Antioxidant Enzymes In Skeletal Muscle Research Articles

P62/SQSTM1 is required for exercise training‐mediated regulation of antioxidant enzymes in skeletal muscle

Oxidative stress has been implicated in the pathogenesis of skeletal muscle wasting. Regular exercise training prevents oxidative stress‐induced muscle wasting at least partially by improving the antioxidant defense system. It has been shown that p62/sequestosome1 (SQSTM1) competitively binds to Keap1 activating the nuclear factor erythroid 2‐related factor 2 (Nrf2), which stimulates transcription of antioxidant enzymes. However, it remains to be determined if this process is active in skeletal muscle. Therefore, this study aims to determine whether p62 is required for the exercise training‐mediated increase in antioxidant enzymes in skeletal muscle. To do so, we used 3 complementary studies: i) C2C12 myotubes were subjected to 110% cyclic uniaxial stretch for 1 and 6 hours at a frequency of 1 Hz to assess whether stretching regulates p62 mRNA expression; ii) C57BL/6 mice were assigned to either voluntary wheel running for 4 weeks or no exercise to examine whether exercise training regulates p62 protein expression and phosphorylation (Ser351), both of which increase p62 affinity for Keap1 binding; and iii) muscle‐specific p62 knockout (p62MKO) and wild‐type littermates (WT) mice were assigned to either exercise training or sedentary groups, and the muscle content of antioxidant enzymes was determined after 4 weeks of exercise training. Our results demonstrated that p62 mRNA levels were significantly increased at 6 hours of mechanical stretch in C2C12 myotubes. Voluntary running in C57BL/6 mice increased p62 protein and p62 phosphorylation in soleus muscle. Moreover, expression of the Nrf2 target antioxidant gene NQO1 in p62MKO skeletal muscle was abolished compared to WT mice. Loss of p62 in skeletal muscle also blunted the exercise training‐mediated increase in antioxidant enzymes (i.e. Cu/ZnSOD, EcSOD) in soleus muscle. These findings indicate that p62 is required for exercise training‐mediated increase of antioxidant enzymes in skeletal muscle likely via modulation of Nrf2 function.Support or Funding InformationThis study was funded by Grant‐in‐Aid for Challenging Exploratory Research (16K13019) and Grant‐in‐Aid for Scientific Research (B) (15H03080) to M. Okutsu.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

The role of Nrf2 in exercise training‐mediated regulation of antioxidant enzymes in skeletal muscle

Oxidative stress has been implicated in the pathogenesis of skeletal muscle wasting. Regular exercise training prevents oxidative stress‐induced muscle wasting by at least partially improving the antioxidant defense system. However, the underlying molecular mechanisms involved remain elusive. In this study, we assessed whether the nuclear factor erythroid 2‐related factor (Nrf2), the master regulator of antioxidant gene transcription, is essential for the exercise training‐mediated increase in expression of antioxidant enzymes. We performed 3 complementary studies. First, C2C12 myotubes were subjected to 110% cyclic uniaxial stretch for 1 and 6 hours at a frequency of 1 Hz to assess whether stretching regulates mRNA expression of Nrf2. Second, C57BL/6 mice were subjected to either voluntary wheel running for 4 weeks or no exercise to examine whether exercise training regulates Nrf2 and antioxidant enzyme protein expression in muscle. Third, muscle‐specific Nrf2 knockout (Nrf2MKO) and wild‐type littermates (WT) mice were assigned to either exercise training or sedentary groups, and the muscle content of antioxidant enzymes was determined after 4 weeks of exercise training. Our results revealed a significant elevation in Nrf2 mRNA expression in C2C12 myotubes at 6 hours of mechanical stretch. Voluntary running in C57BL/6 mice increased antioxidant enzyme protein (i.e., Cu/ZnSOD, EcSOD) in soleus muscle. Moreover, expression of the Nrf2 target antioxidant gene NQO1 in Nrf2MKO skeletal muscle was abolished compared to WT mice. Loss of Nrf2 in skeletal muscle also blunted the exercise training‐mediated increase in antioxidant enzymes in soleus muscles. These findings indicate that Nrf2 is required for exercise training‐mediated increase of antioxidant enzymes in skeletal muscle.Support or Funding InformationThis study was funded by Grant‐in‐Aid for Challenging Exploratory Research (16K13019) and Grant‐in‐Aid for Scientific Research (B) (15H03080) to M. Okutsu.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Roles of sedentary aging and lifelong physical activity in exchange of glutathione across exercising human skeletal muscle

