ABSTRACT. Glutaredoxin 1 (Grx1) has been found to be an important endogenous antioxidant enzyme closely related to the pathogenesis of diabetes and cardiovascular diseases caused by oxidative stress. In this study, the functional changes of the Grx1 redox system in blood of hyperglycemic patients were examined. Furthermore, using a rat model of streptozotocin (STZ)-and high-fat-diet-induced type 2 diabetes, we explored the correlation between functional changes of the Grx1 redox system in the left ventricular tissue and blood of the diabetic rats. Moreover, we studied the protective effect of Grx1 against cardiac toxicity caused by the high-glucose-induced expression of cardiac matrix metalloproteinases (MMPs) in primary cultured cardiac fibroblasts. Finally, we investigated the protective effects and signaling regulatory mechanism of Grx1 against diabetic cardiomyopathy (DCM) in terms of oxidative stress and NF-kB-mediated fibrosis-associated signaling pathways. In the serum of hyperglycemic patients, Grx1 levels were elevated, total/protein thiol or sulfhydryl (Total-SH/P-SH) levels were decreased, glutathione was downregulated, and oxidized glutathione was upregulated. In addition, in the left ventricular myocardium and blood of the diabetic rats, Grx1 levels were significantly increased and glutathione reductase and P-SH levels were decreased. Moreover, endogenous Grx1 was highly expressed in cardiac fibroblasts during high-glucose treatment, and exogenous Grx1 can prevent DCM by controlling oxidative damage and MMP expression. These findings are suggestive of changes in the Grx1 redox system, and Grx1-regulated protein oxidative modifications may serve as molecular markers for diabetes caused by high-glucose-induced oxidative stress.
Abstract. To investigate endogenous carnosine, glutathione system and oxidative stress levels in serum of patients with diabetic cardiomyopathy, and analyze relationships among endogenous carnosine, glutathione system and oxidative stress of patients with diabetic cardiomyopathy. The serum of 68 healthy people (NC), 75 patients with type 2 diabetes mellitus (DM) and 57 patients with diabetic cardiomyopathy (DCM) of the third affiliated hospital of QiQihar Medical University were collected. Carnosine content was measured by ELISA. T-GSH, GSH and GSSG were measured by micro-enzyme labeling. Clinical datas were compared: In comparison to NC group, BMI, FPG, 2hPG,C peptide and HbA1c in the DCM group and DM group increased significantly (P<0.05). The average value of human serum carnosine content, GSH content, GSH/GSSG ratio in the DM and DCM group were significantly lower than that in the control one (P<0.05). Serum endogenous antioxidant peptides and reduced glutathione (GSH) level drop and the imbalance of redox state in diabetic cardiomyopathy patients, which promote the occurrence and development of diabetic cardiomyopathy.
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