Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.3.3.1 (citrate synthase)
 4,488 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this study was to determine whether cardiac biochemical adaptations are induced by chronic exercise training (ET) of miniature swine. Female Yucatan miniature swine were trained on a treadmill or were cage confined (C) for 16-22 wk. After training, the ET pigs had increased exercise tolerance, lower heart rates during exercise at submaximal intensities, moderate cardiac hypertrophy, increased coronary blood flow capacity, and increased oxidative capacity of skeletal muscle. Myosin from both the C and ET hearts was 100% of the V3 isozyme, and there were no differences between the myosin adenosine triphosphatase (ATPase) or myofibrillar ATPase activities of C and ET hearts. Also, the sarcoplasmic reticulum Ca(2+)-ATPase activity and Na(+)-Ca2+ exchange activity of sarcolemmal vesicles were the same in cardiac muscle of C and ET hearts. Finally, the glycolytic and oxidative capacity of ET cardiac muscle was not different from control, since phosphofructokinase, citrate synthase, and 3-hydroxyacyl-CoA dehydrogenase activities were the same in cardiac tissue from ET and C pigs. We conclude that endurance exercise training does not provide sufficient stress on the heart of a large mammal to induce changes in any of the three major cardiac biochemical systems of the porcine myocardium: the contractile system, the Ca2+ regulatory systems, or the metabolic system.
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PMID:Biochemical characterization of exercise-trained porcine myocardium. 183 67

Male rats, aged 17 weeks at the end of experiments, were divided into four groups. Two groups lived in normal cage conditions with or without extra load (20% of the body weight) and two groups were trained by running with or without extra load for 8 weeks. Oxidation rates of succinate, glutamate + malate, palmitoylcarnitine, and pyruvate, and the activities of lactate dehydrogenase, citrate synthase, isocitrate dehydrogenase and cytochrome oxidase were measured in homogenates of the right ventricle and in those of the subendocardial and subepicardial layers of the left ventricle. Oxidation rates of succinate and palmitoylcarnitine tended to be higher in the subendocardium than in the subepicardium of sedentary control animals (p less than 0.1 and p less than 0.05, respectively). Transmural differences of succinate and palmitoylcarnitine oxidation rates were even more clear after running training (p less than 0.01 and p less than 0.05, respectively), after carrying extra load (p less than 0.001 and p less than 0.001, respectively) and after training carrying extra load (p less than 0.001 and p less than 0.05, respectively). Training also enhanced pyruvate oxidation rate in the subendocardium. Oxidation rates of all substrates were lower in the right ventricle than in the left ventricle. In control animals there were no regional differences in the myocardial enzyme activities and the training- or extra-load-induced changes were modest compared with the changes in the oxidation rates. The most significant change was the training-induced enhancement in the lactate dehydrogenase activity of the subendocardium (p less than 0.001 vs subepicardium). These results show greater subendocardial than subepicardial oxidation rates of certain substrates in the normal heart. These results also suggest that the myocardium adapts to increased work by increasing the subendocardial oxidation rate of some but not all substrates, indicating further that there may be qualitative mitochondrial differences in the different regions of the heart.
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PMID:Regional differences of substrate oxidation capacity in rat hearts: effects of extra load and endurance training. 207 98

Rats exposed to head-down suspension (HDS) exhibit reductions in maximal O2 consumption (VO2max) and atrophy of select hindlimb muscles. This study tested the hypothesis that an endocrine-deficient rat exposed to HDS would not exhibit reductions in VO2max or hindlimb muscle mass. Hypophysectomized (HYPX) and sham-operated (SHAM) rats were tested for VO2max before and after 28 days of HDS or cage control (CC) conditions. No significant reductions in VO2max were observed in HYPX rats. In contrast, SHAM-HDS rats exhibited a significant reduction in absolute (-16%) and relative (-29%) measures of aerobic capacity. Time course experiments revealed a reduction in VO2max in SHAM-HDS rats within 7 days, suggesting that cardiovascular adjustments to HDS occurred in the 1st wk. HDS was associated with atrophy of the soleus (-42%) in SHAM rats, whereas HYPX rats exhibited atrophy of the soleus (-36%) and plantaris (-13%). SHAM-HDS rats had significantly lower (-38%) soleus citrate synthase activities per gram muscle mass than SHAM-CC, but no significant differences existed between HYPX-HDS and -CC rats. HDS rats had an impaired ability to thermoregulate, as indicated by significantly greater temperature increases per unit run time, compared with their CC counterparts. Pretreatment plasma epinephrine levels were significantly lower in HYPX than in SHAM rats. Norepinephrine concentration was similar for all groups except HYPX-HDS, in which it was significantly higher. HDS had no significant effect on thyroxine or triiodothyronine. SHAM-HDS rats had significantly lower concentrations of testosterone and growth hormone.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Metabolic responses to head-down suspension in hypophysectomized rats. 812 95