Reactive oxygen species (ROS) are important signaling molecules with regulatory functions, and in young and adult organisms, the formation of ROS is increased during skeletal muscle contractions. However, ROS can be deleterious to cells when not sufficiently counterbalanced by the antioxidant system. Aging is associated with accumulation of oxidative damage to lipids, DNA, and proteins. Given the pro-oxidant effect of skeletal muscle contractions, this effect of age could be a result of excessive ROS formation. We evaluated the effect of acute exercise on changes in blood redox state across the leg of young (23±1 years) and older (66±2 years) sedentary humans by measuring the whole blood concentration of the reduced (GSH) and oxidized (GSSG) forms of the antioxidant glutathione. To assess the role of physical activity, lifelong physically active older subjects (62±2 years) were included. Exercise increased the venous concentration of GSSG in an intensity-dependent manner in young sedentary subjects, suggesting an exercise-induced increase in ROS formation. In contrast, venous GSSG levels remained unaltered during exercise in the older sedentary and active groups despite a higher skeletal muscle expression of the superoxide-generating enzyme NADPH oxidase. Arterial concentration of GSH and expression of antioxidant enzymes in skeletal muscle of older active subjects were increased. The potential impairment in exercise-induced ROS formation may be an important mechanism underlying skeletal muscle and vascular dysfunction with sedentary aging. Lifelong physical activity upregulates antioxidant systems, which may be one of the mechanisms underlying the lack of exercise-induced increase in GSSG.

Effect of ischemia post-conditioning on skeletal muscle oxidative injury, mTOR, Bax, Bcl-2 proteins expression, and HIF-1α/β-actin mRNA, IL-6/β-actin mRNA and caveolin-3/β-actin mRNA expression in ischemia–reperfusion rabbits

This study is designed to investigate the effect of ischemia post-conditioning on IR-induced skeletal muscle injury in limbs of experimental rabbits. Rabbits are randomized to one of the following three groups: sham control, ischemic reperfusion, ischemic postconditioning. The lipid peroxidation level, antioxidant enzymes activities, skeletal muscle mammalian target of rapamycin (mTOR), Bax, Bcl-2 proteins expression and Bcl-2/Bax, and HIF-1α/β-actin mRNA, interleukin-6 (IL-6)/β-actin mRNA and caveolin-3/β-actin mRNA expression were tested in the current study. The results suggested that ischemic postconditioning might decrease lipid peroxidation level, lactic dehydrogenase (LDH), creatine kinase (CK) activities, Bcl-2 proteins expression and Bcl-2/Bax, HIF-1α/β-actin mRNA expression and increase skeletal muscle antioxidant enzymes activities, Bax protein expression and IL-6/β-actin mRNA and caveolin-3/β-actin mRNA expression. These indicated that protective effect of ischemic postconditioning against IR-induced skeletal muscle injury involve into a complex molecular mechanism. Our research results may offer a theoretical guidance for therapy of related clinical diseases.

Erratum to: Short-term creatine supplementation decreases reactive oxygen species content with no changes in expression and activity of antioxidant enzymes in skeletal muscle

Erratum to: Short-term creatine supplementation decreases reactive oxygen species content with no changes in expression and activity of antioxidant enzymes in skeletal muscle

Mitochondrial ROS and muscle glucose uptake during exercise in transgenic mice

much research has examined the factors regulating skeletal muscle glucose uptake during exercise. Part of the impetus for this work has been to describe and understand the effects of regular physical activity (i.e., exercise training) on muscle glucose uptake and energy substrate partitioning,

Short-term creatine supplementation decreases reactive oxygen species content with no changes in expression and activity of antioxidant enzymes in skeletal muscle

The effect of short-term creatine (Cr) supplementation upon content of skeletal muscle-derived-reactive oxygen species (ROS) was investigated. Wistar rats were supplemented with Cr (5g/kg BW) or vehicle, by gavage, for 6days. Soleus and extensor digitorum longus (EDL) muscles were removed and incubated for evaluation of ROS content using Amplex-UltraRed reagent. The analysis of expression and activity of antioxidant enzymes (superoxide dismutase 1 and 2, catalase and glutathione peroxidase) were performed. Direct scavenger action of Cr on superoxide radical and hydrogen peroxide was also investigated. Short-term Cr supplementation attenuated ROS content in both soleus and EDL muscles (by 41 and 33.7%, respectively). Cr supplementation did not change expression and activity of antioxidant enzymes. Basal TBARS content was not altered by Cr supplementation. In cell-free experiments, Cr showed a scavenger effect on superoxide radical in concentrations of 20 and 40mM, but not on hydrogen peroxide. These results indicate that Cr supplementation decreases ROS content in skeletal muscle possibly due to a direct action of Cr molecule on superoxide radical.

