Oxidative Protein Damage in Plasma of Type 2 Diabetic Patients

Abstract

In this study, we evaluated protein oxidation in 84 patients with Type 2 diabetes with no complications and in 61 healthy volunteers who formed the control group, whose ages matched those of the patients. We determined plasma carbonyl and plasma thiol levels as markers of oxidative protein damage and erythrocyte glutathione, plasma ceruloplasmin and transferrin as markers of free radical scavengers. The concentrations (mean +/- SD) of both of plasma carbonyl (1.24 +/- 0.46 vs. 0.72 +/- 0.17 nmole/mg protein; p < 0.0001) and lipid hydroperoxides (1.8 +/- 0.63 vs. 1.3 +/- 0.21 micromole/l; p < 0.0001) were increased, and the concentration of plasma transferrin (3.85 +/- 0.65 vs. 4.59 +/- 0.79 g/l; p < 0.05) was decreased, respectively, in Type 2 diabetic patients compared with those of the controls. There were no significant differences in the concentrations of plasma thiol (0.0064 +/- 0.001 vs. 0.0068 +/- 0.001 micromole/mg protein), erythrocyte glutathione (2.54 +/- 0.57 vs. 2.65 +/- 0.56 mg/g Hb), plasma ceruloplasmin (548 +/- 107.30 vs. 609 +/- 93.34 mg/l) between the patients and the controls. These changes observed in diabetic patients contribute to the imbalance in the redox status of the plasma. We attribute this imbalance to oxidative protein damage in Type 2 diabetic patients clinically free of complications.

Positive and Negative Regulation of Insulin Signaling by Reactive Oxygen and Nitrogen Species

“…In nearly 3,000 obese persons from the Framingham Heart Study, 8-isoprostane level strongly correlated with body mass index (228). Increase in plasma protein carbonylation, a group of different oxidative protein modifications characterized by various carbonyl moieties, was also reported in both type 1 and 2 diabetes (47,426; reviewed in Ref. 78).…”

“…Accumulation of this group of modifications is considered a marker of One of the most studied irreversible modification is tyrosine nitration, the result of peroxynitrite reaction with the OH moiety in the tyrosine side chain (198,342,434). Along the discussion in section IC, increased total serum protein carbonylation and nitrotyrosine levels have been reported in diabetes (37,50,426), potentially implicating both ROS, RNS, and active carbonyls (like 4-HNE) in systemic protein modification associated with this disorder. In cells, altered protein function occurred in response to in vitro oxidation/nitration.…”

N-acetylcysteine and taurine prevent hyperglycemia-induced insulin resistance in vivo: possible role of oxidative stress

“…Exposure to an elevated glucose concentration of a number of tissues that take up glucose independently of insulin has been shown to result in increased cellular glucose entry and metabolism (15,44,80) and to be associated with oxidative stress (6,15,16,28,33). The latter has been documented by measurement of ROS, e.g., H 2 O 2 (33,37), intracellular concentrations of GSH (reduced glutathione), levels of antioxidant enzymes (glutathione peroxidase, glutathione reductase, and superoxide dismutase), and resultant oxidative changes to protein, lipid, and DNA (6,36,66,82). There is likely more than one mechanism by which increased glucose generates ROS.…”

“…Oxidative stress, which is present in diabetic subjects (6,24,82) and has been suggested to contribute to the complications of diabetes associated with chronic hyperglycemia (6,24), has recently been suggested to induce insulin resistance (64,66). There is evidence to support a link between elevated plasma glucose and oxidative stress.…”

Protective effect of medicinal plant extracts on biomarkers of oxidative stress in erythrocytes

“…The oxidation of GSH to GSSG can dramatically change the GSH/GSSG ratio and consequently the redox status within the cells. As a result, the thiol group of cytosolic proteins is modified by the reversible formation of protein GSH mixed disulfides, a process known as S-glutathionylation (Davies & Goldberg, 1987;Rohn et al, 1998;Di Simplicio et al, 1998;Telci et al, 2000). Due to oxidative stress, polyunsaturated fatty acid of erythrocyte membrane is damaged resulting in a steep increase in malondialdehyde (MDA) concentration, a biomarker currently used for studying oxidation of lipids under different conditions (Pradhan et al, 1990;Konukoglu et al, 1998;Lopez-Revuelta et al, 2005).…”