Role of mitochondrial superoxide dismutase in contraction-induced generation of reactive oxygen species in skeletal muscle extracellular space
Role of mitochondrial superoxide dismutase in contraction-induced generation of reactive oxygen species in skeletal muscle extracellular space
复制标题
DOI：
10.1152/ajpcell.00322.2003
复制
发表时间：
2004-05-01
影响因子：
5.5
通讯作者：
Jackson, MJ
中科院分区：
文献类型：
--
作者：
McArdle, A;van der Meulen, J;Jackson, MJ
骨骼肌的收缩产生细胞外空间中超氧阴离子浓度和羟基自由基活性的增加。这些活性氧的来源尚不清楚。我们测试的假设，一个苛刻的等长收缩协议后，超氧阴离子和羟基自由基的活性在细胞外空间的肌肉的主要来源是线粒体产生的超氧阴离子，并与MnSOD活性的减少，超氧阴离子的浓度在细胞外空间是不变的，但羟基自由基的浓度降低。对于来自成年（6-8月龄）野生型（Sod 2（+/+））小鼠和MnSOD基因杂合的敲除小鼠（Sod 2（+/+））的腓肠肌，通过微透析测量细胞外空间中的超氧阴离子浓度和羟基自由基活性。一个15分钟的协议，180等长收缩诱导细胞色素c的减少，作为超氧阴离子浓度的指标，在细胞外空间的Sod 2（+/+）和Sod 2（+/+）小鼠的快速，同等的增加，而羟基自由基的活性，通过形成2，3-二羟基苯甲酸盐从水杨酸增加，只在细胞外空间的Sod 2（+/+）小鼠的肌肉。收缩方案后，Sod 2（+/+）和Sod 2（+/+）小鼠细胞外空间中超氧阴离子浓度增加没有差异，这支持了超氧阴离子不是直接来自线粒体的假设。相比之下，获得的数据表明，从野生型小鼠肌肉的细胞外空间中的羟基自由基浓度的增加后，收缩协议最有可能的结果从MnSOD活性产生的过氧化氢的降解。
Contractions of skeletal muscles produce increases in concentrations of superoxide anions and activity of hydroxyl radicals in the extracellular space. The sources of these reactive oxygen species are not clear. We tested the hypothesis that, after a demanding isometric contraction protocol, the major source of superoxide and hydroxyl radical activity in the extracellular space of muscles is mitochondrial generation of superoxide anions and that, with a reduction in MnSOD activity, concentration of superoxide anions in the extracellular space is unchanged but concentration of hydroxyl radicals is decreased. For gastrocnemius muscles from adult (6-8 mo old) wild-type (Sod2(+/+)) mice and knockout mice heterozygous for the MnSOD gene (Sod2(+/+)), concentrations of superoxide anions and hydroxyl radical activity were measured in the extracellular space by microdialysis. A 15-min protocol of 180 isometric contractions induced a rapid, equivalent increase in reduction of cytochrome c as an index of superoxide anion concentrations in the extracellular space of Sod2(+/+) and Sod2(+/+) mice, whereas hydroxyl radical activity measured by formation of 2,3-dihydroxybenzoate from salicylate increased only in the extracellular space of muscles of Sod2(+/+) mice. The lack of a difference in increase in superoxide anion concentration in the extracellular space of Sod2(+/+) and Sod2(+/+) mice after the contraction protocol supported the hypothesis that superoxide anions were not directly derived from mitochondria. In contrast, the data obtained suggest that the increase in hydroxyl radical concentration in the extracellular space of muscles from wild-type mice after the contraction protocol most likely results from degradation of hydrogen peroxide generated by MnSOD activity.