Institute of Nutrition, Department of Nutritional Toxicology, Friedrich Schiller University Jena, Germany.
Curr Pharm Des. 2011 Dec 1;17(36):4007-22. doi: 10.2174/138161211798764898.
Living in an oxygen containing environment is automatically connected to oxidative stress. Beside lipids and nucleic acids, especially proteins are very susceptible for oxidative modifications. These oxidative modifications comprise alterations of single amino acids, like the formation of protein carbonyls and methionine sulfoxide, or the aggregation of whole proteins. Due to the ongoing accumulation of protein aggregates during the aging process, the cellular protein quality control system becomes more and more overwhelmed. One essential element of the protein quality control machinery is the ubiquitin proteasomal system which plays therefore a crucial part in the aging process, too. Ubiquitination of proteins is a three step mechanism to tag proteins with a polyubiquitin chain for the proteasome. The proteasome is a regulated, barrel-shaped multi-enzyme complex which is responsible for the degradation of proteins. Although there is no drastic loss of all proteasomal subunits during the aging process, there is a functional decline of the proteasome activity in aging organisms. Impairment of the ubiquitin proteasome system leads to increasing protein aggregation and cellular death. A lot of age related diseases are closely connected to an inhibition of the proteasome and the formation of large protein aggregates. Especially skin aging, atherosclerosis, age-dependent macula degeneration, cataract formation and several neurodegenerative diseases are directly connected to the decline of proteasome function. This review outlines the connections between aging, oxidative stress and protein oxidation, as well as the influence on the ubiquitin proteasomal system and several associated diseases.
生活在含氧环境中会自动导致氧化应激。除了脂质和核酸外，蛋白质尤其容易受到氧化修饰。这些氧化修饰包括单个氨基酸的改变，如蛋白质羰基和蛋氨酸亚砜的形成，或整个蛋白质的聚集。由于在衰老过程中蛋白质聚集体的不断积累，细胞的蛋白质质量控制系统越来越不堪重负。蛋白质质量控制系统的一个重要组成部分是泛素蛋白酶体系统，因此它在衰老过程中也起着至关重要的作用。蛋白质的泛素化是一种将蛋白质标记为多泛素链的三步机制，用于蛋白酶体。蛋白酶体是一种受调控的桶形多酶复合物，负责蛋白质的降解。尽管在衰老过程中并非所有蛋白酶体亚基都明显丢失，但衰老生物体中蛋白酶体的活性会下降。泛素蛋白酶体系统的损伤会导致蛋白质聚集和细胞死亡增加。许多与年龄相关的疾病与蛋白酶体的抑制和大蛋白质聚集体的形成密切相关。特别是皮肤衰老、动脉粥样硬化、年龄相关性黄斑变性、白内障形成和几种神经退行性疾病都与蛋白酶体功能的下降直接相关。这篇综述概述了衰老、氧化应激和蛋白质氧化之间的联系，以及对泛素蛋白酶体系统和几种相关疾病的影响。