Resveratrol improves insulin resistance of catch-up growth by increasing mitochondrial complexes and antioxidant function in skeletal muscle

Caloric restriction followed by refeeding, a phenomenon known as catch-up growth (CUG), affects mitochondrial function and results in systemic insulin resistance (IR). We investigated the potential of resveratrol (RES) in CUG to prevent IR by increasing activity of the mitochondrial respiratory chain and antioxidant enzymes in skeletal muscle. Rats (8 weeks of age) were divided into 3 groups: normal chow, CUG, and CUG with RES intervention. Skeletal muscle and systemic IR were measured in each group after 4 and 8 weeks. Mitochondrial biogenesis and function, oxidative stress levels, and antioxidant enzyme activity in skeletal muscle were assessed. Catch-up growth–induced IR resulted in significant reductions in both average glucose infusion rate60-120 at euglycemia and skeletal muscle glucose uptake. Mitochondrial citrate synthase activity was lower; and the activity of complexes I to IV in the intermyofibrillar and subsarcolemmal (SS) mitochondria were reduced by 20% to 40%, with the decrease being more pronounced in the SS fraction. Reactive oxygen species levels were significantly higher in intermyofibrillar and SS mitochondria, whereas activities of antioxidant enzymes were decreased. Oral administration of RES, however, increased silent information regulator 1 activity and improved mitochondrial number and insulin sensitivity. Resveratrol treatment decreased levels of reactive oxygen species and restored activities of antioxidant enzymes. This study demonstrates that RES protects insulin sensitivity of skeletal muscle by improving activities of mitochondrial complexes and antioxidant defense status in CUG rats. Thus, RES has therapeutic potential for preventing CUG-related metabolic disorders.

Expression of MnSOD, CuZnSOD and catalase in response to chronic environmental hyperthermia in pigs

Chronic environmental hyperthermia (CEH) has a profound negative effect on mammalian health and performance. The study objective was to determine the extent to which CEH alters antioxidant enzyme expression and free radical production in muscle. We hypothesized that CEH would increase expression of MnSOD, CuZnSOD, and catalase independent of decreased caloric intake. Crossbred gilts (35±4 kg BW; n=6/group) were housed in thermoneutral (TN; 20°C) or heat stress (35°C) conditions for 1 d (HS1), 3 d (HS3), or 7 d (HS7). We also included a TN group that was pair-fed to the HS7 group (TNPF). Pigs were sacrificed following 1, 3, or 7 days of controlled environmental exposure and the red (R) and white (W) semitendinosus (ST) removed. MnSOD gene expression increased 45 and 40% in R and W ST, respectively, and catalase increased 2.3 fold in RST in the HS1 compared to TN. In contrast, antioxidant expression in HS3 and HS7 was similar to or lower than TN in both muscle types. Protein expression mirrored gene expression data, though tended to lag one time point behind. This compensatory failure is due, at least in part, to the reduced caloric intake associated with CEH as the TNPF group had similar or lower expression of CuZnSOD and MnSOD compared to the TN and HS7 groups. These data indicate that CEH alters the expression and abundance of skeletal muscle antioxidant enzymes and that nutritional status may have a significant impact on this effect.

