Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.3.3.1 (citrate synthase)
4,488 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although chronic cocaine use is cardiotoxic, its use remains problematic in athletics. Hence adaptive changes induced in the heart by superimposing chronic cocaine use on an exercise training are of interest but remain poorly understood. Therefore this study investigated the effects of cocaine treatment combined with exercise training on the metabolic and contractile properties of the heart. Male Sprague-Dawley rats were assigned to one of four groups: normal sedentary (NS, n = 6), cocaine sedentary (CS, n = 6), normal trained (NT, n = 6), and cocaine trained (CT, n = 6). Trained animals were sprint trained 4 times/week. CS and CT animals received cocaine (25 mg/kg, ip) 6 times/week, 15 min before each exercise bout and 2 additional times per week. After 12 weeks, all animals were sacrificed, and the hearts were removed and analyzed for citrate synthase activity, 3-hydroxyacyl-CoA dehydrogenase activity, Ca(2+)-activated myofibrillar ATPase activity, and myosin isoform distribution. None of the groups demonstrated altered cardiac metabolic properties, but cocaine alone and in conjunction with exercise reduced myofibrillar ATPase activity (p < 0.05) and increased expression of the low ATPase myosin isoform, V3. These data suggest that the potential of the citric acid cycle and beta-oxidation is not sensitive to chronic cocaine treatment, but the distribution of cardiac myosin among its three isoforms is affected. Furthermore, high-intensity treadmill training does not interact with cocaine to further alter these properties.
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PMID:Effects of long-term cocaine administration and exercise on cardiac metabolism and isomyosin expression. 801 90

Mechanical properties were measured in single skinned fibers from rat hindlimb muscle to test the hypothesis that the fast type IIb fiber exhibits a higher maximal shortening velocity (Vo) than the fast type IIa fiber and that the difference is directly attributable to a higher myofibrillar adenosinetriphosphatase (ATPase) activity in the type IIb fiber. Additional measurements were made to test the hypotheses that regular endurance exercise increases and decreases the Vo of the type I and IIa fiber, respectively, and that the altered Vo is associated with a corresponding change in the fiber ATPase activity. Rats were exercised by 8-12 wk of treadmill running for 2 h/day, 5 day/wk, up a 15% grade at a speed of 27 m/min. Fiber Vo was determined by the slack test, and the ATPase was measured fluorometrically in the same fiber. The myosin isozyme profile of each fiber was subsequently determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The mean +/- SE Vo (7.9 +/- 0.22 fiber lengths/s) of the type IIb fiber was significantly greater than the type IIa fiber (4.4 +/- 0.21 fiber lengths/s), and the higher Vo was associated with a higher ATPase activity (927 +/- 70 vs. 760 +/- 60 microM.min-1.mm-3). The exercise program induced cardiac hypertrophy and an approximately twofold increase in the mitochondrial marker enzyme citrate synthase. Exercise had no effect on fiber diameter or peak tension per cross-sectional area in any fiber type, but, importantly, it significantly increased (23%) both the Vo and the ATPase activity of the slow type I fiber of the soleus.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Shortening velocity and ATPase activity of rat skeletal muscle fibers: effects of endurance exercise training. 802

Mice were treated for 7-12 wk with the creatine analogue beta-guanidinopropionic acid (beta-GPA). Treatment reduced total creatine to approximately 5% of control values in soleus (SOL) and extensor digitorum longus (EDL) muscles. In both muscles from treated mice, phosphorylated beta-GPA accumulated and resting [ATP] decreased by approximately 50%. Relative to controls, cytochrome oxidase and citrate synthase activities increased significantly in EDL from treated mice, but not in SOL; creatine kinase activity decreased significantly in SOL, but not in EDL. Measurements of poststimulation energy metabolism show that the energy cost to maintain tension in SOL and EDL from treated mice was approximately 50% of that in control muscle. Relative to controls, first-order rate constants of poststimulation O2 demand were 2- and 3.6-fold greater in SOL and EDL, respectively, from treated mice. Increased economy of SOL and EDL from treated mice is consistent with previously reported changes in myosin isoenzymes. Increases in rate constants of O2 utilization in creatine-depleted muscle are inconsistent with the hypothesis that cytoplasmic or mitochondrial creatine kinase is rate limiting for cellular respiration.
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PMID:Contractile economy and aerobic recovery metabolism in skeletal muscle adapted to creatine depletion. 804 75

