Differential roles of proteasome and immunoproteasome regulators Pa28αβ, Pa28γ and Pa200 in the degradation of oxidized proteins.
Differential roles of proteasome and immunoproteasome regulators Pa28αβ, Pa28γ and Pa200 in the degradation of oxidized proteins.
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DOI：
10.1016/j.abb.2012.04.018
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发表时间：
2012-07-15
影响因子：
3.9
通讯作者：
Davies, Kelvin J. A.
中科院分区：
文献类型：
--
作者：
Pickering, Andrew M.;Davies, Kelvin J. A.
关键词：
在小鼠胚胎成纤维细胞 (MEF) 中研究了蛋白酶体调节因子 Pa28αβ（或 11S）、Pa28γ 和 Pa200 在氧化应激适应（也称为毒物兴奋效应）中的反应和功能，使用了对低浓度（1.0 至 10.0μM）过氧化氢 (H2O2) 的良好表征的细胞适应模型，低浓度过氧化氢 (H2O2) 改变了基因表达谱，增加了对高水平氧化应激的抵抗力。 Pa28αβ 在 H2O2 处理后立即与 20S 蛋白酶体结合，而 26S 蛋白酶体同时被分解。在接下来的 24 小时内，Pa28αβ、Pa28γ 和 Pa200 蛋白酶体调节剂的水平在 H2O2 适应过程中增加，而 19S 调节剂的水平没有变化。纯化的 Pa28αβ 以及较小程度的 Pa28γ 显着增强了纯化的 20S 蛋白酶体选择性降解氧化蛋白的能力； Pa28αβ 还增加了纯化的免疫蛋白酶体选择性降解氧化蛋白的能力，但 Pa28γ 却没有。 Pa200 调节剂实际上降低了 20S 蛋白酶体和免疫蛋白酶体降解氧化蛋白质的能力，但 Pa200 和聚 ADP 核糖聚合酶可能协同启动 DNA 修复。我们的结果表明，细胞质 Pa28αβ 和核 Pa28γ 可能都是蛋白酶体降解氧化损伤蛋白质的能力的重要调节因子，并且诱导 20S 蛋白酶体和免疫蛋白酶体的表达，并且它们的 Pa28αβ 和 Pa28γ 调节因子对于氧化应激适应很重要。
The response and functions of proteasome regulators Pa28αβ (or 11S), Pa28γ, and Pa200 in oxidative-stress adaptation (also called hormesis) was studied in murine embryonic fibroblasts (MEF), using a well-characterized model of cellular adaptation to low concentrations (1.0 to 10.0μM) of hydrogen peroxide (H2O2), which alter gene expression profiles, increasing resistance to higher levels of oxidative-stress. Pa28αβ bound to 20S proteasomes immediately upon H2O2-treatment, whereas 26S proteasomes were disassembled at the same time. Over the next 24 hours, the levels of Pa28αβ, Pa28γ, and Pa200 proteasome regulators increased during H2O2-adaptation, whereas the 19S regulator was unchanged. Purified Pa28αβ, and to a lesser extent Pa28γ, significantly increased the ability of purified 20S proteasome to selectively degrade oxidized proteins; Pa28αβ also increased the capacity of purified immunoproteasome to selectively degrade oxidized proteins but Pa28γ did not. Pa200 regulator actually decreased 20S proteasome and immunoproteasome’s ability to degrade oxidized proteins but Pa200 and poly-ADP ribose polymerase may cooperate in enabling initiation of DNA repair. Our results indicate that cytoplasmic Pa28αβ and nuclear Pa28γ may both be important regulators of proteasome’s ability to degrade oxidatively-damaged proteins, and induced-expression of both 20S proteasome and immunoproteasome, and their Pa28αβ and Pa28γ regulators are important for oxidative-stress adaptation.
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