Roles of oxidatively modified proteins in the brain of aging animals : Intervention by moderate regular exercise

运动可以增加活性氧的产生，而活性氧可能会损害细胞，而运动通常被推荐为一种促进健康的生活方式。关于运动对氧化应激对蛋白质影响的报道是有限的。我们研究了适度的定期运动对中青年大鼠认知和大脑中蛋白质氧化修饰的影响。每周游泳5天，连续9周进行被动和主动回避试验。然后，我们测量了蛋白质碳酶和其他脂质和DNA氧化应激的标志物，以及大脑中的蛋白酶体活性。运动期结束后，中年大鼠的被动回避活动有轻微但显著的改善。年轻动物和中年动物都表现出明显的主动回避活动。与这些观察结果同时，氧化应激的标志蛋白羰基在大脑中减少。Western blot分析显示，神经丝和微管蛋白可能是主要的羰基化蛋白。应该强调的是，硫代丁酸反应物质（脂质过氧化的制造者）和8-羟基鸟苷（DNA氧化的标记物）似乎没有因运动而改变，这表明蛋白质氧化的减少与氧化应激方面的大脑功能有独特的关系。有趣的是，大脑的蛋白酶体活动因运动而上调。可以想象，蛋白酶体可以降解氧化修饰的蛋白质，从而减少大脑中潜在的有害分子。目前的研究结果可能会为适度规律运动的有益作用提供一块迄今为止尚未被认识到的证据。

Exercise increases generation of reactive oxygen species that may harm cells while it is often recommended as a health promoting life-style. Reports on the effects of oxidative stress on proteins by exercise is limited. We have investigated that effects of moderate regular exercise on cognition and oxidative modification of proteins in the brain of young and middle-aged rats. The animals were evaluated for passive and active avoidance tests after swimming of 5 days a week for 9 weeks. We then measured protein carbonlys and other markers of oxidative stress for lipid and DNA as well as proteasome activity in the brain.After exercise period, the middle-aged rats exhibited slight but significant improvement of passive avoidance activity. Both young and middle-aged animals showed remarkable activation of active avoidance activity by the exercise. In parallel with these observation, protein carbonyl, a marker of oxidative stress, decreased in the brain. Western blot analysis showed that neurofilaments and tubulins are likely major carbonylated proteins. It should be stressed that thiobarbutyric acid reactive substance, a maker of lipid peroxide, and 8-hyroxyguanosine, a marker of DNA oxidation, did not appear to change by the exercise, suggesting that reduction of protein oxidation is uniquely related to the function of the brain in terms of oxidative stress. Interestingly, proteasome activity of the brain was upregulated by the exercise. It is conceivable that the proteasome degraded oxidatively modified proteins thereby reducing potentially harmful molecules in the brain.The result of the present investigation may provide a piece of evidence so far not recognized for the beneficial effect of moderate regular exercise.