Heat-shock protein 72 (HSP72), the inducible isoform of the HSP70 family, is constitutively expressed in rat hindlimb muscles in proportion to the content of type I muscle fibers. To determine whether this relationship was maintained after fiber transformation, male Sprague-Dawley rats were treated with 3,5,3'-triiodo-DL-thyronine (T3) for 40 days or underwent surgical removal of the left gastrocnemius muscle, after which the left plantaris muscle was allowed to hypertrophy for 30 days. Hypertrophied plantaris muscles exhibited an increased number of type I fibers, type I myosin heavy-chain (MHC) protein, and HSP72 content compared with contralateral muscles. Soleus muscles from rats administered T3 exhibited an increased number of type II fibers, citrate synthase activity, and decreased HSP72 content compared with soleus muscles from controls. These results indicate that the relationship between HSP72 content and type I muscle fiber-MHC composition is maintained when muscles undergo fiber transformation and substantiate that HSP72 content in rat skeletal muscle is not directly linked to a muscle's oxidative capacity.
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PMID:Shifts in type I fiber proportion in rat hindlimb muscle are accompanied by changes in HSP72 content. 820 88

We examined the effect of long-term intermittent cold exposure on the fiber type composition of the predominantly type I soleus and the predominantly type IIb extensor digitorum longus (EDL) muscles of rats. Cold exposure was accomplished by submerging the rats in shoulder-deep water, maintained at 20 +/- 0.5 degrees C, for 1 h/day, 5 days/wk, for < or = 19 wk. The efficacy of the treatment was tested by subjecting both groups to 20 degrees C water for 45 min while rectal temperature (Tre) and O2 consumption (VO2) were measured. The cold-exposed group displayed a 22% smaller reduction in Tre (P < 0.05) at the end of the exposure and 23% greater VO2 (P < 0.05) during the same period. Fiber type composition was determined using routine histochemical methods for myosin-adenosinetriphosphatase. In the soleus muscle of the cold-exposed rats, the number of type IIa fibers increased 156% (P < 0.05) and the number of type I fibers decreased 24% (P < 0.05). Cold exposure had no significant influence on the fiber type composition of the EDL muscle. Cold exposure resulted in an increase in citrate synthase activity of 20 and 22% in the soleus and EDL muscles, respectively (P < 0.05). The present study demonstrates that intermittent cold exposure induces a type I-to-type IIa transformation in the soleus muscle while having no influence on the EDL muscle.
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PMID:Intermittent cold exposure causes a muscle-specific shift in the fiber type composition in rats. 837 71

During the fetal and suckling periods of mammalian development, the mother serves as the sole nutritional source for the offspring. As such, the quality of the maternal diet effects growth and development of the offspring during these periods. This study sought to determine if a maternal vitamin D deficiency altered the well characterized development of the neonatal heart. Weaned rat pups (21-day-old) were obtained from mothers who had consumed either a vitamin D-supplemented diet (3000 IU of vitamin D/kg) or a low vitamin D diet (< 200 IU of vitamin D/kg) prior to becoming pregnant and throughout pregnancy and suckling. These pups were sacrificed, hearts excised, and the hearts biochemically analysed for metabolic and contractile protein properties. The pups of dams fed the low vitamin D diet were slightly hypocalcemic relative to those on the supplemented diet (2.28 v 2.41 mumol/l, P < 0.05), had significantly lower body weights (43 v 55 g), heart weights (143 v 174 mg), citrate synthase activity (106 v 147 mumol g-1 min-1), and 3-hydroxyacyl CoA dehydrogenase activity (59 v 91 mumol g-1 min-1). Hexokinase activity (1.98 v 2.02 mumol g-1 min-1), and the distribution of cardiac myosin among its three isoforms (> 85% V1), were unaffected by this dietary deficiency, however myofibrillar protein content was approximately 15% lower in the experimental hearts. These data demonstrate that maternal consumption of a low vitamin D diet results in a general but significant slowing of neonatal cardiac development.
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PMID:Maternal consumption of a low vitamin D diet retards metabolic and contractile development in the neonatal rat heart. 853 Dec 6

Skeletal muscle sarcolemmal vesicles from control (C) and hindlimb suspended (S) rats were used to investigate the effect of unweighting on the lactate transporter activity. Sarcolemmal preparations were not different between the two groups. The efficiency of 4 weeks of hindlimb suspension was confirmed by a 40% decrease of citrate synthetase activity and a shift towards faster myosin isoforms in soleus muscle. The time course of 1 mM lactate uptake showed that the equilibrium was reached faster in group C (20 s) than in group S (40 s). The initial rate of 1 mM of lactate uptake decreased significantly (p < 0.05) after 4 weeks of hindlimb suspension. The initial rate of 50 mM lactate uptake did not differ significantly between the two groups. We conclude that 4 weeks of unweighting decreases significantly the skeletal muscle sarcolemmal lactate transport activity in rats. This result suggests that the level of physical activity probably plays a role on lactate transport regulation in muscle.
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PMID:[Effect of hypodynamia on initial speed of lactate transport in skeletal muscle sarcolemmal vesicles in rats]. 859 Feb 33

