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

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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.