Variations of thioredoxin system contributes to increased susceptibility to apoptosis in cardiomyocytes of type 2 diabetic rats

• Published in: Acta biochimica et biophysica Sinica 2014-04, Vol.46 (4), p.318-329
• Main Authors: Zhao, Xiaoqin, Zhang, Yan, Li, Xiaoyu, Wang, Ruiyuan, Jiao, Xiangying
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Base Sequence; Blotting, Western; caspase-3; Diabetes Mellitus, Experimental - metabolism; Diabetes Mellitus, Experimental - pathology; Diabetes Mellitus, Type 2 - metabolism; Diabetes Mellitus, Type 2 - pathology; DNA Primers; mRNA表达; Myocytes, Cardiac - metabolism; Myocytes, Cardiac - pathology; Rats; Real-Time Polymerase Chain Reaction; RNA, Messenger - genetics; Streptozocin; Thioredoxins - genetics; Thioredoxins - metabolism; 事务处理系统; 心肌细胞凋亡; 易感性; 硫氧还蛋白; 糖尿病大鼠
• ISSN: 1672-9145; 1745-7270
• DOI: 10.1093/abbs/gmu006

Cardiac complications are the leading cause of death in diabetes. However, the mechanism of diabetes in inducing myocardial injury and apoptosis, and whether the thioredoxin （Trx） system is involved remain unclear. In this study, male Sprague-Dawley rats were randomly divided into two groups： the control and the diabetes groups, and then were randomly divided into five different timepoints （the 1st, 2nd, 4th, 12th, and 24th week）. The results showed that diabetes-induced cardiac injury was enhanced in the type 2 diabetes rats, as evidenced by aggravated cardiac dysfunction, biochemical indicators, and increased myocardial apoptosis （TUNEL and caspase-3 activity）. The activity of myocardial Trx and Trx reductase （TR） in diabetic rats was significantly decreased from the second week and continually aggravated with the disease progression. In diabetic rats, the mRNA expression of Trxl, Trx2, TR1, and TR2 was decreased first and then increased after the fourth week. Meanwhile, the protein expression of these Trx system members was significantly increased at the 12th week. Trx nitration was cleared, the Trx/ASK1 interaction was significantly decreased, and the activity of p38 was significantly enhanced in cardiac tissues at the 12th week. These results demonstrated that diabetes may cause myocardial injury and apoptosis, and the extent of which was accompanied with the development of the disease. The mechanism is associated with the development of diabetes and the decreased activity of Trx and TR. The reasons for decreased Trx activity may include： decrease of Trx and TR protein expression; nitration modification of Trx; and up-regulation of TXNIP expression.