Altered proteasome function and subunit composition in aged muscle
Altered proteasome function and subunit composition in aged muscle
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DOI：
10.1016/j.abb.2003.10.010
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发表时间：
2004-01-01
影响因子：
3.9
通讯作者：
Ferrington, DA
中科院分区：
文献类型：
--
作者：
Husom, AD;Peters, EA;Ferrington, DA
肌原纤维蛋白降解是通过泛素-蛋白酶体途径介导的。为了研究蛋白酶体活性的改变是否在与年龄相关的肌肉萎缩中发挥作用，我们检查了年轻和老年 F344BN 大鼠的肌肉大小和蛋白酶体功能。比目鱼肌中 I 型纤维横截面积减少 38%，证实了与年龄相关的显着肌肉萎缩。蛋白酶体功能的测定表明荧光肽的水解在不同年龄之间是相同的。然而，当考虑到衰老肌肉中 20S 催化核心含量增加 3 倍时，较低的比活性表明随着衰老，单个蛋白质的功能丧失。比较催化 β 亚基的组成显示，细胞因子诱导亚基 LMP2 和 LMP7 与年龄相关，增加了 4 倍。此外，相对于20S蛋白酶体，激活复合物PA28和PA700的含量减少了50%。这些结果表明，老化肌肉中 PA28 和 PA700 的内在活性、免疫蛋白酶体百分比以及 20S 蛋白酶体的调节发生了显着变化。 (C) 2003 Elsevier Inc. 保留所有权利。
Myofibrillar protein degradation is mediated through the ubiquitin-proteasome pathway. To investigate if altered proteasome activity plays a role in age-related muscle atrophy, we examined muscle size and proteasome function in young and aged F344BN rats. Significant age-related muscle atrophy was confirmed by the 38% decrease in cross-sectional area of type I fibers in soleus muscle. Determination of proteasome function showed hydrolysis of fluorogenic peptides was equivalent between ages. However, when accounting for the 3-fold increase in content of the 20S catalytic core in aged muscle, the lower specific activity suggests a functional loss in individual proteins with aging. Comparing the composition of the catalytic beta-subunits showed an age-related 4-fold increase in the cytokine-inducible subunits, LMP2 and LMP7. Additionally, the content of the activating complexes, PA28 and PA700, relative to the 20S proteasome was reduced 50%. These results suggest significant alterations in the intrinsic activity, the percentage of immunoproteasome, and the regulation of the 20S proteasome by PA28 and PA700 in aged muscle. (C) 2003 Elsevier Inc. All rights reserved.