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

运动会增加活性氧的产生，这可能会伤害细胞，而它通常被推荐为一种促进健康的生活方式。关于运动对蛋白质氧化应激影响的报道有限。本文研究了中等强度的规律性运动对中青年大鼠认知功能和脑内蛋白质氧化修饰的影响。每周游泳5天，持续9周后，对动物进行被动和主动回避测试。然后，我们测量了蛋白质羰基和其他氧化应激标志物的脂质和DNA以及蛋白酶体活性在大脑中。运动期后，中年大鼠表现出轻微但显着的改善被动回避活动。青年和中年动物都表现出显着的激活主动回避活动的运动。与这些观察结果平行，蛋白质羰基，氧化应激的标志物，在大脑中减少。蛋白质印迹分析表明，神经丝和微管蛋白可能是主要的羰基化蛋白质。应该强调的是，硫代丁酸反应物质，脂质过氧化物的制造商，和8-羟基鸟苷，DNA氧化的标志物，似乎没有改变的运动，这表明，减少蛋白质氧化是唯一相关的功能，大脑在氧化应激。有趣的是，大脑的蛋白酶体活性被运动上调。可以想象，蛋白酶体降解氧化修饰的蛋白质，从而减少大脑中潜在的有害分子。本研究的结果可能提供一个证据，迄今为止还没有认识到适度的定期运动的有益效果。

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.