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:1.9.3.1 (cytochrome oxidase)
8,822 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Selective breeding is an important tool in behavioral genetics and evolutionary physiology, but it has rarely been applied to the study of exercise physiology. We are using artificial selection for increased wheel-running behavior to study the correlated evolution of locomotor activity and physiological determinants of exercise capacity in house mice. We studied enzyme activities and their response to voluntary wheel running in mixed hindlimb muscles of mice from generation 14, at which time individuals from selected lines ran more than twice as many revolutions per day as those from control (unselected) lines. Beginning at weaning and for 8 wk, we housed mice from each of four replicate selected lines and four replicate control lines with access to wheels that were free to rotate (wheel-access group) or locked (sedentary group). Among sedentary animals, mice from selected lines did not exhibit a general increase in aerobic capacities: no mitochondrial [except pyruvate dehydrogenase (PDH)] or glycolytic enzyme activity was significantly (P < 0.05) higher than in control mice. Sedentary mice from the selected lines exhibited a trend for higher muscle aerobic capacities, as indicated by higher levels of mitochondrial (cytochrome-c oxidase, carnitine palmitoyltransferase, citrate synthase, and PDH) and glycolytic (hexokinase and phosphofructokinase) enzymes, with concomitant lower anaerobic capacities, as indicated by lactate dehydrogenase (especially in male mice). Consistent with previous studies of endurance training in rats via voluntary wheel running or forced treadmill exercise, cytochrome-c oxidase, citrate synthase, and carnitine palmitoyltransferase activity increased in the wheel-access groups for both genders; hexokinase also increased in both genders. Some enzymes showed gender-specific responses: PDH and lactate dehydrogenase increased in wheel-access male but not female mice, and glycogen phosphorylase decreased in female but not in male mice. Two-way analysis of covariance revealed significant interactions between line type and activity group; for several enzymes, activities showed greater changes in mice from selected lines, presumably because such mice ran more revolutions per day and at greater velocities. Thus genetic selection for increased voluntary wheel running did not reduce the capability of muscle aerobic capacity to respond to training.
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PMID:Effects of voluntary activity and genetic selection on muscle metabolic capacities in house mice Mus domesticus. 1100 2

The influence of thyroxine on activity of enzymes of energy metabolism (hexokinase, phosphofructokinase, pyruvate kinase, laktate dehydrogenase, glucose-6-phosphate dehydrogenase, NADP-isocitrate dehydrogenase, cytochrome-c oxidase) and antioxidative system (glutathione peroxidase, glutathione reductase, superoxide dismutase) of neonatal piglet neutrophils was investigated. It has been found, that after durable injections of hormone (4 mg/kg body weight) the increase of glycolytic enzymes activities as well as aerobic energy pathway catalyzers took place. Simultaneously the augmentation of superoxide dismutase reaction occurred after the thyroxine treatment. Such effect might represent an important link in compensatory mechanism, which prevents the destructive action of reactive oxygen species.
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PMID:[The effect of thyroxine on the enzymatic activity of the energy metabolism and antioxidant system in the neutrophilic granulocytes of piglets]. 1105 92

Numerous metabolic adaptations occur in the heart after birth. Important transcription factors that regulate expression of the glycolytic and mitochondrial oxidative genes are hypoxia-inducible factors (HIF-1alpha and -2alpha) and nuclear respiratory factor-1 (NRF-1). The goal of this study was to examine expression of HIF-1alpha, HIF-2alpha, and NRF-1 and the genes they regulate in pre- and postnatal myocardium. Ovine right and left ventricular myocardium was obtained at four time points: 95 and 140 d gestation (term = 145 d) and 7 d and 8 wk postnatally. Steady-state mRNA and protein levels of HIF-1alpha and NRF-1 and protein levels of HIF-2alpha were measured along with mRNA of HIF-1alpha-regulated genes (aldolase A, alpha- and beta-enolase, lactate dehydrogenase A, liver and muscle phosphofructokinase) and NRF-1-regulated genes (cytochrome c, Va subunit of cytochrome oxidase, and carnitine palmitoyltransferase I ). HIF-1alpha protein was present in fetal myocardium but dropped below detectable levels at 7 d postnatally. HIF-2alpha protein levels were similar at the four time points. Steady-state mRNA levels of alpha-enolase, lactate dehydrogenase A, and liver phosphofructokinase declined significantly postnatally. Aldolase A, beta-enolase, and muscle phosphofructokinase mRNA levels increased postnatally. Steady-state mRNA and protein levels of NRF-1 decreased postnatally in contrast to the postnatal increases in cytochrome c, subunit Va of cytochrome oxidase, and carnitine palmitoyltransferase I mRNA levels. The in vivo postnatal regulation of enzymes encoding glycolytic and mitochondrial enzymes is complex. As transactivation response elements for the genes encoding metabolic enzymes continue to be characterized, studies using the fetal-to-postnatal metabolic transition of the heart will continue to help define the in vivo role of these transcription factors.
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PMID:Metabolic adaptation of the fetal and postnatal ovine heart: regulatory role of hypoxia-inducible factors and nuclear respiratory factor-1. 1214 6

