Effect of lifelong overexpression of HSP70 in skeletal muscle on age-related oxidative stress and adaptation after nondamaging contractile activity
Effect of lifelong overexpression of HSP70 in skeletal muscle on age-related oxidative stress and adaptation after nondamaging contractile activity
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DOI：
10.1096/fj.05-4935fje
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发表时间：
2006-07-01
期刊：
影响因子：
4.8
通讯作者：
McArdle, Anne
中科院分区：
文献类型：
--
作者：
Broome, Caroline S.;Kayani, Anna C.;McArdle, Anne
骨骼肌老化的特点是萎缩、特定力量产生不足、对损伤的敏感性增加以及严重损伤后恢复不完全。年老小鼠的肌肉产生热休克蛋白（HSP）以应对压力的能力严重减弱。我们实验室使用 HSP70 过度表达小鼠进行的研究表明，骨骼肌中 HSP70 的终生过度表达可以提供针对损伤的保护，并促进老年小鼠肌肉损伤后的成功恢复。 HSP70 提供这种保护的机制尚不清楚。衰老与氧化产物的积累有关，有人提出这可能在与年龄相关的肌肉功能障碍中发挥重要作用。与成年 WT 小鼠相比，老年野生型 (WT) 小鼠的肌肉表现出脂质过氧化增加、谷胱甘肽含量减少、过氧化氢酶和超氧化物歧化酶 (SOD) 活性增加，并且在收缩后无法激活核因子 (NF)-κ B。相比之下，老HSP70过表达小鼠肌肉中的脂质过氧化水平、谷胱甘肽含量以及过氧化氢酶和SOD活性与成年小鼠相似，并且这些肌肉在收缩后也保持激活NF-κB的能力。这些数据为老 HSP70 过表达小鼠的肌肉功能保留提供了解释。
Skeletal muscle aging is characterized by atrophy, a deficit in specific force generation, increased susceptibility to injury, and incomplete recovery after severe injury. The ability of muscles of old mice to produce heat shock proteins (HSPs) in response to stress is severely diminished. Studies in our laboratory using HSP70 overexpressor mice demonstrated that lifelong overexpression of HSP70 in skeletal muscle provided protection against damage and facilitated successful recovery after damage in muscles of old mice. The mechanisms by which HSP70 provides this protection are unclear. Aging is associated with the accumulation of oxidation products, and it has been proposed that this may play a major role in age-related muscle dysfunction. Muscles of old wild-type (WT) mice demonstrated increased lipid peroxidation, decreased glutathione content, increased catalase and superoxide dismutase (SOD) activities, and an inability to activate nuclear factor (NF)-kappa B after contractions in comparison with adult WT mice. In contrast, levels of lipid peroxidation, glutathione content, and the activities of catalase and SOD in muscles of old HSP70 overexpressor mice were similar to adult mice and these muscles also maintained the ability to activate NF-kappa B after contractions. These data provide an explanation for the preservation of muscle function in old HSP70 overexpressor mice.