Gillery Philippe, Jaisson Stéphane, Gorisse Laëtitia, Pietrement Christine
Laboratoire de biologie et de recherche pédiatriques, hôpital Maison Blanche, CHU de Reims, 45, rue Cognacq-Jay, 51092 Reims cedex, France; Laboratoire de biochimie médicale et biologie moléculaire, UMR CNRS/URCA n(o) 7369, faculté de médecine, université de Reims Champagne-Ardenne, 51, rue Cognacq-Jay, 51095 Reims cedex, France.
Laboratoire de biologie et de recherche pédiatriques, hôpital Maison Blanche, CHU de Reims, 45, rue Cognacq-Jay, 51092 Reims cedex, France; Laboratoire de biochimie médicale et biologie moléculaire, UMR CNRS/URCA n(o) 7369, faculté de médecine, université de Reims Champagne-Ardenne, 51, rue Cognacq-Jay, 51095 Reims cedex, France.
Nephrol Ther. 2015 Jun;11(3):129-34. doi: 10.1016/j.nephro.2014.12.004. Epub 2015 Mar 17.
Carbamylation corresponds to the non-enzymatic binding of isocyanic acid, mainly derived from urea decomposition, on amino groups of proteins, and participates in their molecular aging. This process is increased during chronic kidney disease (CKD) because of hyperuremia, and in other pathologies like atherosclerosis, where isocyanic may be formed from thiocyanate by myeloperoxidase in atheroma plates. Carbamylation triggers structural and functional modifications of proteins, thus impairing their biological roles and their interactions with cells. Much experimental evidence in vitro has shown the potential deleterious effects of carbamylated proteins on cell and tissue functions. Carbamylation-derived products (CDPs), and especially their major component homocitrulline, accumulate in organism in long half-life proteins, and may participate in the development of different complications of CKD, especially cardiovascular diseases, renal fibrosis, or nutritional and metabolic troubles. Recent clinical studies have confirmed the link between serum protein carbamylation and morbi-mortality in patients suffering from CKD or undergoing hemodialysis. Some CDPs could be used as biomarkers in these pathologies.
氨甲酰化是指主要由尿素分解产生的异氰酸与蛋白质氨基的非酶结合,并参与其分子老化过程。由于慢性肾病(CKD)时存在高尿素血症,以及在动脉粥样硬化等其他病理状态下(动脉粥样硬化斑块中的髓过氧化物酶可将硫氰酸盐转化为异氰酸),该过程会增强。氨甲酰化会引发蛋白质的结构和功能改变,从而损害其生物学作用及其与细胞的相互作用。许多体外实验证据表明氨甲酰化蛋白质对细胞和组织功能具有潜在有害影响。氨甲酰化衍生产物(CDP),尤其是其主要成分同型瓜氨酸,会在机体的长半衰期蛋白质中蓄积,并可能参与CKD不同并发症的发生发展,尤其是心血管疾病、肾纤维化或营养与代谢紊乱。近期临床研究证实了血清蛋白质氨甲酰化与CKD患者或接受血液透析患者的疾病死亡率之间存在关联。一些CDP可作为这些病理状态下的生物标志物。