Miyata T, Kurokawa K, van Ypersele de Strihou C
Molecular and Cellular Nephrology, Institute of Medical Sciences, and Department of Medicine, Tokai University School of Medicine, Isehara, Japan.
Kidney Int Suppl. 2000 Aug;76:S120-5. doi: 10.1046/j.1523-1755.2000.07615.x.
Oxidative stress is a disturbance of balance between oxidants and antioxidant species. The existence of an increased oxidative stress in chronic renal failure is supported by evidence of increased lipid, carbohydrate, and protein oxidation products in plasma and cell membrane. Recent studies have implicated the oxidative stress in the nonenzymatic biochemistry leading to irreversible protein modifications. Reactive oxygen species may directly alter proteins with the eventual formation of oxidized amino acids. Alternatively, reactive carbonyl compounds formed by the oxidation of carbohydrates and lipids may indirectly lead to advanced glycation or lipoxidation of proteins. Chronic uremia is associated with increased modification of protein caused by reactive carbonyl compounds derived from both carbohydrates and lipids. Increased carbonyl modification of proteins subsequently results in the rise of plasma and tissue contents of advanced glycation end products and advanced lipoxidation end products, in which the deleterious biological effects have been revealed. This article focuses on the irreversible nonenzymatic modification of proteins, which might, at least in part, contribute to the development of complications associated with chronic renal failure and long-term dialysis, such as atherosclerosis and dialysis-related amyloidosis.
氧化应激是氧化剂与抗氧化剂之间平衡的紊乱。慢性肾衰竭中氧化应激增加的存在得到了血浆和细胞膜中脂质、碳水化合物和蛋白质氧化产物增加的证据支持。最近的研究表明氧化应激参与了导致蛋白质不可逆修饰的非酶生物化学过程。活性氧可能直接改变蛋白质，最终形成氧化氨基酸。另外，由碳水化合物和脂质氧化形成的活性羰基化合物可能间接导致蛋白质的晚期糖基化或脂氧化。慢性尿毒症与碳水化合物和脂质衍生的活性羰基化合物引起的蛋白质修饰增加有关。蛋白质羰基修饰增加随后导致晚期糖基化终产物和晚期脂氧化终产物的血浆和组织含量升高，其中已揭示了有害的生物学效应。本文重点关注蛋白质的不可逆非酶修饰，这可能至少部分导致与慢性肾衰竭和长期透析相关的并发症的发生，如动脉粥样硬化和透析相关淀粉样变。
