Serum Levels of S-Glutathionylated Proteins as a Risk-Marker for Arteriosclerosis Obliterans

Abstract

Background Oxidative stress plays a role in the development of chronic peripheral arterial disease (PAD) because under these conditions redox regulation is impaired, inducing the S-glutathionylation of proteins. A method of estimating the levels of S-glutathionylated proteins has been developed using biotinylated glutathione S-transferase, which allows the study of their crucial role in the oxidative stress-related progression of PAD. Methods and ResultsThe serum levels of S-glutathionylated proteins were examined in 41 patients with arteriosclerosis obliterans (ASO) and 38 age-matched non-ASO patients using biotinylated glutathione S-transferase. The levels were higher in the patients with ASO, even early on, and positively correlated with the ankle/brachial index. In vitro, the levels of S-glutathionylated proteins were reduced in the presence of glutathione and glutaredoxin. Conclusions Serum levels of S-glutathionylated proteins are a sensitive risk-marker for ASO at an early stage. (Circ J 2007; 71: 100 -105)

Redox-based regulation of signal transduction: Principles, pitfalls, and promises

“…Steady state levels of Grx itself appear to be dynamically regulated, and increases in Grx occur in cancer and cardiovascular disease [83,103]. Elevated levels of Sglutathionylated proteins in serum have been suggested to represent a risk-marker for arteriosclerosis obliterans [104]. Recent studies from our laboratory (Y J-H) have demonstrated that multiple stimuli, such as the TLR ligands, lipopolysaccharide (LPS) and CpG DNA, interleukin-4, and transforming growth factor-beta 1 (TGF-β1) result in decreases in Grx activity in primary lung epithelial cells, in association with decreases in Grx1 mRNA, in response to TGF-β1 [105].…”

Roles of Oxidative Stress and Redox Regulation in Atherosclerosis

“…We examined levels of S-glutathionylated serum proteins and found an increase in patients with ASO ( Fig. 3) 50) . The data suggest that oxidative stress and a balance of redox regulation play a role in vascular function.…”

Serum S-glutathionylated proteins as a potential biomarker of carotid artery stenosis

“…This antibody also reacted with multiple S-glutathionylated proteins in serum from a CS patient (lane 2) and a patient with arteriosclerosis obliterans who were found to have an increase of serum S-glutathionylated proteins in our previous study [21] (lane 3, the left image in Figure 1B).…”

“…In another study, the S-glutathionylated proteins in serum were found to differ between CS patients and patients with arteriosclerosis obliterans [21]. It will be interesting to determine whether the pattern of S-glutathionylated proteins in serum has disease specificity.…”