The effect of endurance training on glutathione (GSH) status and antioxidant enzyme system was investigated in skeletal muscle, heart, and liver of female Sprague-Dawley rats pair fed an isocaloric diet. Ten weeks of treadmill training (25 m/min, 10% grade for 2 h/day, 5 days/wk) increased citrate synthase activity in the deep vastus lateralis (DVL) and soleus muscles by 79 and 39%, respectively (P < 0.01), but not in the heart or liver. In DVL, GSH content was increased 33% (P < 0.05) with training, accompanied by a 64% (P < 0.05) increase in glutamate content but no change in cysteine. Trained rats showed a 62 and 27% higher GSH peroxidase (GPX) and superoxide dismutase (SOD) activity, respectively (P < 0.05), in DVL compared with control rats. In contrast, GSH content and glutathione reductase (GR) activity in soleus declined with training (P < 0.05), whereas activities of GPX and SOD remained unchanged. Training did not alter GSH status in the liver or plasma but significantly decreased the GSH-to glutathione disulfide ratio in the heart. In addition, GR activity in the liver and GSH sulfur-transferase activity in the heart and DVL were significantly lower in the trained vs control rats DVL muscle had threefold higher gamma-glutamyl transpeptidase activity compared with other tissues; however no significant alteration was observed in the activity of gamma-glutamyltranspeptidase or gamma-glutamylcysteine synthetase in the liver, heart, or skeletal muscle. These data indicate that endurance training can cause tissue- and muscle fiber-specific adaptation of antioxidant systems and that GSH homeostasis in extrahepatic tissues may be determined by utilization and uptake of GSH via the gamma-glutamyl cycle.

The goal of this experiment was to examine contraction-mediated activation of superoxide dismutase (SOD) gene expression in rat superficial vastus lateralis (SVL, type IIb) and deep vastus lateralis (DVL, type IIa) muscles. Female Sprague-Dawley rats were randomly divided into exercise (E) and control (C) groups that were sacrificed at 0, 1, 2, 4, 10, 24, and 48 h (n=6) following an acute bout of treadmill exercise (25 m/min, 5% grade) to exhaustion (running time approximately equals 1 h). Nuclear factor-kappaB (NF-kappaB) in DVL and SVL showed maximal binding at 2 and 10 h respectively, and remained elevated. Activator protein-1 (AP-1) showed maximal binding at 1 h post-exercise, and returned to resting levels at 10 h in both muscles. Mn SOD mRNA abundance in the DVL was increased at 0 (P<0.01), 1, and 2 h (P<0.05) post-exercise, whereas Mn SOD protein was unchanged. In SVL, Mn SOD mRNA abundance was not altered by exercise, whereas Mn SOD protein content was increased at 10 (P<0.05) and 24 h (P<0.075) post-exercise. CuZn SOD mRNA was unchanged with exercise in DVL and SVL, but CuZn SOD protein was elevated 48 h after exercise in both DVL and SVL (P<0.01). Activities of Mn SOD, CuZn SOD and total SOD showed no change with exercise in either muscle examined. These findings indicate that an acute bout of exercise can increase binding of NF-kappaB and AP-1 in both SVL and DVL, which may stimulate Mn SOD mRNA transcription in the more oxidative type DVL muscle. The increased CuZn SOD protein contents seen post-exercise, without increases in mRNA abundance in both DVL and SVL, suggest a translational mechanism in this SOD isoform.

Strenuous exercise is characterized by an increased oxygen consumption and disturbance of intracellular prooxidant-antioxidant homeostasis. At least three biochemical pathways, that is, mitochondrial electron transport chain, xanthine oxidase, and polymorphoneutrophil have been identified as potential sources of intracellular free radical generation during exercise. These deleterious reactive oxygen species pose a serious threat to the cellular antioxidant defense system, such as diminished reserve of antioxidant vitamins and glutathione, and have been shown to cause oxidative damage in exercising and/or exercised muscle and other tissues. However, enzymatic and nonenzymatic antioxidants have demonstrated great versatility and adaptability in response to acute and chronic exercise. The delicate balance between prooxidants and antioxidants during exercise may be altered with aging. Study of the complicated interaction between aging and exercise under the influence of reactive oxygen species would provide more definitive information as to how much aged individuals should be involved in physical activity and whether supplementation of nutritional antioxidants would be desirable.

The effects of endurance training on the enzyme activity, protein content, and mRNA abundance of Mn and CuZn superoxide dismutase (SOD) were studied in various phenotypes of rat skeletal muscle. Female Sprague-Dawley rats were randomly divided into trained (T, n = 8) and untrained (U, n = 8) groups. Training, consisting of treadmill running at 27 m/min and 12% grade for 2 h/day, 5 days/wk for 10 wk, significantly increased citrate synthase activity ( P < 0.01) in the type I (soleus), type IIa (deep vastus lateralis, DVL), and mixed type II (plantaris) muscles but not in type IIb (superficial vastus lateralis, SVL) muscle. Mitochondrial (Mn) SOD activity was elevated by 80% ( P < 0.05) with training in DVL. SVL and plantaris muscle in T rats showed 54 and 42% higher pooled immunoreactive Mn SOD protein content, respectively, than those in U rats. However, no change in Mn SOD mRNA level was found in any of the muscles. CuZn SOD activity, protein content, and mRNA level in general were not affected by training, except for a 160% increase in pooled CuZn SOD protein in SVL. Training also significantly increased glutathione peroxidase and catalase activities ( P < 0.05), but only in DVL muscle. These data indicate that training adaptations of Mn SOD and other antioxidant enzymes occur primarily in type IIa fibers, probably as a result of enhanced free radical generation and modest antioxidant capacity. Differential training responses of mRNA, enzyme protein, and activity suggest that separate cellular signals may control pre- and posttranslational regulation of SOD.