Relevance of oxidative and carbonyl stress to long-term uremic complications.
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.
Molecular and Cellular Nephrology, Institute of Medical Sciences, and Department of Medicine, Tokai University School of Medicine, Isehara, Japan. t-miyata@is.icc.u-tokai.ac.jp
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van Ypersele de Strihou
D000686:Amyloidosis / Q000209:etiology; D001161:Arteriosclerosis / Q000209:etiology; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology*; D014511:Uremia / Q000150:complications* / Q000378:metabolism*
D017127:Glycation End Products, Advanced