Mallory bodies formed in proteasome-depleted hepatocytes: An immunohistochemical study
Mallory bodies formed in proteasome-depleted hepatocytes: An immunohistochemical study
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DOI：
10.1006/exmp.2000.2343
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发表时间：
2001-02-01
影响因子：
3.6
通讯作者：
French, SW
中科院分区：
文献类型：
--
作者：
Bardag-Gorce, F;French, BA;French, SW
马洛里小体（MB）是蛋白质的聚集体，主要是在肝细胞中发现的细胞角蛋白。它们也存在于一些其他细胞类型中，如II型肺细胞和滋养层细胞。迄今为止，对肝脏的研究表明，MB来源于经历了构象变化的高度磷酸化、高度泛素化的蛋白质。由于蛋白酶体不能从肝细胞的细胞质中去除改变的蛋白质，聚集的蛋白质可能积累。为了研究这种可能性，蛋白酶体在喂食诱导MB形成的药物的小鼠的单个肝细胞中进行了化学方法评估。为了加速和增强MB形成，使用细胞色素P450 2EI敲除小鼠。使用蛋白酶体亚基（P25）的抗体通过免疫荧光观察单个细胞中的蛋白酶体。结果表明，已形成MB的肝细胞群通常部分耗尽蛋白酶体。这些发现支持MB形成的可能性，作为蛋白酶体的损失，以消除错误折叠的细胞角蛋白的结果。因此，MB可能与其他类型的细胞内含物共享其发病机制，其中蛋白质由于突变、错误折叠或蛋白酶体丢失而在细胞质中聚集。(C)北京：科学出版社.
Mallory bodies (MBs) are aggregates of proteins, principally cytokeratin proteins found in liver cells. They are also found in a few other cell types such as type II pneumocytes and trophoblasts. Studies on the liver thus far indicate that MBs are derived from hyperphosphorylated, heavily ubiquitinated proteins which have undergone conformational change. The aggregated protein may accumulate because of the failure of the proteasome to remove the altered proteins from the cytoplasm of liver cells. To investigate this possibility, the proteasomes were assessed immunohistochemically in individual liver cells of mice fed a drug which induced MB formation. To accelerate and enhance MB formation, cytochrome P450 2EI knockout mice were used. Proteasomes in individual cells were visualized by immunofluorescence using an antibody to a subunit of the proteasome (P25). The results showed that the groups of liver cells that had formed MBs were often partially depleted of proteasomes. These findings support the possibility that MBs formed as a result of the loss of the proteasome to remove misfolded cytokeratin proteins. Thus MBs may share their pathogenesis with other types of cellular inclusions seen where proteins aggregate in the cytoplasm due to mutation, misfolding, or loss of proteasomes. (C) 2001 Academic Press.