Antioxidant enzymes in skeletal muscle and their modulation by alcohol and the dehydrogenase inhibitors 4-methylpyrazole and cyanamide

Antioxidant enzymes in skeletal muscle and their modulation by alcohol and the dehydrogenase inhibitors 4-methylpyrazole and cyanamide

Exercise training reverses downregulation of HSP70 and antioxidant enzymes in porcine skeletal muscle after chronic coronary artery occlusion

Oxidative stress is associated with muscle fatigue and weakness in skeletal muscle of ischemic heart disease patients. Recently, it was found that endurance training elevates protective heat shock proteins (HSPs) and antioxidant enzymes in skeletal muscle in healthy subjects and antioxidant enzymes in heart failure patients. However, it is unknown whether coronary ischemia and mild infarct without heart failure contributes to impairment of stress proteins and whether exercise training reverses those effects. We tested the hypothesis that exercise training would reverse alterations in muscle TNF-alpha, oxidative stress, HSP70, SOD (Mn-SOD, Cu,Zn-SOD), glutathione peroxidase (GPX), and catalase (CAT) due to chronic coronary occlusion of the left circumflex (CCO). Yucatan swine were divided into three groups (n = 6 each): sedentary with CCO (SCO); 12 wk of treadmill exercise training following CCO (ECO); and sham surgery controls (sham). Forelimb muscle mass-to-body mass ratio decreased by 27% with SCO but recovered with ECO. Exercise training reduced muscle TNF-alpha and oxidative stress (4-hydroxynonenal adducts) caused by CCO. HSP70 levels decreased with CCO (-45%), but were higher with exercise training (+348%). Mn-SOD activity, Mn-SOD protein expression, and Cu,Zn-SOD activity levels were higher in ECO than SCO by 72, 82, and 112%, respectively. GPX activity was 177% greater in ECO than in SCO. CAT trended higher (P = 0.059) in ECO compared with SCO. These data indicate that exercise training following onset of coronary artery occlusion results in recovery of critical stress proteins and reduces oxidative stress.

High-fructose diet decreases catalase mRNA levels in rat tissues

Insulin resistance and hyperinsulinemia have recently been identified as independent determinants of several risk factors for cardiovascular disease. The generation of reactive oxygen species (ROS) may play an important role as a final common mediator by which glucose and insulin resistance might contribute to development of cardiovascular disease and hypertension. The aim of the present study was to evaluate changes on mRNA expression of antioxidant enzymes [catalase, Cu-Zn superoxide dismutase (Cu-ZnSOD), MnSOD], blood pressure and metabolic parameters in insulin resistance that follow feeding normotensive Wistar rats a high-fructose-enriched diet. In our investigation 26 normal male Wistar rats were fed a high-fructose diet for 2 weeks (no.=14) or normal chow to serve as a control group (no.=12). In vivo insulin resistance was verified in a subgroup of control and fructose-fed rats by the euglycemic hyperinsulinemic clamp technique at 2 different insulin infusion rates, 29 (submaximal stimulation) and 290 (maximal stimulation) pmol/kg/min respectively. The glucose infusion rate (GIR) was not significantly different in the two groups during the submaximal infusion of insulin (1.4 +/- 0.8 mmol/kg/min in fructose-fed rats vs 1.6 +/- 0.7 mmol/kg/min in control rats, NS) while in fructose-fed rats it was significantly lower (-29.8%) than in control rats during maximal infusion of insulin (2.6 +/- 0.3 mmol/kg/min vs 3.7 +/- 0.3 mmol/kg/min, p<0.05). Fructose feeding markedly reduced the expression of catalase mRNA and Cu-ZnSOD mRNA in the liver, catalase mRNA in the heart (p<0.05). A tendency of fructose feeding to reduce the expression of antioxidant enzymes in skeletal muscle and adipose tissue was also observed (NS). Fructose feeding also increased plasma uric acid (119.9 +/- 30.4 vs 42.1 +/- 10 pmol/l, p<0.05) and systemic blood pressure (128 +/- 4 vs 109 +/- 5 mmHg, p<0.05) respect to control animals. No significant changes were observed in plasma levels of glycemia and tryglycerides. Our study suggests that in non-hyperglycemic, fructose-fed insulin-resistant rats the expression of catalase is inhibited in liver and heart. This condition might lead to higher susceptibility to oxidative stress in insulin resistance. However, an adaptive cellular response to maintain the effectiveness of intracellular signaling pathways mediated by insulin-activated hydrogen peroxide generating systems may also be hypothesized.

