Shuzo Kumagai

Endurance exercise increases the SIRT1 and peroxisome proliferator-activated receptor γ coactivator-1α protein expressions in rat skeletal muscle

Peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) is considered to play a pivotal role in the exercise-induced metabolic adaptation of skeletal muscle. Although the oxidized form of nicotinamide adenine dinucloetide (NAD(+))-dependent histone deacetylase SIRT1 has been shown to mediate PGC-1alpha-induced metabolic adaptation, the effect of endurance exercise on the SIRT1 protein remains to be elucidated. The purposes of this study were (1) to investigate the distribution of SIRT1 and PGC-1alpha proteins in skeletal muscle and (2) to examine the effects of acute endurance exercise and low- or high-intensity exercise training on SIRT1 and PGC-1alpha protein expressions and on the metabolic components in rat skeletal muscle. Both the SIRT1 and PGC-1alpha proteins preferentially accumulate in red oxidative muscles. Acute endurance exercise on a motor-driven treadmill (20 m/min, 18.5% incline, 45 minutes) increases the PGC-1alpha protein expression at 18 hours after exercise and the SIRT1 protein expression at 2 hours after exercise in the soleus muscle. In the training experiment, the rats were divided into control, low-intensity (20 m/min, 18.5% incline, 90 min/d), and high-intensity (30 m/min, 18.5% incline, 60 min/d) training groups. After 14 days of training, the SIRT1 and PGC-1alpha proteins, hexokinase activity, mitochondrial proteins and enzyme activities, and glucose transporter 4 protein in the soleus muscle were increased by both trainings. In the plantaris muscle, SIRT1, hexokinase activity, mitochondrial proteins and enzyme activities, and glucose transporter 4 were increased by high-intensity training whereas the PGC-1alpha was not. These results suggest that endurance exercise increases the skeletal muscle SIRT1 protein content. In addition, the findings also raise the possibility that the SIRT1 protein expression may play a potentially important role in such adaptations, whereas an increase in the PGC-1alpha protein expression is not necessary for such adaptations.

The effects of moderate-, strenuous- and over-training on oxidative stress markers, DNA repair, and memory, in rat brain

We have tested the hypothesis that training with moderate- (MT), strenuous- (ST), or over- (OT) load can cause alterations in memory, lipid peroxidation, protein oxidation, DNA damage, activity of 8-oxoG-DNA glycosylase (OGG1) and brain-derived neurotrophic factor (BDNF), in rat brain. Rat memory was assessed by a passive avoidance test and the ST and OT group demonstrated improved memory. The content of BDNF was increased only in the OT group. The oxidative damage of lipids and DNA, as measured by thiobarbituric acid reactive substances (TBARS), and 8-hydroxydeoxyguanosine (8-OHdG), did not change significantly with exercise. Similarly, the activity of DNA repair enzyme, 8-oxoguanine DNA glycosylase (OGG1), was not altered with exercise training. On the other hand, the content of reactive carbonyl derivatives (RCDs) decreased in all groups and the decrease reached significance levels in the ST and OT groups. The activity of the proteasome complex increased in the brain of OT. The findings of this study imply that over-training does not induce oxidative stress in the brain and does not cause loss of memory. The improved memory was associated with enhanced BDNF content.

A longitudinal assessment of anaerobic threshold and distance-running performance.

Longitudinal changes in the anaerobic threshold (AT) and distance-running performances (DRP) were assessed with a 4.5-month interval between the pre-, mid-, and post-tests in a relatively homogeneous (in terms of both maximal aerobic power and DRP) sample of 21 male, trained, endurance runners (means age = 18.5 yr) than had been employed previously. ANOVA with repeated measures followed by the Newman- Keuls post-hoc comparison revealed that there were significant alterations in both DRP and AT. Even in this improved state, higher relationships (r greater than or equal to 0.75) between the DRP and AT-related attributes held up consistently over the 9-month training period. Anaerobic threshold (expressed as ml O2 X min-1 X kg-1) showed a correlation higher than 0.80 with 10,000-m race time in every set of tests. When the relationships between the absolute amount of change in the Vo2@AT and the absolute amount of change in DRP were evaluated, significant correlations (r = -0.56 to -0.83) were found in several different time periods. Running velocity at AT (V@AT) also improved significantly, and was closely related to DRP changes. It is speculated that DRP changes are more directly accounted for by the Vo2@AT and/or V@AT changes rather than changes in other physiological attributes.

Effects of exercise on brain function: role of free radicals

Reactive oxygen species (ROS) are continuously generated during aerobic metabolism. Certain levels of ROS, which could be dependent on the type of cell, cell age, history of ROS exposure, etc., could facilitate specific cell functions. Indeed, ROS stimulate a number of stress responses and activate gene expression for a wide range of proteins. It is well known that increased levels of ROS are involved in the aging process and the pathogenesis of a number of neurodegenerative diseases. Because of the enhanced sensitivity of the central nervous system to ROS, it is especially important to maintain the normal redox state in different types of neuro cells. In the last decade it became clear that regular exercise beneficially affects brain function as well, and can play an important preventive and therapeutic role in stroke and in Alzheimers and Parkinsons diseases. The effects of exercise appear to be very complex and could include neurogenesis via neurotrophic factors, increased capillarization, decreased oxidative damage, and increased proteolytic degradation by proteasome and neprilysin. Data from our and other laboratories indicate that exercise-induced modulation of ROS levels plays a role in the protein content and expression of brain-derived neurotrophic factor, tyrosine recepetor kinase B, and cAMP response element binding protein, resulting in better function and increased neurogenesis. The enhanced activities of proteasome and neprilysin result in decreased accumulation of carbonyls and amyloid beta-proteins, as well as improved memory. It appears that exercise-induced modulation of the redox state is an important means by which exercise benefits brain function, increases the resistance against oxidative stress, and facilitates recovery from oxidative stress.

Relationships of anaerobic threshold and onset of blood lactate accumulation with endurance performance

SummaryThis study was undertaken to compare the contribution of both the anaerobic threshold (AT) and onset of blood lactate accumulation (OBLA) with endurance performance in eleven non-endurance trained active male adults. AT determination was based upon both blood lactate and gas exchange criteria, while OBLA was determined as the point corresponding to a blood lactate concentration of 4 mmol·l−1. A dependent t-test revealed significantly higher values for OBLA related variables as compared with corresponding AT related variables, thereby validating the comparison of these two categories of variables in relation to endurance performance. Approximately 67, 60, 37, and 50% of the variance in endurance performance were accounted for by

Decreased serum brain-derived neurotrophic factor in trained men

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Short-term adenosine monophosphate–activated protein kinase activator 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside treatment increases the sirtuin 1 protein expression in skeletal muscle

O2 (ml · kg−1 · min−) AT-WR, OBLS-