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Modifications in P62 occur due to proteasome inhibition in alcoholic liver disease.

机译:P62的修饰由于酒精性肝病中蛋白酶体的抑制而发生。

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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.
机译:P62能够通过其泛素相关结构域(UBA)结合靶向蛋白质的蛋白酶体降解的多泛素链。酒精性肝炎对人肝中肝细胞的免疫染色显示泛素和P62在Mallory体内共定位。共聚焦显微镜显示,大鼠长期喂食乙醇,其对照组显示P62与蛋白酶体在肝细胞中共定位。 P62与从对照和酒精喂养的大鼠肝脏分离的26S蛋白酶体共沉淀。当饲喂乙醇的大鼠中的蛋白酶体胰凝乳蛋白酶样(ChT-L)活性降低时,P62在26S蛋白酶体部分中增加。使用PS-341(一种有效的蛋白酶体抑制剂)将蛋白酶体的抑制作用与乙醇进料时的抑制作用进行比较。在给予PS-341的大鼠的纯化蛋白酶体部分中,P62蛋白水平也增加了。该数据表明,由于实验性酒精性肝病中的蛋白酶体抑制作用,P62发生了修饰。

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