UPREGULATION OF ANTIOXIDANT CAPACITY BY ENDURANCE TRAINING IN PIGS FOLLOWING CHRONIC CORONARY ARTERY OCCLUSION

Growing evidence indicates that oxidative stress is associated with muscle fatigue and weakness in skeletal muscle of heart disease patients. Previously, our laboratory and others demonstrated that reactive oxygen species (ROS) and reactive nitrogen species (RNS) have the ability to inhibit key antioxidant enzymes in skeletal muscle, thus increasing susceptibility to oxidative stress. Endurance training has been shown to elevate skeletal muscle mantioxidant enzyme activities in healthy animal models. Chronic coronary artery occlusion in pigs was used to model heart disease and to test the following hypothesis: twelve weeks of treadmill endurance training will increase the antioxidant capacity in skeletal muscle in pigs with chronic coronary occlusion. Miniature Yucatan swine were divided into three groups: sedentary animals (n = 6) with coronary artery occlusion (SO); endurance trained animals (n = 6) with coronary occlusion (EO); and sedentary (n = 3) without coronary occlusion (CON). Skeletal muscle samples (triceps brachii) were extracted after a 12 week training period, and frozen in liquid nitrogen until analysis. Superoxide dismutase (total SOD, Mn-SOD isoform, and Cu, Zn-SOD isoform), glutathione peroxidase (GPX), and catalase (CAT) activities were measured. The quenching of ABTS+ radical was used as a marker of non-enzymatic antioxidant scavenging capacity (TASC). Total SOD, Mn-SOD, and Cu, Zn-SOD activities were significantly higher in EO than SO by 82.6%, 72.0%, and 112.0%, respectively. GPX activity was 176.6% greater in EO than in SO. CAT trended higher (P = 0.059) in EO when compared to SO. TASC was also significantly improved (12.7%) by exercise training over SO. All antioxidant measurements for EO were not different from CON, while SO values were lower than CON. These data indicate that endurance exercise training is critical for the protection of antioxidant capacity in pigs with chronic coronary occlusion. Grant support by NIH PO1-HL52490 and HL64931.

Activity of antioxidant enzymes in rat skeletal muscle and brown fat: effect of cold and propranolol

1. Effects of acute (6 h) and chronic (21 day) cold (6°C) exposure, as well as propranolol (15 mg/kg) on the activities of CuZnSOD, MnSOD and catalase in the rat skeletal muscle (SM) and brown adipose tissue (BAT), which are important sites of cold-induced thermogenesis, were investigated. 2. The changes in the activity of antioxidant enzymes were tissue specific and dependent on the duration of cold exposure. Thus, in the SM of acutely cold exposed rats, the activity of all antioxidant enzymes studied was elevated, whereas in the BAT the activity of both SOD s decreased and that of catalase remained unchanged. In cold acclimated rats, the activity of all the three enzymes was increased in the BAT whereas in the SM, CuZnSOD activity was enhanced, MnSOD activity decreased and catalase activity returned to the control level. 3. Propranolol also differently altered the antioxidant enzyme activity in SM and BAT, alterations being dependent on the acclimation temperature. Thus, in room acclimated rats propranolol decreased the activity of all antioxidant enzymes in SM but did not affect those in BAT. However, in the SM propranolol prevented the elevation of MnSOD and catalase activities, induced by acute cold. In cold acclimated rats propranolol inhibited CuZnSOD activity in both SM and BAT but increased that of MnSOD.

Redox regulation of antioxidant enzymes in skeletal muscle

Redox regulation of antioxidant enzymes in skeletal muscle

Antioxidant enzyme response to exercise and aging

Antioxidant enzymes play an important role in defending the cells against free radical-mediated oxidative damage. The present investigations, using rats as models, indicate that antioxidant enzyme systems undergo significant alteration during aging and in response to acute and chronic exercise. Hepatic and myocardial antioxidant enzymes show a general decline at older age, whereas activity of glutathione-related enzymes in the liver and mitochondrial enzymes in the heart increase significantly. Skeletal muscle antioxidant enzymes are uniformly elevated during aging. An acute bout of exercise can increase activity of certain antioxidant enzymes in various tissues. The mechanism for this activation is unclear. Exercise training has little effect on hepatic or myocardial enzyme systems but can cause adaptive responses in skeletal muscle antioxidant enzymes, particularly glutathione peroxidase. These findings suggest that both aging and exercise may impose an oxidative stress to the body.

Glutathione and antioxidant enzymes in skeletal muscle: effects of fiber type and exercise intensity.

