Elevated Levels of Protein Carbonylation in Patients With Diabetic Nephropathy: Therapeutic and Diagnostic Prospects

Abstract

Background: Oxidative stress-induced protein oxidation has been reported in diabetes mellitus; however a relationship between protein carbonylation and diabetic nephropathy remains to be determined. This study was undertaken to investigate a correlation between protein carbonylation and diabetic nephropathy. Methods: Sera from 153 patients with diabetic nephropathy and 142 healthy humans were selected and protein carbonylation was compared. The glycated hemoglobin (HbA1C), postprandial blood glucose (PPBG), disease duration (DD) and serum creatinine were analyzed and were correlated with the levels of protein oxidation. Results: Protein carbonylation was more pronounced in patients with diabetic nephropathy as compared with healthy humans (P < 0.001). The data showed a positive correlation between protein oxidation and HbA1C (P < 0.001, r = 0.752); the carbonylation was high in those patients with high HbA1C (P < 0.01). The data also showed an important correlation between protein oxidation and PPBG (P < 0.0001, r = 0.680); the carbonyl contents were higher in those patients with higher PPBG (P < 0.001). Results also pointed out a positive correlation of protein oxidation with patients DD (P < 0.001, r = 0.769). Importantly, elevated levels of carbonylation in patients with diabetic nephropathy were also correlated with the elevated levels of serum creatinine. Conclusions: This is the first study that shows a positive correlation between protein carbonylation and diabetic nephropathy. The higher carbonylation in patients with higher HbA1C, blood glucose, DD or serum creatinine indicate that oxidative modifications in proteins play a key role in the progression of diabetic nephropathy.