Apoptosis and necrosis in the liver.
Apoptosis and necrosis in the liver.
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DOI：
10.1002/cphy.c120020
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发表时间：
2013-04
影响因子：
5.8
通讯作者：
Gores GJ
中科院分区：
文献类型：
--
作者：
Guicciardi ME;Malhi H;Mott JL;Gores GJ
由于其独特的功能和解剖位置，肝脏暴露于多种毒素和外来物质，包括药物和酒精，以及嗜肝病毒的感染，因此非常容易受到组织损伤。肝细胞死亡主要通过细胞凋亡或坏死发生，细胞凋亡也是清除受损或感染细胞、维持组织内环境平衡的生理途径。肝细胞，特别是肝细胞和胆管细胞，由于死亡受体在器官中的普遍表达，特别容易受到死亡受体介导的细胞凋亡的影响。以一种非常独特的方式，死亡受体诱导的这些细胞的凋亡是由线粒体和溶酶体通透性共同介导的。内质网和线粒体之间的信号传递促进了肝细胞的凋亡，以应对代谢综合征期间过量的游离脂肪酸生成。这些细胞死亡途径部分受microRNAs调控。肝脏坏死通常与急性损伤(即缺血/再灌注损伤)有关，长期以来一直被认为是一个不受监管的过程。最近，一种新的“程序性”坏死(称为坏死性下垂)被描述：坏死性下垂在肝脏中的作用还有待研究。然而，这一过程中的一个关键角色在肝脏中的最低表达表明，这种形式的细胞死亡在肝病中可能并不常见。由于细胞凋亡是许多肝脏疾病的关键特征，因此对肝细胞死亡的治疗调节是有希望的。本文给出了这些概念的最新概述。
Because of its unique function and anatomical location, the liver is exposed to a multitude of toxins and xenobiotics, including medications and alcohol, as well as to infection by hepatotropic viruses, and therefore, is highly susceptible to tissue injury. Cell death in the liver occurs mainly by apoptosis or necrosis, with apoptosis also being the physiologic route to eliminate damaged or infected cells and to maintain tissue homeostasis. Liver cells, especially hepatocytes and cholangiocytes, are particularly susceptible to death receptor-mediated apoptosis, given the ubiquitous expression of the death receptors in the organ. In a quite unique way, death receptor-induced apoptosis in these cells is mediated by both mitochondrial and lysosomal permeabilization. Signaling between the endoplasmic reticulum and the mitochondria promotes hepatocyte apoptosis in response to excessive free fatty acid generation during the metabolic syndrome. These cell death pathways are partially regulated by microRNAs. Necrosis in the liver is generally associated with acute injury (i.e., ischemia/reperfusion injury) and has been long considered an unregulated process. Recently, a new form of “programmed” necrosis (named necroptosis) has been described: the role of necroptosis in the liver has yet to be explored. However, the minimal expression of a key player in this process in the liver suggests this form of cell death may be uncommon in liver diseases. Because apoptosis is a key feature of so many diseases of the liver, therapeutic modulation of liver cell death holds promise. An updated overview of these concepts is given in this article.
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影响因子：
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影响因子：
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作者：
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