Thioredoxin 2 Offers Protection against Mitochondrial Oxidative Stress in H9c2 Cells and against Myocardial Hypertrophy Induced by Hyperglycemia.
Thioredoxin 2 Offers Protection against Mitochondrial Oxidative Stress in H9c2 Cells and against Myocardial Hypertrophy Induced by Hyperglycemia.
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DOI：
10.3390/ijms18091958
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发表时间：
2017-09-15
影响因子：
5.6
通讯作者：
Shi S
中科院分区：
文献类型：
--
作者：
Li H;Xu C;Li Q;Gao X;Sugano E;Tomita H;Yang L;Shi S
线粒体氧化应激被认为是糖尿病心肌病发展的关键因素。硫氧还蛋白2（Trx 2）是一种线粒体抗氧化剂，其沿着Trx还原酶2（Trx R2）和过氧化物氧还蛋白3（Prx 3），清除H2O2并提供针对氧化应激的保护。我们以前的研究表明，TrxR抑制剂导致Trx2氧化和增加ROS从线粒体的排放。在本研究中，我们观察到TrxR抑制也损害了离体心脏的收缩功能。我们的研究表明，在高糖处理的H9c2心肌细胞和链脲佐菌素（STZ）诱导的糖尿病大鼠心肌中，Trx 2的表达减少。过表达Trx2可显著减轻高糖诱导的H9c2细胞线粒体氧化损伤，提高ATP合成。值得注意的是，Trx2过表达可以抑制高糖诱导的心钠素（ANP）和脑钠素（BNP）基因表达。我们的研究表明，高葡萄糖诱导的线粒体氧化损伤可以通过升高Trx2水平来预防，从而为糖尿病心脏提供广泛的保护。
Mitochondrial oxidative stress is thought to be a key contributor towards the development of diabetic cardiomyopathy. Thioredoxin 2 (Trx2) is a mitochondrial antioxidant that, along with Trx reductase 2 (TrxR2) and peroxiredoxin 3 (Prx3), scavenges H2O2 and offers protection against oxidative stress. Our previous study showed that TrxR inhibitors resulted in Trx2 oxidation and increased ROS emission from mitochondria. In the present study, we observed that TrxR inhibition also impaired the contractile function of isolated heart. Our studies showed a decrease in the expression of Trx2 in the high glucose-treated H9c2 cardiac cells and myocardium of streptozotocin (STZ)-induced diabetic rats. Overexpression of Trx2 could significantly diminish high glucose-induced mitochondrial oxidative damage and improved ATP production in cultured H9c2 cells. Notably, Trx2 overexpression could suppress high glucose-induced atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) gene expression. Our studies suggest that high glucose-induced mitochondrial oxidative damage can be prevented by elevating Trx2 levels, thereby providing extensive protection to the diabetic heart.
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