Hindlimb unloading increases oxidative stress and disrupts antioxidant capacity in skeletal muscle
Hindlimb unloading increases oxidative stress and disrupts antioxidant capacity in skeletal muscle
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DOI：
10.1016/s0891-5849(03)00186-2
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发表时间：
2003-07-01
影响因子：
7.4
通讯作者：
Demaree, SR
中科院分区：
文献类型：
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作者：
Lawler, JM;Song, W;Demaree, SR
太空飞行和地面模型（例如，后肢卸载）导致显著的骨骼肌萎缩和虚弱。导致肌肉萎缩的病理状况（即，心力衰竭、肌营养不良、败血症、COPD、癌症）的特征在于升高的“氧化应激”，其中抗氧化剂防御被氧化剂产生压倒。然而，在骨骼肌后肢卸荷的存在，细胞机制和氧化应激的后果知之甚少。因此，我们检查了后肢卸载对后肢肌肉抗氧化酶（例如，超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶）、非酶抗氧化剂清除能力（ASC）、总氢过氧化物和二氯氢荧光素二乙酸酯（DCFH-DA）氧化（氧化应激的直接指标）。12只6月龄Sprague道利大鼠随机分为后肢去负荷28 d组（n = 6）和对照组（n = 6）。后肢去负荷导致比目鱼肌中锰超氧化物歧化酶活性小幅下降（10.1%），而铜锌超氧化物歧化酶活性增加71.2%。与此相反，过氧化氢酶和谷胱甘肽过氧化物酶，抗氧化酶，去除氢过氧化物，显着减少比目鱼与后肢卸载54.5%和16.1%，分别。后肢去负荷也显著降低ASC。后肢去负荷使比目鱼肌脂质过氧化氢水平增加21.6%，后肢肌DCFH-DA氧化增加162.1%。这些结果表明，后肢卸载导致抗氧化状态的破坏，氢过氧化物的升高和氧化应激的增加。(C)2003年爱思唯尔公司
Skeletal muscle disuse with space-flight and ground-based models (e.g., hindlimb unloading) results in dramatic skeletal muscle atrophy and weakness. Pathological conditions that cause muscle wasting (i.e., heart failure, muscular dystrophy, sepsis, COPD, cancer) are characterized by elevated "oxidative stress," where antioxidant defenses are overwhelmed by oxidant production. However, the existence, cellular mechanisms, and ramifications of oxidative stress in skeletal muscle subjected to hindlimb unloading are poorly understood. Thus we examined the effects of hindlimb unloading on hindlimb muscle antioxidant enzymes (e.g., superoxide dismutase, catalase, glutathione peroxidase), nonenzymatic antioxidant scavenging capacity (ASC), total hydroperoxides, and dichlorohydrofluorescein diacetate (DCFH-DA) oxidation, a direct indicator of oxidative stress. Twelve 6 month old Sprague Dawley rats were divided into two groups: 28 d of hindlimb unloading (n = 6) and controls (n = 6). Hindlimb,unloading resulted in a small decrease in Mn-superoxide dismutase activity (10.1%) in the soleus muscle, while Cu,Zn-superoxide dismutase increased 71.2%. In contrast, catalase and glutathione peroxidase, antioxidant enzymes that remove hydroperoxides, were significantly reduced in the soleus with hindlimb unloading by 54.5 and 16.1%, respectively. Hindlimb unloading also significantly reduced ASC. Hindlimb unloading increased soleus lipid hydroperoxide levels by 21.6% and hindlimb muscle DCFH-DA oxidation by 162.1%. These results indicate that hindlimb unloading results in a disruption of antioxidant status, elevation of hydroperoxides, and an increase in oxidative stress. (C) 2003 Elsevier Inc.