Höhn Annika, Jung Tobias, Grune Tilman
Department of Nutritional Toxicology, Institute of Nutrition, Friedrich-Schiller-University Jena, 07743 Jena, Germany.
Department of Nutritional Toxicology, Institute of Nutrition, Friedrich-Schiller-University Jena, 07743 Jena, Germany.
Free Radic Biol Med. 2014 Jun;71:70-89. doi: 10.1016/j.freeradbiomed.2014.02.028. Epub 2014 Mar 12.
Reactive oxygen species (ROS) are formed continuously in the organism even under physiological conditions. If the level of ROS in cells exceeds the cellular defense capacity, components such as RNA/DNA, lipids, and proteins are damaged and modified, thus affecting the functionality of organelles as well. Proteins are especially prominent targets of various modifications such as oxidation, glycation, or conjugation with products of lipid peroxidation, leading to the alteration of their biological function, nonspecific interactions, and the production of high-molecular-weight protein aggregates. To ensure the maintenance of cellular functions, two proteolytic systems are responsible for the removal of oxidized and modified proteins, especially the proteasome and organelles, mainly the autophagy-lysosomal systems. Furthermore, increased protein oxidation and oxidation-dependent impairment of proteolytic systems lead to an accumulation of oxidized proteins and finally to the formation of nondegradable protein aggregates. Accordingly, the cellular homeostasis cannot be maintained and the cellular metabolism is negatively affected. Here we address the current knowledge of protein aggregation during oxidative stress, aging, and disease.
即使在生理条件下，活性氧（ROS）也会在生物体内持续生成。如果细胞内ROS水平超过细胞防御能力，RNA/DNA、脂质和蛋白质等成分就会受到损伤和修饰，进而影响细胞器的功能。蛋白质尤其容易受到各种修饰的影响，如氧化、糖基化或与脂质过氧化产物结合，从而导致其生物学功能改变、非特异性相互作用以及高分子量蛋白质聚集体的产生。为确保细胞功能的维持，两种蛋白水解系统负责清除氧化和修饰的蛋白质，特别是蛋白酶体和细胞器，主要是自噬-溶酶体系统。此外，蛋白质氧化增加以及蛋白水解系统的氧化依赖性损伤会导致氧化蛋白质的积累，最终形成不可降解的蛋白质聚集体。因此，细胞稳态无法维持，细胞代谢受到负面影响。在此，我们阐述了当前关于氧化应激、衰老和疾病过程中蛋白质聚集的知识。
