Plasma protein thiol oxidation and carbonyl formation in chronic renal failure

被引:202
作者
Himmelfarb, J
McMonagle, E
McMenamin, E
机构
[1] Maine Med Ctr, Div Nephrol, Portland, ME 04102 USA
[2] Maine Med Ctr, Res Inst, Portland, ME USA
关键词
hemodialysis; uremia; oxidant stress; thiol; carbonyl; biocompatibility;
D O I
10.1046/j.1523-1755.2000.00443.x
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Background. Myeloperoxidase-catalyzed oxidative pathways have recently been identified as an important cause of oxidant stress in uremia and hemodialysis (HD), and can lead to plasma protein oxidation. We have examined patterns of plasma protein oxidation in vitro in response to hydrogen peroxide (H2O2) and hypochlorous acid (HOCl). We measured thiol oxidation, amine oxidation, and carbonyl concentrations in patients on chronic maintenance HD compared with patients with chronic renal failure (CRF) and normal volunteers. We have also examined the effect of the dialysis procedure on plasma protein oxidation using biocompatible and bioincompatible membranes. Methods. Plasma proteins were assayed for the level of free thiol groups using spectrophotometry, protein-associated carbonyl groups by enzyme-linked immunosorbent assay, and oxidation of free amine groups using a fluorescent spectrophotometer. Results. In vitro experiments demonstrate HOCl oxidation of thiol groups and increased carbonyl formation. In vivo, there are significant differences in plasma-free thiol groups between normal Volunteers (279 +/- 12 mu mol/L), CRF patients (202 +/- 20 mu mol/L, P = 0.005) and HD patients (178 +/- 18 mu mol/L, P = 0.0001). There are also significant differences in plasma protein carbonyl groups between normal volunteers (0.76 +/- 0.51 mu moI/L), CRF patients (13.73 +/- 4.45 mu mol/L, P = 0.015), and HD patients (16.95 +/- 2.62 mu mol/L, P = 0.0001). There are no significant differences in amine group oxidation. HD with both biocompatible and bioincompatible membranes restored plasma protein thiol groups to normal levels, while minimally affecting plasma protein carbonyl expression. Conclusions. First, both CRF and HD patients have increased plasma protein oxidation manifested by oxidation of thiol groups and formation of carbonyl groups. Second, HD with biocompatible and bioincompatible membranes restored plasma protein thiol groups to normal levels. Third, these experiments suggest that there is a dialyzable low molecular weight toxin found in uremia that is responsible for plasma protein oxidation.
引用
收藏
页码:2571 / 2578
页数:8
相关论文
共 62 条
[31]  
Kaysen GA, 1997, MINER ELECTROL METAB, V23, P218
[32]   Determinants of albumin concentration in hemodialysis patients [J].
Kaysen, GA ;
Stevenson, FT ;
Depner, TA .
AMERICAN JOURNAL OF KIDNEY DISEASES, 1997, 29 (05) :658-668
[33]  
Kaysen GA, 1998, J AM SOC NEPHROL, V9, P2368
[34]  
Kim SB, 1999, PERITON DIALYSIS INT, V19, pS144
[35]   Lipoprotein(a) is a predictor for cardiovascular mortality of hemodialysis patients [J].
Koda, Y ;
Nishi, S ;
Suzuki, M ;
Hirasawa, Y .
KIDNEY INTERNATIONAL, 1999, 56 :S251-S253
[36]   Mass spectrometric quantification of markers for protein oxidation by tyrosyl radical, copper, and hydroxyl radical in low density lipoprotein isolated from human atherosclerotic plaques [J].
Leeuwenburgh, C ;
Rasmussen, JE ;
Hsu, FF ;
Mueller, DM ;
Pennathur, S ;
Heinecke, JW .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (06) :3520-3526
[37]  
LEVINE RL, 1994, METHOD ENZYMOL, V233, P346
[38]  
LOUGHREY CM, 1994, Q J MED, V87, P679
[39]  
LUCIAK M, 1991, NEPHROL DIAL TRANSPL, V6, P66
[40]   ENHANCED LDL OXIDATION IN UREMIC PATIENTS - AN ADDITIONAL MECHANISM FOR ACCELERATED ATHEROSCLEROSIS [J].
MAGGI, E ;
BELLAZZI, R ;
FALASCHI, F ;
FRATTONI, A ;
PERANI, G ;
FINARDI, G ;
GAZO, A ;
NAI, M ;
ROMANINI, D ;
BELLOMO, G .
KIDNEY INTERNATIONAL, 1994, 45 (03) :876-883