Type 2 diabetes has been related to a decrease of mitochondrial DNA (mtDNA) content. In this study, we show increased expression of the peroxisome proliferator-activated receptor-alpha (PPARalpha) and its target genes involved in fatty acid metabolism in skeletal muscle of Zucker Diabetic Fatty (ZDF) (fa/fa) rats. In contrast, the mRNA levels of genes involved in glucose transport and utilization (GLUT4 and phosphofructokinase) were decreased, whereas the expression of pyruvate dehydrogenase kinase 4 (PDK-4), which suppresses glucose oxidation, was increased. The shift from glucose to fatty acids as the source of energy in skeletal muscle of ZDF rats was accompanied by a reduction of subunit 1 of complex I (NADH dehydrogenase subunit 1, ND1) and subunit II of complex IV (cytochrome c oxidase II, COII), two genes of the electronic transport chain encoded by mtDNA. The transcript levels of PPARgamma Coactivator 1 (PGC-1) showed a significant reduction. Treatment with troglitazone (30 mg/kg/day) for 15 days reduced insulin values and reversed the increase in PDK-4 mRNA levels, suggesting improved insulin sensitivity. In addition, troglitazone treatment restored ND1 and PGC-1 expression in skeletal muscle. These results suggest that troglitazone may avoid mitochondrial metabolic derangement during the development of diabetes mellitus 2 in skeletal muscle.
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PMID:Impaired expression of NADH dehydrogenase subunit 1 and PPARgamma coactivator-1 in skeletal muscle of ZDF rats: restoration by troglitazone. 1456 25

Beta-agonists and glucocorticoids are frequently coprescribed for chronic asthma treatment. In this study the effects of 4 week treatment with beta-agonist clenbuterol (CL) and glucocorticoid dexamethasone (DEX) on respiratory (diaphragm and parasternal) and limb (soleus and tibialis) muscles of the mouse were studied. Myosin heavy chain (MHC) distribution, fibres cross sectional area (CSA), glycolytic (phosphofructokinase, PFK; lactate dehydrogenase, LDH) and oxidative enzyme (citrate synthase, CS; cytochrome oxidase, COX) activities were determined. Muscle samples were obtained from four groups of adult C57/B16 mice: (1) Control (2) Mice receiving CL (CL, 1.5 mg kg(-1) day(-1) in drinking water) (3) Mice receiving DEX (DEX, 5.7 mg kg(-1) day(-1) s.c.) (4) Mice receiving both treatments (DEX + CL). As a general rule, CL and DEX showed opposite effects on CSA, MHC distribution, glycolytic and mitochondrial enzyme activities: CL alone stimulated a slow-to-fast transition of MHCs, an increase of PFK and LDH and an increase of muscle weight and fibre CSA; DEX produced an opposite (fast-to-slow transition) change of MHC distribution, a decrease of muscle weight and fibre CSA and in some case an increase of CS. The response varied from muscle to muscle with mixed muscles, as soleus and diaphragm, being more responsive than fast muscles, as tibialis and parasternal. In combined treatments (DEX + CL), the changes induced by DEX or CL alone were generally minimized: in soleus, however, the effects of CL predominated over those of DEX, whereas in diaphragm DEX prevailed over CL. Taken together the results suggest that CL might counteract the unwanted effects on skeletal muscles of chronic treatment with glucocorticoids.
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PMID:Clenbuterol antagonizes glucocorticoid-induced atrophy and fibre type transformation in mice. 1510 14