A condition similar to insulin-dependent diabetes mellitus (IDDM) was induced in male CD-1 mice by injection of streptozotocin (STZ). Five weeks after treatment, the fast-twitch extensor digitorum longus (EDL) and slow-twitch soleus (SOL) muscles were isolated for analysis. Phosphorous metabolites were quantified by 31P-NMR and HPLC, native myosin was characterized electrophoretically, and activities of metabolic enzymes were measured spectrophotometrically. Relative to control animals, STZ-diabetes resulted in a significant 32% decrease in the FM1 isoform of myosin in EDL and a 24% decrease in IM myosin of SOL. Mass-specific activities of phosphofructokinase, citrate synthase, and cytochrome oxidase were significantly lower in SOL from STZ-diabetic mice than in controls by 23, 18, and 36%, respectively. Intracellular ATP was significantly lower in SOL from STZ-diabetic mice than in controls (3.44 +/- 0.20 mumol g-1 wet weight vs. 4.61 +/- 0.20 mumol g-1, respectively), as was creatine phosphate (11.98 +/- 0.80 mumol g-1 wet weight vs. 14.22 +/- 0.44 mumol g-1). In contrast to results from SOL, there were no significant changes in phosphorus metabolites or enzyme activity in EDL. These results show that the effects of IDDM on levels of phosphorus containing metabolites and maximal activities of key regulatory enzymes in muscle are markedly fiber-type specific. It is suggested that the muscle type-specific effects of STZ-diabetes may be a consequence of differential accumulation of intracellular fatty acids.
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PMID:Responses of mouse fast and slow skeletal muscle to streptozotocin diabetes: myosin isoenzymes and phosphorous metabolites. 859 19

Chronic electrical stimulation of skeletal muscle at 10 Hz induces fast-to-slow fiber type transformation. Does a lower aggregate amount of activity lead to a less complete transformation, or does it produce the same transformation over a longer time course? We examined this question by subjecting adult rabbit tibialis anterior and extensor digitorum longus muscles to continuous stimulation at 2.5 Hz for 2-12 wk. Most of the fibers acquired the histochemical and immunocytochemical characteristics of type 2A, not type 1, fibers. There was a corresponding rise in oxidative activity, but this was accompanied by a marked decline in anaerobic glycolysis. The activities of hexokinase and 3-oxoacid CoA-transferase stopped increasing after 2 wk, glutamate oxaloacetate transaminase after 4 wk, and beta-hydroxyacyl-CoA dehydrogenase after 6 wk of stimulation. Succinate dehydrogenase, citrate synthase, lactate dehydrogenase, and creatine phosphokinase continued to change up to 12 wk of stimulation. Changes in enzyme activity were not as rapid or as marked as those observed for stimulation at 10 Hz, and none showed the typical two-phase response of oxidative enzyme activities to stimulation at 10 Hz. The latter may therefore be dependent on induction of type 1 myosin isoforms.
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PMID:Induction of a fast-oxidative phenotype by chronic muscle stimulation: histochemical and metabolic studies. 877 59

A population of muscle fibers containing a myosin heavy-chain isoform IId (or 2x) has recently been identified in rat muscle. The purpose of this study was to histochemically determine the relative population and size of muscle fibers composed of type IID/X fibers as well as type I, IIA, and IIB fibers to estimate the absolute mass of the different types of fibers in rat muscle. In addition, muscle citrate synthase activity was measured to determine the relationship between fiber composition and muscle oxidative capacity. Seventy-six muscles or muscle parts from the face, neck, shoulder, arm, trunk, hip, thigh, and leg of three adult (4.5-5 mo of age) male Sprague-Dawley rats were removed, weighed, and frozen for histochemical and biochemical analyses. The data demonstrated that type IIB fibers make up 71% of the total muscle mass, type IID/X fibers 18%, type IIA fibers 5%, and type I fibers 6%. The mean cross-sectional area across all muscles was 5,078 +/- 175 microns 2 for type IIB fibers, 3,078 +/- 105 microns2 for type IID/X fibers, 2,045 +/- 80 microns2 for type IIA fibers, and 1,898 +/- 90 microns2 for type I fibers. Citrate synthase activity, an indicator of muscle mitochondrial content, was most closely related to the population of type IIA fibers and was in the rank order of type IIA > I > IID/X > IIB. NADH-tetrazolium reductase staining intensity also confirmed this order. These data demonstrate that type IID/X fibers make up a significant portion of the adult rat muscle mass and are intermediate to type IIA and IIB fibers in regard to fiber size and oxidative potential.
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PMID:Composition and size of type I, IIA, IID/X, and IIB fibers and citrate synthase activity of rat muscle. 884 13


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