Carbonyl stress: increased carbonyl modification of tissue and cellular proteins in uremia.
Advanced glycation end-products (AGEs) are formed during non enzymatic glycation and oxidation (glycoxidation) reactions. This process is accelerated in diabetics owing to hyperglycemia, and it has been implicated in the pathogenesis of diabetic complications. Surprisingly, AGEs increase in normoglycemic uremic patients to a much greater extent than in diabetics. AGE accumulation in uremia cannot be attributed to hyperglycemia nor simply to a decreased removal by glomerular filtration. Recently gathered evidence has suggested that, in uremia, the increased carbonyl compounds derived from carbohydrates and lipids modify proteins not only by glycoxidation reaction but also by lipoxidation reaction ("carbonyl stress"). Carbonyl stress has been implicated in the pathogenesis of long-term uremic complications such as dialysis-related amyloidosis. With regard to continuous ambulatory peritoneal dialysis (CAPD), the peritoneal cavity appears to be in a state of severe overload of carbonyl compounds derived from CAPD solution containing high glucose, from heat sterilization of the solution, and from uremic circulation. Carbonyl stress might modify not only peritoneal matrix proteins and alter their structures, but also react with mesothelial and endothelial cell surface proteins and initiate a range of inflammatory responses. Carbonyl stress might therefore contribute to the development of peritoneal sclerosis in patients with long-term CAPD.
Institute of Medical Sciences and Department of Internal Medicine, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
T
T
Miyata
Y
Y
Izuhara
H
H
Sakai
K
K
Kurokawa
D000447:Aldehydes / Q000378:metabolism; D050260:Carbohydrate Metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D050356:Lipid Metabolism; D015227:Lipid Peroxidation; D008239:Lysine / Q000031:analogs & derivatives / Q000378:metabolism; D018384:Oxidative Stress; D010531:Peritoneal Dialysis, Continuous Ambulatory; D010537:Peritoneum / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D014511:Uremia / Q000378:metabolism* / Q000628:therapy
D000447:Aldehydes; D017127:Glycation End Products, Advanced; D011506:Proteins; C048496:N(6)-carboxymethyllysine; D008239:Lysine