Chronic ethanol feeding affects proteasome-interacting proteins.
Chronic ethanol feeding affects proteasome-interacting proteins.
复制标题
DOI：
10.1002/pmic.200800959
复制
发表时间：
2009-07
期刊：
影响因子：
3.4
通讯作者：
Bardag-Gorce, Fawzia
中科院分区：
文献类型：
--
作者：
Bousquet-Dubouch, Marie-Pierre;Nguen, Sheila;Bouyssie, David;Burlet-Schiltz, Odile;French, Samuel W.;Monsarrat, Bernard;Bardag-Gorce, Fawzia
对酒精性肝损伤机制的研究表明，酒精对蛋白酶体活性有明显的抑制作用。为了研究这一现象，我们从长期喂食乙醇的大鼠的肝脏和成对喂食的对照组的肝脏中分离出蛋白酶体复合物，使用非变性多重离心程序来保存蛋白酶体相互作用蛋白（PIPs）。同位素编码亲和标记（ICAT）和MS/MS光谱计数，进一步通过Western blot证实，表明在分离的乙醇蛋白酶体中，几种pip的水平显著降低。这是PA28α/β蛋白酶体激活因子亚基，以及三种蛋白酶体相关的去泛素酶，Rpn11，泛素c端水解酶14 （Usp14）和泛素羧基端水解酶L5 （UCHL5）的情况。有趣的是，在乙醇蛋白酶体部分中缺少Rpn13 c端，这可能改变了UCHL5与蛋白酶体的连接。然而，20S蛋白酶体和大多数19S亚基没有改变，但在分离的乙醇蛋白酶体中，稳定20S与其激活剂之间相互作用的蛋白质Ecm29减少了。有人提出，乙醇代谢通过几种机制引起蛋白酶体抑制，包括改变蛋白酶体相互作用蛋白和与蛋白酶体结合的蛋白酶体调节复合物。
Studies on alcoholic liver injury mechanisms show a significant inhibition of the proteasome activity. To investigate this phenomenon, we isolated proteasome complexes from the liver of rats fed ethanol chronically, and from the liver of their pair-fed controls, using a non-denaturing multiple centrifugations procedure to preserve Proteasome Interacting Proteins (PIPs). Isotope-Coded Affinity Tagging (ICAT) and MS/MS spectral counting, further confirmed by Western blot, showed that the levels of several PIPs were significantly decreased in the isolated ethanol proteasome fractions. This was the case of PA28α/β proteasome activator subunits, and of three proteasome-associated deubiquitinases, Rpn11, ubiquitin C-terminal hydrolase 14 (Usp14), and ubiquitin carboxyl-terminal hydrolase L5 (UCHL5). Interestingly, Rpn13 C-terminal end was missing in the ethanol proteasome fraction, which probably altered the linking of UCHL5 to the proteasome. 20S proteasome and most 19S subunits were however not changed but Ecm29, a protein known to stabilize the interactions between the 20S and its activators, was decreased in the isolated ethanol proteasome fractions. It is proposed that ethanol metabolism causes proteasome inhibition by several mechanisms, including by altering proteasome interacting proteins and proteasome regulatory complexes binding to the proteasome.
登录
查看更多内容
影响因子：
7
作者：
Bousquet-Dubouch, Marie-Pierre;Baudelet, Emilie;Monsarrat, Bernard
通讯作者：
Monsarrat, Bernard
影响因子：
7
作者：
Claverol, S;Burlet-Schiltz, O;Monsarrat, B
通讯作者：
Monsarrat, B
DOI：
10.1111/j.1530-0277.2001.tb02400.x
发表时间：
2001-05-01
影响因子：
3.2
作者：
French, SW;Mayer, RJ;Higashitsuji, H
通讯作者：
Higashitsuji, H
影响因子：
13.5
作者：
Joshi-Barve, S;Barve, SS;McClain, CJ
通讯作者：
McClain, CJ
影响因子：
7.4
作者：
Castegna, A;Aksenov, M;Butterfield, DA
通讯作者：
Butterfield, DA