Glutathione status and antioxidant enzymes in various types of rat skeletal muscle were studied after an acute bout of exercise (Ex) at different intensities. Glutathione (GSH) and glutathione disulfide (GSSG) concentrations were the highest in soleus (SO) muscle, followed by those in deep (DVL) and then superficial (SVL) portions of vastus lateralis. In DVL, but not in SO or SVL, muscle GSH increased proportionally with Ex intensity and reached 1.8 +/- 0.08 mumol/g wet wt compared with 1.5 +/- 0.03 (P < 0.05) in resting controls (R). GSSG in DVL was increased from 0.10 +/- 0.01 mumol/g wet wt in R to 0.14 +/- 0.01 (P < 0.05) after Ex. Total glutathione (GSH + GSSG) contents in DVL were also significantly elevated with Ex, whereas GSH/GSSG ratio was unchanged. Activities of GSH peroxidase (GPX), GSSG reductase (GR), and catalase (CAT) were significantly higher in SO than in DVL and SVL, but there was no difference in superoxide dismutase activity between the three muscle types. Furthermore, Ex at moderate intensities elicited significant increases in GPX, GR, and CAT activities in DVL muscle. None of the antioxidant enzymes was affected by exercise in SO. It is concluded that rat DVL muscle is particularly vulnerable to exercise-induced free radical damage and that a disturbance of muscle GSH status is indicative of an oxidative stress.

Skeletal muscle oxidative capacity, antioxidant enzymes, and exercise training

The purposes of this study were to determine whether exercise training induces increases in skeletal muscle antioxidant enzymes and to further characterize the relationship between oxidative capacity and antioxidant enzyme levels in skeletal muscle. Male Sprague-Dawley rats were exercise trained (ET) on a treadmill 2 h/day at 32 m/min (8% incline) 5 days/wk or were cage confined (sedentary control, S) for 12 wk. In both S and ET rats, catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPX) activities were directly correlated with the percentages of oxidative fibers in the six skeletal muscle samples studied. Muscles of ET rats had increased oxidative capacity and increased GPX activity compared with the same muscles of S rats. However, SOD activities were not different between ET and S rats, but CAT activities were lower in skeletal muscles of ET rats than in S rats. Exposure to 60 min of ischemia and 60 min of reperfusion (I/R) resulted in decreased GPX and increased CAT activities but had little or no effect on SOD activities in muscles from both S and ET rats. The I/R-induced increase in CAT activity was greater in muscles of ET than in muscles of S rats. Xanthine oxidase (XO), xanthine dehydrogenase (XD), and XO + XD activities after I/R were not related to muscle oxidative capacity and were similar in muscles of ET and S rats. It is concluded that although antioxidant enzyme activities are related to skeletal muscle oxidative capacity, the effects of exercise training on antioxidant enzymes in skeletal muscle cannot be predicted by measured changes in oxidative capacity.

Antioxidant enzyme systems in rat liver and skeletal muscle: Influences of selenium deficiency, chronic training, and acute exercise

The influences of selenium deficiency (Se-D), chronic training, and an acute bout of exercise on hepatic and skeletal muscle antioxidant enzymes, i.e., Superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPX), as well as glutathione S-transferase (GST) and tissue lipid peroxidation, were investigated in post-weaning male SpragueDawley rats. Se-D per se depleted GPX in both liver and skeletal muscle but had no effect on SOD or catalase activity. One hour of treadmill running (20 m/min, 0% grade and 27 m/min, 15% grade for untrained and trained rats, respectively) significantly elevated hepatic catalase and cytosolic SOD activity; more prominent activations were found in the Se-D or untrained rats, whereas skeletal muscle antioxidant enzymes were little affected. Ten weeks of training (1 h/day, 5 days/week at 27 m/min, 15% grade) increased hepatic mitochondrial SOD by 23% ( P < 0.05) in Se-D rats. Both hepatic mitochondrial and cytosolic GPX were decreased by training whereas GPX was increased twofold in skeletal muscle mitochondria. Se-independent GPX was elevated by training only in the skeletal muscle mitochondria of Se-D rats. Lipid peroxidation (malondialdehyde formation) was increased by an acute bout of exercise in hepatic mitochondria of the untrained rats and in skeletal muscle mitochondria of the Se-D rats. These data indicate that antioxidant enzymes in liver and skeletal muscle are capable of adapting to selenium deficiency and exercise to minimize oxidative injury caused by free radicals.