Cellular energy metabolism is altered in sepsis as a consequence of dysfunction of mitochondrial electron transport and glycolytic pathways. The purpose of the present study was to determine whether sepsis is associated with compensatory increases in gene expression of electron transport chain and glycolytic pathway proteins or, alternatively, whether gene expression decreases in sepsis, contributing to abnormalities in energy metabolism. Studies were performed using diaphragms from control and endotoxin-treated (8 mg x kg(-1) x day(-1)) rats; at 48 h after endotoxin administration, animals were killed. Microarrays and RNAse protection assays were used to assess the expression of several electron transport chain components (cytochrome-c oxidase subunits Cox 5A, Cox 5B, and Cox 6A, ATP synthase, and ATP synthase subunit 5B) and of the rate-limiting enzyme for glycolysis, phosphofructokinase (PFK). Western blotting was used to assess protein levels for these electron transport chain subunits and PFK. Activity assays were used to assess electron transport chain and phosphofructokinase function. We found that sepsis evoked 1) a downregulation of genes encoding all examined electron transport chain components (e.g., cytochrome-c oxidase 5A decreased 45 + 7%, P < 0.01) and PFK (P < 0.001), 2) reductions in protein levels for these electron transport chain subunits and PFK (P < 0.05 for each), and 3) decreases in mitochondrial state 3 respiration rates and phosphofructokinase enzyme activity (P < 0.01 for each comparison). We speculate that these sepsis-induced reductions in the expression of genes encoding critical electron transport and glycolytic proteins contribute to the development and persistence of sepsis-induced abnormalities in cellular energy metabolism.
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PMID:Downregulation of diaphragm electron transport chain and glycolytic enzyme gene expression in sepsis. 1610 21

We hypothesized that specific muscular transcript level adaptations participate in the improvement of endurance performances following intermittent hypoxia training in endurance-trained subjects. Fifteen male high-level, long-distance runners integrated a modified living low-training high program comprising two weekly controlled training sessions performed at the second ventilatory threshold for 6 wk into their normal training schedule. The athletes were randomly assigned to either a normoxic (Nor) (inspired O2 fraction = 20.9%, n = 6) or a hypoxic group exercising under normobaric hypoxia (Hyp) (inspired O2 fraction = 14.5%, n = 9). Oxygen uptake and speed at second ventilatory threshold, maximal oxygen uptake (VO2 max), and time to exhaustion (Tlim) at constant load at VO2 max velocity in normoxia and muscular levels of selected mRNAs in biopsies were determined before and after training. VO2 max (+5%) and Tlim (+35%) increased specifically in the Hyp group. At the molecular level, mRNA concentrations of the hypoxia-inducible factor 1alpha (+104%), glucose transporter-4 (+32%), phosphofructokinase (+32%), peroxisome proliferator-activated receptor gamma coactivator 1alpha (+60%), citrate synthase (+28%), cytochrome oxidase 1 (+74%) and 4 (+36%), carbonic anhydrase-3 (+74%), and manganese superoxide dismutase (+44%) were significantly augmented in muscle after exercise training in Hyp only. Significant correlations were noted between muscular mRNA levels of monocarboxylate transporter-1, carbonic anhydrase-3, glucose transporter-4, and Tlim only in the group of athletes who trained in hypoxia (P < 0.05). Accordingly, the addition of short hypoxic stress to the regular endurance training protocol induces transcriptional adaptations in skeletal muscle of athletic subjects. Expressional adaptations involving redox regulation and glucose uptake are being recognized as a potential molecular pathway, resulting in improved endurance performance in hypoxia-trained subjects.
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PMID:Exercise training in normobaric hypoxia in endurance runners. III. Muscular adjustments of selected gene transcripts. 1654 Jul 10

Marbling is an important criterion for beef quality grading in many countries. The purpose of the current study was to utilize the natural genetic variation to identify major metabolic indicators of marbling in cattle differing in genotypes. Rectus abdominis (RA, oxidative), semitendinosus (glycolytic), and longissimus thoracis (LT, oxido-glycolytic) muscles were taken from steers of different genotypes that expressed high [Angus, n = 16; and crossbred (Angus x Japanese Black), n = 10] or low (Limousin, n = 12) levels of marbling in their meat. Muscles from Angus and crossbred steers were characterized, as expected, by a greater triacylglycerol (TAG) content (P < 0.001) and also by greater protein contents of fatty acid-binding protein specific for heart and muscles (H-FABP; P < 0.001 for RA and P < 0.05 for LT muscle) or for adipocytes (A-FABP; P < 0.001 for RA and LT muscles). Moreover, oxidative enzyme activities (beta-hydroxyacyl-CoA dehydrogenase, citrate synthase, isocitrate dehydrogenase, cytochrome-c oxidase) were greater (P < 0.01 to 0.001) in the 3 muscles studied, whereas glycolytic enzyme activities (phosphofructokinase and lactate dehydrogenase) were lower (P < 0.001) in RA muscle in Angus and crossbred steers compared with Limousin steers. Significant correlations were observed between TAG content and H- and A-FABP protein contents, and oxidative (r > or = +0.55, P < 0.001) or glycolytic enzyme activities (r > or = -0.47, P < 0.001), when the 3 genotypes and muscles studied were considered as a whole. In addition, A-FABP protein content and some oxidative enzyme activities were significantly correlated with TAG content independently of the genotype and muscle effects. In conclusion, A-FABP protein content, as well as oxidative enzyme activities, may be used as indicators of the ability of steers from extreme genotypes to deposit intramuscular fat.
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PMID:Adipocyte fatty acid-binding protein and mitochondrial enzyme activities in muscles as relevant indicators of marbling in cattle. 1756 66

