Sulfiredoxin involved in the protection of peroxiredoxins against hyperoxidation in the early hyperglycaemia
Sulfiredoxin involved in the protection of peroxiredoxins against hyperoxidation in the early hyperglycaemia
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DOI：
10.1016/j.yexcr.2017.02.015
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发表时间：
2017-03-15
影响因子：
3.7
通讯作者：
Li, Hong
中科院分区：
文献类型：
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作者：
Shi, Sa;Guo, Yunqiu;Li, Hong
作为高血糖的直接后果，ROS 的过量产生是糖尿病心肌病发病机制的核心。我们假设高葡萄糖 (HG) 的刺激会导致硫氧还蛋白 (Srx) 表达增加，从而通过减少超氧化的过氧化氧还蛋白 (Prxs) 来调节 ROS 信号传导。我们发现，超氧化的 Prxs 在早期阶段最初减少，但在晚期阶段急剧增加，这些变化对应于糖尿病大鼠心脏中 Srx 表达的显着增加。这些时间依赖性变化也在用 HG 处理的新生儿心肌细胞和 H9c2 细胞中得到证实。此外，HG 24 h组超氧化Prxs的减少率大大提高，Srx表达升高。我们的数据还表明，HG 诱导的 AP1 激活和 Srx 表达几乎被 JNK 抑制剂和 N-乙酰半胱氨酸 (NAC) 消除。此外，siRNA-Srx 抑制 HG 诱导的 ANP 和 beta-MHC 基因表达。这些观察结果表明，HG 诱导的 AP1 激活对于心肌细胞中 Srx 的表达和过度氧化的 Prxs 的减少很重要。这种 Srx 诱导可能是糖尿病或高血糖中针对氧化应激的关键代偿保护机制。最有趣的是，过度氧化的 Prxs/Srx 通路可能参与糖尿病的心脏肥大信号传导。
As a direct consequence of hyperglycaemia, the excessive generation of ROS is central to the pathogenesis of diabetic cardiomyopathy. We hypothesize that stimulation of high glucose (HG) results in an increased sulfiredoxin (Srx) expression, which regulates ROS signaling through reducing the hyperoxidized peroxiredoxins (Prxs). We show that hyperoxidized Prxs were initially reduced in the preliminary stage but then dramatically increased in advanced stage and these changes corresponded to a significant increase of Srx expression in the heart of diabetic rats. These time-dependent changes were also confirmed in neonatal cardiomyocytes and H9c2 cells treated with HG. Moreover, the reduction rate of hyperoxidized Prxs was greatly improved in the HG 24 h group, which had an elevated expression of Srx. Our data also show that HG-induced AP1 activation and Srx expression were almost abolished by JNK inhibitor and N-acetylcysteine (NAC). In addition, siRNA-Srx suppressed HG-induced ANP and beta-MHC gene expression. These observations suggest that activation of AP1 induced by HG is important for the expression of Srx and the reduction of hyperoxidized Prxs in cardiomyocytes. This Srx induction maybe is the pivotal compensatory protection mechanism against oxidative stress in diabetes or hyperglycaemia. Most interestingly, hyperoxidized Prxs/Srx pathway may be involved in the cardiac hypertrophy signaling of diabetes.