Oncosis represents the main type of cell death in mouse models of cholestasis
Oncosis represents the main type of cell death in mouse models of cholestasis
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DOI：
10.1016/j.jhep.2004.10.016
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发表时间：
2005-03-01
影响因子：
25.7
通讯作者：
Denk, H
中科院分区：
文献类型：
--
作者：
Fickert, P;Trauner, M;Denk, H
背景/目标：由于胆汁淤积导致肝细胞死亡的机制还没有很好的定义，我们的目的是获得更深入的了解相关的发病机制的原则。方法：在胆总管结扎（CBDL）和胆酸（CA）喂养的小鼠中评估细胞死亡，并通过研究H和E染色的组织切片、DNA梯状分析、半胱天冬酶-3样活性测定、免疫组织化学、结果：经Jo2处理的小鼠表现出caspase-3的活化、CK中间丝网络的破坏和典型的凋亡形态学特征。相比之下，在CA喂养和CBDL小鼠，细胞肿胀和细胞膜破裂的细胞胀亡的特点是细胞死亡的主要类型，而在这两个实验条件下，caspase-3的显着激活是不存在的，典型的CK改变是罕见的，尽管频繁的阳性TUNEL assay.Conclusions：（i）胀亡的主要类型的肝细胞死亡在小鼠急性胆汁淤积。(ii)如果使用非特异性检测系统（如TUNEL法），可能会高估胆汁淤积中细胞凋亡的重要性。(c)2004年欧洲肝脏研究协会。Elsevier B.V.出版，保留所有权利。
Background/Aims: Since the mechanisms leading to hepatocyte death in cholestasis are not well defined, we aimed to obtain closer insights into the related pathogenetic principles.Methods: Cell death was assessed in common bile duct ligated (CBDL) and cholic acid (CA)-fed mice, and compared to Fas agonist Jo2-injected mice by studying H and E-stained tissue sections, DNA ladder analysis, caspase-3-like activity assay, immunohistochemistry, double immunofluorescence microscopy for activated caspase-3 and cytokeratin (CK) 18, the TUNEL method, and electron microscopy.Results: Jo2-treated mice showed activation of caspase-3, breakdown of the CK intermediate filament network, and classical morphological features of apoptosis. In contrast, in CA-fed and CBDL mice, oncosis characterized by cell swelling and ruptured cell membranes was the predominant type of cell death, whereas in both experimental conditions significant activation of caspase-3 was absent and typical CK alterations were rare despite frequent positivity of the TUNEL assay.Conclusions: (i) Oncosis represents the main type of hepatocyte death in acute cholestasis in mice. (ii) The importance of apoptosis in cholestasis may be overestimated if non-specific detection systems (e.g. TUNEL assay) are used. (c) 2004 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.