Release of superoxide from skeletal muscle of adult and old mice: an experimental test of the reductive hotspot hypothesis
Release of superoxide from skeletal muscle of adult and old mice: an experimental test of the reductive hotspot hypothesis
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DOI：
10.1111/j.1474-9726.2007.00277.x
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发表时间：
2007-04-01
期刊：
影响因子：
7.8
通讯作者：
Jackson, Malcolm J.
中科院分区：
文献类型：
--
作者：
Close, Graeme L.;Kayani, Anna C.;Jackson, Malcolm J.
增加细胞外产生的活性氧（ROS），作为增加依赖糖酵解代谢的结果，由老的富含维生素A的组织已被声称有助于在老化过程中的氧化损伤的传播（还原热点假说），但该过程还没有在老年动物实验研究。在休息和一段时间的要求等长收缩后，在成年和老年小鼠腓肠肌细胞外液中的超氧化物活性和血液和肝脏中的氧化标记物进行了检查。肌肉微透析液中的超氧化物的活性在休息时成年和老年小鼠之间没有差异，但是在收缩活动期间，来自成年肌肉的微透析液中的超氧化物活性显著增加，但是来自老年肌肉的微透析液中的超氧化物活性没有增加。在休息时，老年小鼠的肝脏中含有增加的丙二醛含量和减少的蛋白质巯基含量与成年小鼠相比，但以下的收缩协议，只有成年小鼠的血清和肝脏中的丙二醛含量显着的，短暂的增加和肝脏中的谷胱甘肽和蛋白质巯基含量的减少。进一步的研究表明，老年小鼠收缩肌肉中缺乏超氧化物释放并不是因为这些肌肉产生的力量减少。这些数据没有提供任何证据表明，增加细胞外超氧化物在休息或收缩骨骼肌的老年小鼠，或从肌肉释放的超氧化物有助于氧化的血液成分在老年小鼠的肝脏中的还原热点假说预测。
Increased extracellular generation of reactive oxygen species (ROS) as a result of increasing reliance on glycolytic metabolism by old mitochondria-rich tissues has been claimed to contribute to the propagation of oxidative damage during aging (the reductive hotspot hypothesis), but the process has not been examined experimentally in old animals. Superoxide activity in the extracellular fluid of gastrocnemius muscle and markers of oxidation in blood and the liver were examined in adult and old mice at rest and following a period of demanding isometric contractions. The activity of superoxide in muscle microdialysates did not differ between adult and old mice at rest, but during contractile activity, there was a significant increase in the superoxide activity in microdialysates from adult muscle but no increase in microdialysates from old muscle. At rest, the liver of old mice contained an increased malonaldehyde content and a decreased protein thiol content in comparison with adult mice, but following the contraction protocol, only the adult mice showed significant, transient increases in the serum and liver malonaldehyde content and a decrease in liver glutathione and protein thiol content. Further studies revealed that the lack of superoxide release from contracting muscle of old mice was not due to reduced force generation by these muscles. These data provide no evidence for an increased extracellular superoxide in resting or contracting skeletal muscle of old mice, or that release of superoxide from muscle contributes to oxidation of blood components in the liver in old mice as is predicted from the reductive hotspot hypothesis.