Proteasome function and protein oxidation in the aged retina
Proteasome function and protein oxidation in the aged retina
复制标题
DOI：
10.1006/exer.2002.2022
复制
发表时间：
2002-09-01
影响因子：
3.4
通讯作者：
Ferrington, DA
中科院分区：
文献类型：
--
作者：
Louie, JL;Kapphahn, RJ;Ferrington, DA
蛋白酶体途径负责细胞活力所必需的过程，包括氧化蛋白的选择性降解。在许多组织中已经报道了蛋白酶体功能的年龄依赖性丧失，但尚未在视网膜中进行检查。在这项研究中，我们评估了蛋白酶体功能和蛋白质氧化的视网膜匀浆从年轻的成年和老年F344 BN大鼠。对老年大鼠视网膜蛋白酶体的研究。我们观察到酪蛋白降解速率降低80%，胰凝乳蛋白酶样活性损失75%。这种活性的损失可以部分地由20 S蛋白酶体表达减少50%来解释。调节复合物PA 700和与胰凝乳蛋白酶样活性相关的诱导型β亚基LMP 7在年轻和老年大鼠中以相对于20 S催化核心相同的浓度表达。免疫化学分析使用抗体，识别蛋白质的氧化修饰，硝基酪氨酸和4-羟基-2-壬烯醛，显示视网膜蛋白质从老年大鼠表现出最大的免疫反应性。这些结果表明，与年龄相关的蛋白酶体功能的丧失有助于氧化视网膜蛋白的积累。因此，氧化蛋白的增加和负责去除细胞中氧化蛋白的蛋白酶的失活的组合效应使老化的视网膜处于由氧化应激引起的不可逆损伤的更大风险中。(C)2002 Elsevier Science Ltd.
The proteasomal pathway is responsible for processes essential for cell viability, including the selective degradation of oxidized proteins. An age-dependent loss in proteasome function has been reported in many tissues, but has not been examined in the retina. In this study, we evaluated proteasome function and protein oxidation in retinal homogenates from young adult and old F344BN rats. For retinal proteasome from old rats. we observed an 80% decrease in the rate of casein degradation and a 75% loss in chymotrypsin-like activity. This loss in activity could be partially accounted for by a 50% reduction in expression of the 20S proteasome. The regulatory complex PA700 and the inducible beta-subunit, LMP7, which is associated with the chymotrypsin-like activity, were expressed in equivalent concentrations relative to the 20S catalytic core in both young and old rats. Immunochemical analysis using antibodies that recognize the protein oxidative modifications, nitrotyrosine and 4-hydroxy-2-nonenal, showed that retinal proteins from old rats exhibited the greatest immunoreactivity. These results suggest that the age-related loss in proteasome function contributes to the accumulation of oxidized retinal proteins. Thus, the combined effect of an increase in oxidized proteins and Inactivation of the protease responsible for ridding the cell of oxidized proteins places the aged retina at greater risk for irreversible damage caused by oxidative stress. (C) 2002 Elsevier Science Ltd.