Up-regulation of calcium-dependent proteolysis in human myoblasts under acute oxidative stress
Up-regulation of calcium-dependent proteolysis in human myoblasts under acute oxidative stress
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DOI：
10.1016/j.yexcr.2009.07.025
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发表时间：
2010-01-01
影响因子：
3.7
通讯作者：
Poussard, Sylvie
中科院分区：
文献类型：
--
作者：
Dargelos, Elise;Brule, Cedric;Poussard, Sylvie
肌纤维的再生潜力降低，最有可能是由于卫星细胞的数量和/或功能减少，可能在肌肉老化的进展中发挥重要作用。活性氧簇的积累与肌肉减少症明显相关，并可能导致卫星细胞功能受损。在这项工作中，我们研究了过氧化氢在培养的人骨骼肌卫星细胞中产生的氧化应激的影响。我们特别关注钙蛋白酶的活性和调节。已知这些钙依赖性蛋白酶调节许多转导途径，包括凋亡，并在卫星细胞功能中发挥关键作用。在我们的实验条件下，诱导钙浓度增加，蛋白质氧化和凋亡性细胞死亡，钙蛋白酶的表达和活性的显着上调，观察和ATP合成酶，呼吸链的主要组成部分，被确定为钙蛋白酶的目标。有趣的是，我们能够保护细胞免受H2 O2诱导的影响，并通过从松树皮中提取的天然抗氧化剂（Oligopin（R））防止钙蛋白酶上调。这些数据有力地表明，氧化应激可通过钙蛋白酶依赖性途径损害卫星细胞功能，并且抗氧化剂如Oligopin（R）可防止细胞凋亡和钙蛋白酶激活。(C)2009 Elsevier Inc. All rights reserved.
The reduced regenerative potential of muscle fibres, most likely due to a decreased number and/or function of satellite cells, could play a significant role in the progression of muscle ageing. Accumulation of reactive oxygen species has been clearly correlated to sarcopenia and could contribute to the impairment of satellite cell function. In this work we have investigated the effect of oxidative stress generated by hydrogen peroxide in cultured human skeletal muscle satellite cells. We specifically focused on the activity and regulation of calpains. These calcium-dependent proteases are known to regulate many transduction pathways including apoptosis and play a critical role in satellite cell function. In our experimental conditions, which induce an increase in calcium concentration, protein oxidation and apoptotic cell death, a significant up-regulation of calpain expression and activity were observed and ATP synthase, a major component of the respiratory chain, was identified as a calpain target. Interestingly we were able to protect the cells from these H2O2-induced effects and prevent calpain up-regulation with a natural antioxidant extracted from pine bark (Oligopin (R)). These data strongly suggest that oxidative stress could impair satellite cell functionality via calpain-dependent pathways and that an antioxidant such as Oligopin (R) could prevent apoptosis and calpain activation. (C) 2009 Elsevier Inc. All rights reserved.