IMPLICATION OF ALTERED REDOX REGULATION BY ANTIOXIDANT ENZYMES IN THEINCREASED PLASMA PENTOSIDINE, AN ADVANCED GLYCATION END-PRODUCT, IN UREMIA

Pentosidine is an advanced glycation end product (AGE) formed during M aillard or browning reaction by non-enzymatic glycation and oxidation (glycoxidation). Recent studies demonstrated the increased plasma pent osidine levels not only in diabetic patients with hyperglycemia but al so in normoglycemic uremic patients. The mechanism of increased glycox idation reaction in uremia, however, remains unknown. As superoxide di smutases (SODs) and glutathione peroxidase (GPx) are antioxidant enzym es involved in the metabolism of H2O2 which accelerates the glycoxidat ion reaction, we measured their activities by enzymatic assays in the plasma of normal and non-diabetic hemodialysis patients and examined a link between redox regulation by antioxidant enzymes and glycoxidatio n reaction. The activities of GPx were significantly lower in the plas ma of hemodialysis patients than in normal subjects, whereas those of SODs were higher in the former than in the latter. As plasma SODs comp rise three isozymes, i.e., Cu/Zn-SOD, Mn-SOD, and extracellular (EC)-S OD, we determined the levels of each SOD isozyme by ELISAs. The plasma concentrations of Cu/Zn-SOD and EC-SOD were significantly higher in h emodialysis patients than in normal subjects, whereas those of Mn-SOD did not differ between the two groups. It is of note that GPx activiti es correlated inversely with pentosidine in the plasma of hemodialysis patients (r(2) = 0.262, P < 0.01). There was no significant correlati on between total SOD activities and pentosidine levels in the plasma o f hemodialysis patients, but, among the three SOD isozymes, the plasma EC-SOD levels correlated with the levels of pentosidine in hemodialys is patients (r(2) = 0.286, P < 0.05). As decreased GPx and increased S OD activities result in the increased H2O2 generation, which accelerat es the glycoxidation of protein, these data suggest a link of altered redox regulation by antioxidant enzymes to increased glycoxidation rea ction in the uremic plasma. This paper provides the first time evidenc e for the possible involvement of enzymatic redox regulation in the no n-enzymatic glycoxidation reaction in vivo. (C) 1998 Academic Press.