To investigate the effects of exercise training and immobilization on peak O2 uptake (VO2) and effective O2 diffusive conductance (DO2) in skeletal muscle, three groups of purpose-bred hounds [control (C), exercise trained (E), and immobilized (I)] were studied. Group E exercised on a treadmill 1 h/day, 5 days/wk for 8 wk, while groups C and I were cage confined for 8 wk, with group I undergoing left hindlimb immobilization for the last 3 wk. Thereafter, each dog's left gastrocnemius was surgically isolated, pump perfused, and electrically stimulated to elicit peak VO2 in situ at three levels of arterial oxygenation. O2 delivery [(arterial O2 concentration x muscle blood flow)/100 g muscle] was kept constant among the three groups at each level of arterial oxygenation. Compared with group C, peak VO2/100 g muscle was 38, 33, and 19% greater and DO2/100 g muscle was 71, 75, and 68% greater during normoxia, moderate hypoxia, and severe hypoxia, respectively, in group E (P < 0.02), whereas no differences from control were found in group I. We conclude that O2 delivery is not the unique determinant of peak VO2 and that exercise training improves the functional blood-tissue gas exchange properties of the muscle itself. Immobilization sufficient to reduce muscle weight by 31% and citrate synthase activity by 68% has no effect on peak VO2/100 g muscle or DO2/100 g muscle.
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PMID:Effects of training and immobilization on VO2 and DO2 in dog gastrocnemius muscle in situ. 851 85

To gain insight into diaphragm functional heterogeneity, blood flow (expressed as ml.min-1 x 100 g-1) was measured using radiolabeled microspheres in the ventral, medial, and dorsal regions of the costal diaphragm and in the crural diaphragm of sedentary control (S) and exercise trained (ET) female Wistar-Kyoto rats at rest and during treadmill exercise. ET animals had performed moderate intensity exercise training on a motorized treadmill (22 m/min, 10% grade, 60 min/d) for 12 months, while S were cage-confined. The efficacy of exercise training was demonstrated by a 12% increase (P < 0.05) in ventricular weight-to-body weight ratio and increases (P < 0.05) in citrate synthase activity in hindlimb skeletal muscles of ET. At rest, blood flow in the ventral costal diaphragm (16 +/- 1) averaged approximately 61% of that in the medial (26 +/- 3) and dorsal (25 +/- 2) costal regions (P = 0.035), and crural diaphragm flow was 23 +/- 3. During treadmill exercise (5 min at 22 m/min, 10% incline), blood flow increased an average of 5-fold (P < 0.001) throughout the diaphragm, but the heterogeneous flow pattern persisted; i.e., blood flow remained lower (P = 0.003) in the ventral region (77 +/- 7) than either the medial (135 +/- 15) or dorsal (127 +/- 11) costal regions. Flow in the crural diaphragm during exercise was intermediate (105 +/- 9). Exercise training did not alter either the magnitude of blood flows or the flow distribution pattern within the diaphragm. Citrate synthase activity was two-fold that of the plantaris muscle and was uniform across the ventral, medial, and dorsal costal and the crural diaphragm of a second group of age-matched rats (P = 0.57). These data demonstrate that, although oxidative capacity is uniform throughout the diaphragm, there is a significant regional heterogeneity of blood flow within the rat diaphragm both at rest and during locomotory exercise. The greater flow in the medial and dorsal regions of the costal diaphragm suggests that these regions sustain a greater portion of the inspiratory work load at rest and during exercise compared to the ventral region.
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PMID:Costal diaphragm blood flow heterogeneity at rest and during exercise. 857 Sep 19

