell, death as well as caspase independent apoptosis, Mitochondria play a key role in the shape of cell death; selective release of mediators amplifies the apoptosis program and profound loss of mitochondrial function leads to necrosis, Reactive oxygen metabolites and nitric oxide participate as intitiating factors and modulators. The extensive knowledge gained in recent years about the mechanisms of cell death will undoubtedly lead to new and exciting advances in the prevention and treatment of liver diseases. Important targets include death receptors, death signaling mechanisms, the mitochondrial permeability transition and approaches which selectively inhibit or activate cell death in parenchymal versus nonparenchymal cells.