Cardiac-specific overexpression of catalase attenuates lipopolysaccharide-induced myocardial contractile dysfunction: Role of autophagy (Retracted article. See vol. 189, pg. 178, 2022)
Cardiac-specific overexpression of catalase attenuates lipopolysaccharide-induced myocardial contractile dysfunction: Role of autophagy (Retracted article. See vol. 189, pg. 178, 2022)
复制标题
过氧化氢酶的心脏特异性过度表达减弱脂多糖诱导的心肌收缩功能障碍：自噬的作用。
DOI：
10.1016/j.freeradbiomed.2012.07.084
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发表时间：
2012-09-15
影响因子：
7.4
通讯作者：
Ren, Jun
中科院分区：
文献类型：
--
作者：
Turdi, Subat;Han, Xuefeng;Ren, Jun
革兰氏阴性菌产生的脂多糖(LPS)是脓毒症的主要诱因，可导致心血管衰竭。越来越多的证据表明，活性氧(ROS)在脓毒症的心血管并发症中起着重要作用。本研究旨在探讨心肌特异的过氧化氢酶过表达在脂多糖诱导的心脏收缩功能障碍中的作用及其机制(S)，重点是自噬。用脂多糖(6 mg/kg)攻击过氧化氢酶转基因小鼠和野生型FVB小鼠，评价心功能。采用荧光显微镜、Western印迹、TUNEL法、半胱氨酸天冬氨酸氨基转移酶-3(caspase-3)活性和羰基形成检测氧化应激、自噬、细胞凋亡和蛋白质损伤水平。用Kaplan-Meier曲线描述脂多糖治疗后的存活率。我们的结果显示，过氧化氢酶小鼠的死亡率低于FVB小鼠。超声心动图和心肌细胞收缩功能显示，注射脂多糖导致心肌收缩能力下降，其作用可被过氧化氢酶过表达所阻断。脂多糖诱导TNE-α水平升高、自噬、细胞凋亡(TUNEL、caspase-3激活、caspase-3裂解)、ROS和O-2(中心点)的产生以及蛋白质羰基的形成，这些作用可被过氧化氢酶过表达显著减弱。电子显微镜显示，在内毒素治疗后，以线粒体损伤为特征的局灶性心肌损伤，在过氧化氢酶小鼠中没有那么严重。有趣的是。抗氧化剂N-乙酰半胱氨酸和自噬抑制剂3-甲基腺嘌呤可预防脂多糖诱导的心肌细胞收缩功能障碍。综上所述，我们的数据显示，过氧化氢酶对脂多糖诱导的心功能障碍和死亡率具有保护作用，这可能与抑制氧化应激和自噬有关。(C)2012 Elsevier Inc.保留所有权利。
Lipopolysaccharide (LPS) from gram-negative bacteria is a major initiator of sepsis, leading to cardiovascular collapse. Accumulating evidence has indicated a role of reactive oxygen species (ROS) in cardiovascular complications in sepsis. This study was designed to examine the effect of cardiac-specific overexpression of catalase in LPS-induced cardiac contractile dysfunction and the underlying mechanism(s) with a focus on autophagy. Catalase transgenic and wild-type FVB mice were challenged with LPS (6 mg/kg) and cardiac function was evaluated. Levels of oxidative stress, autophagy, apoptosis, and protein damage were examined using fluorescence microscopy, Western blot, TUNEL assay, caspase-3 activity, and carbonyl formation. A Kaplan-Meier curve was constructed for survival after LPS treatment. Our results revealed a lower mortality in catalase mice compared with FVB mice after LPS challenge. LPS injection led to depressed cardiac contractile capacity as evidenced by echocardiography and cardiomyocyte contractile function, the effect of which was ablated by catalase overexpression. LPS treatment induced elevated TNE-alpha level, autophagy, apoptosis (TUNEL, caspase-3 activation, cleaved caspase-3), production of ROS and O-2(center dot-), and protein carbonyl formation, the effects of which were significantly attenuated by catalase overexpression. Electron microscopy revealed focal myocardial damage characterized by mitochondrial injury after LPS treatment, which was less severe in catalase mice. Interestingly. LPS-induced cardiomyocyte contractile dysfunction was prevented by the antioxidant N-acetylcysteine and the autophagy inhibitor 3-methyladenine. Taken together, our data revealed that catalase protects against LPS-induced cardiac dysfunction and mortality, which may be associated with inhibition of oxidative stress and autophagy. (c) 2012 Elsevier Inc. All rights reserved.