The objective of this study was to test the hypothesis that an endurance training program designed to produce recruitment of all extensor muscle fiber types during each exercise bout would stimulate capillary angiogenesis throughout rat gastrocnemius and soleus muscles. Male Sprague-Dawley rats were exercise trained 5 days/wk for 12-14 wk with exercise bouts consisting of a combination of high intensity (32 m/min on a 15% incline) and long duration (90 min/day). On completion of high-intensity endurance training (HIET) or cage activity [sedentary (Sed)], rat hindquarters were vascularly isolated and perfusion fixed with a modified Karnovsky's fixative. Capillary supply was measured in soleus and gastrocnemius muscles by using Olympus Cue 2 image-analyzer software. Capillary supply was reflected in measurements of capillary-to-fiber ratio, capillary numerical density, capillary surface area density, and capillary volume density on transversely cut tissue sections. HIET increased citrate synthase activity by 20 and 42% in the medial and long heads of the triceps brachii, respectively. Sarcomere lengths were similar in gastrocnemius and soleus muscles of Sed and HIET rats after fixation. All four indexes of capillary supply were significantly greater throughout the gastrocnemius muscle of HIET rats compared with Sed values. The relative increase in capillarity was greater in white than in red gastrocnemius muscle of HIET rats. HIET also increased capillary supply of soleus muscle. However, only capillary numerical density was statistically greater (19%) in HIET soleus compared with Sed. These results support the hypothesis that this training program would produce an increase in capillary supply in all extensor muscles.
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PMID:Regional changes in capillary supply in skeletal muscle of high-intensity endurance-trained rats. 887 26

We examined the extent of morphological alterations and the myosin heavy chain (MHC) distribution in the rat soleus muscle after a 4-week period of spontaneous recovery or retraining after hindlimb suspension (HS). Moreover, we tested the hypothesis that dantrolene sodium, which affects the flux of calcium over the sarcoplasmic reticulum membrane, was able to attenuate muscle damage. Three groups of rats were submitted to 3 weeks of HS, followed by either 4 weeks of unrestricted cage activity (HC, n = 7), or running training for the same period and were compared to age-matched animals (C, n = 8). Trained rats were treated with either placebo or dantrolene sodium (HTP, HTD, n = 8 each, respectively). Four weeks after HS recovery, the percentage of myofibres with internal nuclei (%in) was determined by histological staining with hematoxylin and eosin. %in was affected by the individual rat (P < 0.001), and was higher in the mid-belly region of the muscle (P < 0.05). Muscle damage, as estimated by %in, was more extensive in trained rats (i.e. HTP and HTD) than in HC animals (23% and 12%, respectively). Moreover, dantrolene sodium tended to exert a protective effect on training-induced muscle injury. A 12% increase in type I MHC was observed in both HTP and HTD rats, in comparison with group C animals (P < 0.001). The relative proportion of type-I MHC was inversely correlated with %in (r = -0.65, P < 0.001). Running recovery led to an increased citrate synthase activity in comparison with that of C or HC rats. In conclusion, the present findings demonstrate that running recovery from HS increases the incidence of muscle damage, and that dantrolene sodium administration has only limited protective effects against exercise-induced muscle injury.
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PMID:Muscle damage induced by running training during recovery from hindlimb suspension: the effect of dantrolene sodium. 936 82

This study evaluated whether daily exercise would enhance the peripheral collateral vessel development found in response to exogenous basic fibroblast growth factor (bFGF) infusion. After bilateral femoral occlusion, male Sprague-Dawley rats (approximately 325 g) received intra-arterial infusions of either bFGF (1 microg/day; n = 15) or carrier solution (n = 13) via osmotic pumps for 2 wk. Subgroups of each treatment were kept sedentary (cage activity) or trained by walking at 20 m/min at 15% grade, two times a day, 5 days/wk for 4 wk. Training markedly increased citrate synthase activity in the active muscle (P < 0.001). Muscle function and blood flows (85Sr microsphere) were evaluated using an isolated hindquarter perfused at 100 mmHg via the abdominal aorta. The significant increase in blood flow to the entire hindlimb in the sedentary animals, caused by bFGF infusion (P < 0.05), was further increased (P < 0.01) in the bFGF-trained group. The quantitatively largest increases in blood flows were observed in the collateral-dependent tissues of the distal hindlimb. Blood flows to the entire calf muscle group increased approximately 140% in carrier-trained (P < 0.001), approximately 180% in bFGF sedentary (P < 0.001), and approximately 240% in the bFGF-trained (P < 0.001) groups compared with the carrier sedentary group. The increases in collateral blood flow were functionally important, as improvements in calf muscle performance correlated with measured blood flows. Our results demonstrate that exogenous bFGF administration in combination with a moderate-intensity exercise program greatly increases collateral-dependent blood flow and improves muscle performance. That physical activity enriched the bFGF response is consistent with the hypothesis that hemodynamic factors are important contributors to collateral vessel enlargement.
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PMID:Exercise training enhances basic fibroblast growth factor-induced collateral blood flow. 984 32