To examine the effects of repetitive bouts of heavy exercise on the maximal activities of enzymes representative of the major metabolic pathways and segments, 13 untrained volunteers [peak aerobic power (Vo(2 peak)) = 44.3 +/- 2.3 ml.kg(-1).min(-1)] cycled at approximately 91% Vo(2 peak) for 6 min once per hour for 16 h. Maximal enzyme activities (V(max), mol.kg(-1).protein.h(-1)) were measured in homogenates from tissue extracted from the vastus lateralis before and after exercise at repetitions 1 (R1), 2 (R2), 9 (R9), and 16 (R16). For the mitochondrial enzymes, exercise resulted in reductions (P < 0.05) in cytochrome-c oxidase (COX, 14.6%), near significant reductions in malate dehydrogenase (4.06%; P = 0.06) and succinic dehydrogenase (4.82%; P = 0.09), near significant increases in beta-hydroxyacyl-CoA dehydrogenase (4.94%; P = 0.08), and no change in citrate synthase (CS, 2.88%; P = 0.37). For the cytosolic enzymes, exercise reduced (P < 0.05) V(max) in hexokinase (Hex, 4.4%), creatine phosphokinase (9.0%), total phosphorylase (13.5%), phosphofructokinase (16.6%), pyruvate kinase (PK, 14.1%) and lactate dehydrogenase (10.7%). Repetition-dependent reductions (P < 0.05) in V(max) were observed for CS (R1, R2 > R16), COX (R1, R2 > R16), Hex (1R, 2R > R16), and PK (R9 > R16). It is concluded that heavy exercise results in transient reductions in a wide range of enzymes involved in different metabolic functions and that in the case of selected enzymes, multiple repetitions of the exercise reduce average V(max).
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PMID:Acute responses in muscle mitochondrial and cytosolic enzyme activities during heavy intermittent exercise. 1820 65

Sodium pyruvate can increase mitochondrial biogenesis in C2C12 myoblasts in a peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC1alpha)-independent manner. The present study examined the effect of 72-h treatment with sodium pyruvate (5-50 mM) or sodium chloride (50 mM) as an osmotic control on the regulation of mitochondrial substrate metabolism and biogenesis in C2C12 myotubes. Pyruvate (50 mM) increased the levels of fatty acid oxidation enzymes (CD36, 61%, and beta-oxidative enzyme 3-hydroxyacyl-CoA dehydrogenase, 54%) and the expression of cytochrome-c oxidase subunit I (220%) and cytochrome c (228%), consistent with its previous described role as a promoter of mitochondrial biogenesis. However, in contrast, pyruvate treatment reduced glucose transporter 4 (42%), phosphofructokinase (57%), and PGC1alpha (72%) protein content as well as PGC1alpha (48%) and PGC1beta (122%) mRNA. The decrease in PGC1alpha was compensated for by an increase in the PGC1alpha-related coactivator (PRC; 187%). Pyruvate treatment reduced basal and insulin-stimulated glucose uptake (41% and 31%, respectively) and palmitate uptake and oxidation (24% and 31%, respectively). The addition of the pyruvate dehydrogenase activator dichloroacetate (DCA) and the TCA precursor glutamine increased PGC1alpha expression (368%) and returned PRC expression to basal. Glucose uptake increased by 4.2-fold with DCA and glutamine and palmitate uptake increased by 18%. Coupled to this adaptation was an 80% increase in oxygen consumption. The data suggest that supraphysiological doses of pyruvate decrease mitochondrial function despite limited biogenesis and that anaplerotic agents can reverse this effect.
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PMID:Pyruvate suppresses PGC1alpha expression and substrate utilization despite increased respiratory chain content in C2C12 myotubes. 2041 Apr 36


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