Alterations in mitochondrial function, hydrogen peroxide release and oxidative damage in mouse hind-limb skeletal muscle during aging
Alterations in mitochondrial function, hydrogen peroxide release and oxidative damage in mouse hind-limb skeletal muscle during aging
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DOI：
10.1016/j.mad.2005.11.004
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发表时间：
2006-03-01
影响因子：
5.3
通讯作者：
Van Remmen, H
中科院分区：
文献类型：
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作者：
Mansouri, A;Muller, FL;Van Remmen, H
在来自年轻（6-8个月）和老年（27-29个月）野生型和杂合Mn-超氧化物歧化酶（MnSOD）敲除小鼠（Sod 2（+/-））的后肢骨骼肌中测量线粒体功能、过氧化氢产生和氧化损伤。Sod 2（+/-）小鼠中MnSOD活性的降低使这些小鼠成为检查终身升高的内源性线粒体氧化应激对线粒体功能的影响的良好模型。与年轻的野生型小鼠相比，从野生型小鼠分离的骨骼肌线粒体中ATP的产生随着年龄的增长而减少约30%，并且在年轻和老年Sod 2（+/-）小鼠的线粒体中减少40-45%。在野生型和Sod 2（+/-）小鼠中，骨骼肌线粒体释放的过氧化氢随年龄增加40-50%，但在Sod 2（+/-）小鼠的线粒体中并不更高。与野生型小鼠相比，年轻和老年Sod 2（+/-）小鼠中电子传递复合物I和V的活性降低25-30%，并且在来自老年野生型和老年Sod 2（+/-）小鼠的线粒体中降低25-30%。与野生型小鼠相比，DNA氧化损伤（oxo 8dG水平）随年龄增加超过45%，年轻Sod（+/-）小鼠中超过130%。这些数据表明，小鼠骨骼肌中的线粒体氧化应激随着年龄的增长而增加，导致线粒体功能的改变。此外，MnSOD活性降低所产生的氧化应激增加不会加剧衰老过程中的这些变化。(c)2005爱思唯尔爱尔兰有限公司保留所有权利。
Mitochondrial function, hydrogen peroxide generation and oxidative damage were measured in hind-limb skeletal muscle from young (6-8 month) and old (27-29 month) wildtype and heterozygous Mn-superoxide dismutase (MnSOD) knockout mice (Sod2(+/-)). The reduction in MnSOD activity in the Sod2(+/-) mice makes these mice a good model to examine the implications of life-long elevated endogenous mitochondrial oxidative stress on mitochondrial function. ATP production was reduced approximately 30% with age in skeletal muscle mitochondria isolated from wildtype mice, and reduced 40-45% in mitochondria from both young and old Sod2(+/-) mice compared to the young wildtype mice. Release of hydrogen peroxide from skeletal muscle mitochondria increased 40-50% with age in both wildtype and Sod2(+/-) but was not higher ill mitochondria from Sod2(+/-) mice. Activities of electron transport Complexes I and V were decreased 25-30% in both young and old Sod2(+/-) mice compared to wildtype mice, and were 25-30% lower in mitochondria from old wildtype and old Sod2(+/-) mice. DNA oxidative damage (oxo8dG levels) increased more than 45% with age and over 130% in the young Sod(+/-) mice compared to the wildtype mice. These data show that mitochondrial oxidative stress in mouse skeletal muscle is increased with age, leading to alterations in mitochondrial function. In addition, increased oxidative stress generated by reduced activity of MnSOD does not exacerbate these alterations during aging. (c) 2005 Elsevier Ireland Ltd. All rights reserved.