Aerobic exercise training evokes adaptations in the myocardial contractile machinery that enhance cardiac functional capacity; in comparison, the effects of training on the myocardium's energy generating pathways are less well characterized. This study tested the hypothesis that aerobic exercise training can increase the capacities of the major pathways of intermediary metabolism in canine myocardium. Mongrel dogs were conditioned by a 9-week treadmill running program or cage rested for 4 weeks. Exercise conditioning was evidenced by 26% and 22% decreases (P<0.05) in respective heart rates at rest and during submaximal exercise and by a 40% increase (P<0.05) in citrate synthase (CS) activity of the vastus lateralis. Glycolytic, TCA cycle, and beta-oxidative enzymes were assayed in myocardial extracts at 37 degrees C. Relative to sedentary controls, training increased glyceraldehyde 3-phosphate dehydrogenase (GAPDH) activity by 49% in left and 33% in right ventricle, and pyruvate kinase, CS, and 3-hydroxyacyl CoA dehydrogenase (HADH) activities by 74%, 91%, and 77%, respectively, in left ventricle (P<0.05). Immunoblotting further confirmed that training increased left ventricular contents of CS and GAPDH. Other measured enzymes (hexokinase, phosphofructokinase, lactate dehydrogenase, alpha-ketoglutarate dehydrogenase, malate dehydrogenase) were not altered by training in either ventricle. Kinetic analyses revealed increased maximum rates but unaltered substrate affinities of GAPDH, CS and HADH following training. Thus, aerobic exercise training augments the intermediary metabolic capacity of canine myocardium by selectively increasing the concentrations of regulatory enzymes of glycolysis and oxidative metabolism.
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PMID:Exercise training enhances glycolytic and oxidative enzymes in canine ventricular myocardium. 1088 45

Heat shock protein 72 (HSP72), the inducible isoform of the HSP70 family, is synthesized in exercised rat muscles and in the ischaemic heart. To determine the isolated and combined effects of chronic ischaemia and repeated exercise on skeletal muscle HSP72 expression, male Wistar rats were subjected to unilateral occlusion of the iliac artery. Beginning 1 week after ischaemia, half the rats were exercised on a motor-driven treadmill once a day, 5 days/week, the other half were restricted to cage activity. Rats were sacrificed after 2, 4, or 8 weeks of endurance training, together with the age-matched sedentary rats. Tissue samples were obtained from the plantaris and the red portion of the quadriceps of both hind-limbs. Endurance-trained rats displayed significantly increased HSP72 levels in skeletal muscles. Occlusion of iliac artery did not affect the HSP72 level in muscle from sedentary rats but enhanced that in the trained rats. Mitochondrial oxidative capacity, as assessed from cytochrome oxidase and citrate synthase activities, decreased during growth in sedentary animals, but was significantly improved by endurance training. Nevertheless, increased oxidative capacity induced by endurance training was partially prevented by arterial occlusion. It is concluded that both HSP72 levels and mitochondrial oxidative capacity are affected by ischaemia and training but these changes are not necessarily related. Whereas superimposition of chronic exercise on peripheral arterial insufficiency increased HSP72 levels, our results demonstrate that endurance training even for extended period of time is not effective for improving oxidative capacity of ischaemic muscle.
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PMID:Skeletal muscle HSP72 level during endurance training: influence of peripheral arterial insufficiency. 1104 59


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