A humanin analog decreases oxidative stress and preserves mitochondrial integrity in cardiac myoblasts.
A humanin analog decreases oxidative stress and preserves mitochondrial integrity in cardiac myoblasts.
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DOI：
10.1016/j.bbrc.2013.08.055
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发表时间：
2013-10-18
影响因子：
3.1
通讯作者：
Muzumdar, Radhika
中科院分区：
文献类型：
--
作者：
Klein, Laura E.;Cui, Lingguang;Gong, Zhenwei;Su, Kai;Muzumdar, Radhika
内源性肽humanin的有效类似物（HNG）在体内保护心肌缺血-再灌注（MI-R）损伤，减少梗死面积并改善心功能。由于氧化应激有助于从MI-R的损害，我们测试的假设：1。HNG通过激活抗氧化防御机制提供心脏保护，从而保护线粒体结构，2。这种保护需要一对非受体酪氨酸激酶c-Abl和Arg的活性。大鼠心肌成肌细胞（H9 C2细胞）暴露于纳摩尔浓度的HNG和过氧化氢（H2 O2）。在H2 O2存在下用HNG处理的细胞表现出减少的细胞内活性氧（ROS），保留线粒体膜电位、ATP水平和线粒体结构。HNG在5分钟内诱导过氧化氢酶和谷胱甘肽过氧化物酶（GPx）的活化，并在30分钟内降低氧化还原型谷胱甘肽的比例。siRNA敲除Abl和Arg，但都不是单独的，废除了HNG介导的ROS减少暴露于H2 O2的成肌细胞。这些研究结果表明，HNG介导的，Abl和Arg依赖性，快速和持续激活的关键细胞防御系统和衰减的氧化应激，提供机制的见解观察HNG介导的心脏保护在体内。
A potent analog (HNG) of the endogenous peptide humanin protects against myocardial ischemia-reperfusion (MI-R) injury in vivodecreasing infarct size and improving cardiac function. Since oxidative stress contributes to the damage from MI-R we tested the hypotheses that: 1. HNG offers cardioprotection through activation of antioxidant defense mechanisms leading to preservation of mitochondrial structure and that, 2. the activity of either of a pair of non-receptor tyrosine kinases, c-Abl and Arg is required for this protection. Rat cardiac myoblasts (H9C2 cells) were exposed to nanomolar concentrations of HNG and to hydrogen peroxide (H2O2). Cells treated with HNG in the presence of H2O2 demonstrated reduced intracellular reactive oxygen species (ROS), preserved mitochondrial membrane potential, ATP levels and mitochondrial structure. HNG induced activation of catalase and glutathione peroxidase (GPx) within 5 minutes and decreased the ratio of oxidized to reduced glutathione within 30 minutes. siRNA knockdown of both Abl and Arg, but neither alone, abolished the HNG-mediated reduction of ROS in myoblasts exposed to H2O2. These findings demonstrate an HNG-mediated, Abl- and Arg-dependent, rapid and sustained activation of critical cellular defense systems and attenuation of oxidative stress, providing mechanistic insights into the observed HNG-mediated cardioprotection in vivo.
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DOI：
10.1152/ajpheart.00711.2002
发表时间：
2003-02-01
影响因子：
4.8
作者：
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通讯作者：
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影响因子：
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