Exercise protects against doxorubicin-induced markers of autophagy signaling in skeletal muscle
Exercise protects against doxorubicin-induced markers of autophagy signaling in skeletal muscle
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DOI：
10.1152/japplphysiol.00429.2011
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发表时间：
2011-10-01
影响因子：
3.3
通讯作者：
Powers, Scott K.
中科院分区：
文献类型：
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作者：
Smuder, Ashley J.;Kavazis, Andreas N.;Powers, Scott K.
斯穆德AJ，卡瓦齐斯安，Min K，Power SK。运动对阿霉素诱导的骨骼肌自噬信号标志物具有保护作用。应用生理学杂志111：1190-1198,2011。首次发表于2011年7月21日；阿霉素(doi:10.1152/japplphysiol.00429.2011.-Doxorubicin)是一种用于癌症治疗的有效抗肿瘤药物。不幸的是，DOX对骨骼肌也是有毒的，会导致严重的肌肉萎缩。多柔比星对骨骼肌纤维产生毒性的细胞机制(S)尚不清楚。尽管如此，DOX诱导的毒性与活性氧物种的生成增加、氧化损伤以及肌肉纤维内钙蛋白酶和caspase-3蛋白水解酶系统的激活有关。目前尚不清楚DOX治疗后骨骼肌中是否激活了自噬，这是一种可由氧化应激触发的蛋白质分解系统。因此，我们验证了这样的假设，即全身注射DOX会导致大鼠比目鱼肌中自噬标志物的表达增加。我们的结果表明，DOX给药导致肌肉中几个重要的自噬蛋白的mRNA水平和/或蛋白丰度增加，包括：Beclin-1、Atg12、ATG7、LC3、LC3II/LCI比率和组织蛋白L。此外，考虑到耐力运动提高骨骼肌抗氧化能力并保护肌肉免受DOX诱导的氧化应激，我们进行了额外的实验，以确定给药前的运动训练是否会减弱DOX诱导的自噬基因表达的增加。我们的结果清楚地表明，运动可以保护骨骼肌免受DOX诱导的自噬基因的表达。综上所述，我们的研究结果表明，DOX给药增加了骨骼肌中自噬基因的表达，运动可以保护骨骼肌免受DOX诱导的自噬激活。
Smuder AJ, Kavazis AN, Min K, Powers SK. Exercise protects against doxorubicin-induced markers of autophagy signaling in skeletal muscle. J Appl Physiol 111: 1190-1198, 2011. First published July 21, 2011; doi:10.1152/japplphysiol.00429.2011.-Doxorubicin (DOX) is an effective antitumor agent used in cancer treatment. Unfortunately, DOX is also toxic to skeletal muscle and can result in significant muscle wasting. The cellular mechanism(s) by which DOX induces toxicity in skeletal muscle fibers remains unclear. Nonetheless, DOX-induced toxicity is associated with increased generation of reactive oxygen species, oxidative damage, and activation of the calpain and caspase-3 proteolytic systems within muscle fibers. It is currently unknown if autophagy, a proteolytic system that can be triggered by oxidative stress, is activated in skeletal muscles following DOX treatment. Therefore, we tested the hypothesis that systemic administration of DOX leads to increased expression of autophagy markers in the rat soleus muscle. Our results reveal that DOX administration results in increased muscle mRNA levels and/or protein abundance of several important autophagy proteins, including: Beclin-1, Atg12, Atg7, LC3, LC3II-to-LCI ratio, and cathepsin L. Furthermore, given that endurance exercise increases skeletal muscle antioxidant capacity and protects muscle against DOX-induced oxidative stress, we performed additional experiments to determine whether exercise training before DOX administration would attenuate DOX-induced increases in expression of autophagy genes. Our results clearly show that exercise can protect skeletal muscle from DOX-induced expression of autophagy genes. Collectively, our findings indicate that DOX administration increases the expression of autophagy genes in skeletal muscle, and that exercise can protect skeletal muscle against DOX-induced activation of autophagy.