Cardiac-specific overexpression of catalase prevents diabetes-induced pathological changes by inhibiting NF-κB signaling activation in the heart
Cardiac-specific overexpression of catalase prevents diabetes-induced pathological changes by inhibiting NF-κB signaling activation in the heart
复制标题
过氧化氢酶的心脏特异性过度表达通过抑制心脏中 NF-κ B 信号传导的激活来预防糖尿病引起的病理变化
DOI：
10.1016/j.yjmcc.2015.10.010
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发表时间：
2015-12-01
影响因子：
5
通讯作者：
Tan, Yi
中科院分区：
文献类型：
--
作者：
Cong, Weitao;Ruan, Dandan;Tan, Yi
过氧化氢酶是一种特异性分解过氧化氢（H2 O2）的抗氧化酶。据报道，通过心脏特异性启动子（CAT-TG）过表达过氧化氢酶可减少糖尿病诱导的活性氧（ROS）积累，并进一步预防糖尿病诱导的病理异常，包括小鼠心脏结构紊乱和左心室舒张。然而，过氧化氢酶过表达保护心脏功能的机制仍不清楚。这项研究发现，在过氧化氢酶过表达的糖尿病小鼠心脏中，ROS依赖性NF-κ B信号通路的激活下调。此外，过氧化氢酶过表达抑制了参与能量代谢的关键酶硝化水平的显著增加，包括α-酮戊二酸脱氢酶E1组分（α-KGD）和ATP合酶α和β亚基（ATP-α和ATP-β）。为了评估NF-κ B通路激活对心脏功能的影响，将NF-κ B信号通路抑制剂Bay 11 -7082注射到糖尿病小鼠中，保护小鼠免受心脏损伤的发展和参与能量代谢的关键酶的硝化修饰的增加。总之，这些研究结果表明，过氧化氢酶保护小鼠心脏免受糖尿病心肌病，部分通过抑制NF-κ B依赖性炎症反应和相关的蛋白质硝化。(C)2015爱思唯尔有限公司版权所有。
Catalase is an antioxidant enzyme that specifically catabolizes hydrogen peroxide (H2O2). Overexpression of catalase via a heart-specific promoter (CAT-TG) was reported to reduce diabetes-induced accumulation of reactive oxygen species (ROS) and further prevent diabetes-induced pathological abnormalities, including cardiac structural derangement and left ventricular abnormity in mice. However, the mechanism by which catalase overexpression protects heart function remains unclear. This study found that activation of a ROS-dependent NF-kappa B signaling pathway was downregulated in hearts of diabetic mice overexpressing catalase. In addition, catalase overexpression inhibited the significant increase in nitration levels of key enzymes involved in energy metabolism, including alpha-oxoglutarate dehydrogenase E1 component (alpha-KGD) and ATP synthase alpha and beta subunits (ATP-alpha and ATP-beta). To assess the effects of the NF-kappa B pathway activation on heart function, Bay11-7082, an inhibitor of the NF-kappa B signaling pathway, was injected into diabetic mice, protecting mice against the development of cardiac damage and increased nitrative modifications of key enzymes involved in energy metabolism. In conclusion, these findings demonstrated that catalase protects mouse hearts against diabetic cardiomyopathy, partially by suppressing NF-kappa B-dependent inflammatory responses and associated protein nitration. (C) 2015 Elsevier Ltd. All rights reserved.