Role of oxidative stress in diabetic complications - A new perspective on an old paradigm
Role of oxidative stress in diabetic complications - A new perspective on an old paradigm
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DOI：
10.2337/diabetes.48.1.1
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发表时间：
1999-01-01
期刊：
影响因子：
7.7
通讯作者：
Thorpe, SR
中科院分区：
文献类型：
--
作者：
Baynes, JW;Thorpe, SR
氧化应激以及对组织的氧化损伤是慢性疾病常见的终点表现，比如动脉粥样硬化、糖尿病和类风湿性关节炎。本综述所探讨的问题是，氧化应激增加在糖尿病并发症的发病机制中是否起主要作用，还是它只是糖尿病终末期组织损伤的一个次要指标。血浆和组织蛋白中糖氧化和脂氧化产物的增加表明糖尿病中氧化应激增强。然而，其中一些产物，比如赖氨酸和精氨酸残基上的3 - 脱氧葡萄糖酮加合物，是独立于氧化化学过程形成的。可氧化底物水平升高也可以解释组织蛋白中糖氧化和脂氧化产物的增加，而无需假定氧化应激增加。此外，经年龄调整后的氧化氨基酸水平（氧化应激更直接的指标）在糖尿病患者的皮肤胶原蛋白中并没有升高。我们提出，糖尿病中碳水化合物和脂质对蛋白质化学修饰的增加是参与活性羰基物质解毒的代谢途径过载的结果，导致由氧化和非氧化反应形成的活性羰基化合物的稳态水平普遍升高。因此，糖尿病中组织蛋白糖氧化和脂氧化的增加可被视为羰基应激增加的结果。本文讨论了氧化应激和羰基应激之间的区别以及这种差异的治疗意义。
Oxidative stress and. oxidative damage to tissues are common end points of chronic diseases, such as atherosclerosis, diabetes, and rheumatoid arthritis. The question addressed in this review is whether increased oxidative stress has a primary role in the pathogenesis of diabetic complications or whether it is a secondary indicator of end-stage tissue damage in diabetes. The increase in glycoxidation and ligoxidation products Ln plasma and tissue proteins suggests that oxidative stress is increased in diabetes. However, some of these products, such as 3-deoxyglucosone adducts to lysine and arginine residues, are formed independent of oxidation chemistry Elevated levels of oxidizable substrates may also explain the increase in glycoxidation and lipoxidation products in tissue proteins, without the necessity of invoking an increase in oxidative stress. Further, age-adjusted levels of oxidized amino acids, a more direct indicator of oxidative stress, are not increased in skin collagen in diabetes. We propose that the increased chemical modification of proteins by carbohydrates and lipids in diabetes is the result of overload on metabolic pathways involved in detoxification of reactive carbonyl species, leading to a general increase in steady-state levels of reactive carbonyl compounds formed by both oxidative and nonoxidative reactions. The increase in glycoxidation and lipoxidation of tissue proteins in diabetes mag therefore be viewed as the result of increased carbonyl stress. The distinction between oxidative and carbonyl stress is discussed along with the therapeutic implications of this difference.