title: Cardiac damage and dysfunction in diabetic cardiomyopathy are ameliorated by Grx1.
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.
authors.affiliation: Department of Clinical Biochemistry, Qiqihar Medical University, Heilongjiang, Qiqihar, China.
authors.forename: X
authors.initials: X
authors.lastname: Qi
authors.affiliation: Undergraduate Program of Qiqihar Medical University, Heilongjiang, Qiqihar, China.
authors.forename: A
authors.initials: A
authors.lastname: Xu
authors.affiliation: Clinical Laboratory of Third Affiliated Hospital, Qiqihar Medical University, Heilongjiang, Qiqihar, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Biochemistry, Qiqihar Medical University, Heilongjiang, Qiqihar, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Department of Clinical Biochemistry, Qiqihar Medical University, Heilongjiang, Qiqihar, China.
authors.forename: X
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Biochemistry, Qiqihar Medical University, Heilongjiang, Qiqihar, China.
authors.forename: J
authors.initials: J
authors.lastname: Xu
authors.affiliation: First Affiliated Hospital, Qiqihar Medical University, Heilongjiang, Qiqihar, China.
authors.forename: J
authors.initials: J
authors.lastname: Liu
authors.affiliation: Undergraduate Program of Qiqihar Medical University, Heilongjiang, Qiqihar, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Lan
authors.affiliation: Undergraduate Program of Qiqihar Medical University, Heilongjiang, Qiqihar, China.
authors.forename: L
authors.initials: L
authors.lastname: Chang
authors.affiliation: Department of Biochemistry, Qiqihar Medical University, Heilongjiang, Qiqihar, China cjzhang2005@163.com.
authors.forename: C
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Biology Genetics, Qiqihar Medical University, Heilongjiang, Qiqihar, China.
authors.forename: H
authors.initials: H
authors.lastname: Yu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000201:enzymology / Q000473:pathology; D058065:Diabetic Cardiomyopathies / Q000097:blood / Q000201:enzymology* / Q000473:pathology; D054477:Glutaredoxins / Q000097:blood / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D006321:Heart / Q000503:physiopathology; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D061251:Primary Cell Culture; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D054477:Glutaredoxins; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D020782:Matrix Metalloproteinases; D005978:Glutathione; D019803:Glutathione Disulfide