Modifications in P62 occur due to proteasome inhibition in alcoholic liver disease
Modifications in P62 occur due to proteasome inhibition in alcoholic liver disease
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DOI：
10.1016/j.lfs.2005.04.020
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发表时间：
2005-09-30
期刊：
影响因子：
6.1
通讯作者：
French, SW
中科院分区：
文献类型：
--
作者：
Bardag-Gorce, F;Francis, T;French, SW
P62能够结合多聚泛素链，该多聚泛素链通过其泛素相关结构域（乌巴）靶向蛋白质以被蛋白酶体降解。免疫组化染色显示泛素和P62共定位于马洛里小体。慢性乙醇喂养的大鼠及其对照组的共聚焦显微镜显示，P62与肝细胞中的蛋白酶体共定位。P62与从对照和酒精喂养的大鼠的肝脏分离的26 S蛋白酶体共沉淀。P62在26 S蛋白酶体组分中增加时，蛋白酶体糜蛋白酶样（ChT-L）活性降低，在大鼠喂养乙醇。PS-341，一种有效的蛋白酶体抑制剂，用于比较蛋白酶体的抑制与乙醇进料时发生的抑制。在给予PS-341的大鼠的纯化蛋白酶体组分中，P62蛋白水平也增加。这些数据表明，在实验性酒精性肝病中，由于蛋白酶体抑制而发生P62的修饰。(c)2005年爱思唯尔公司All rights reserved.
P62 is capable of binding the polyubiquitin chain that targets proteins for degradation by the proteasome through its ubiquitin associated domain (UBA). Immunostaining of hepatocytes from human liver with alcoholic hepatitis showed colocalization of ubiquitin and P62 in Mallory bodies. Rats fed ethanol chronically and their controls showed that P62 is colocalized with the proteasome in hepatocytes as shown by confocal microscopy. P62 cosedimented with 26S proteasomes isolated from livers of control and alcohol fed rats. P62 was increased in the 26S proteasome fraction when the proteasome chymotrypsin-like (ChT-L) activity decreased in rats fed ethanol. PS-341, a potent proteasome inhibitor was used to compare the inhibition of the proteasome with the inhibition which occurs with ethanol feeding. P62 protein levels were also increased in the purified proteasome fraction of rats given PS-341. This data indicates that modifications in P62 occur due to proteasome inhibition in experimental alcoholic liver disease. (c) 2005 Elsevier Inc. All rights reserved.