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:1.3.5.1 (succinate dehydrogenase)
8,177 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Renal clear cell tubules and clear/acidophilic cell tumors were induced in male Sprague-Dawley rats by 7 weeks oral administration (stop model) of N-nitrosomorpholine (NNM) at a concentration of 12 mg/100 ml in the drinking water. Twelve, 23 and 34 weeks after withdrawal of NNM serial cryostat sections of the kidneys were histochemically analyzed for the following parameters: glucose transporter proteins (GLUT1, GLUT2), glycogen content and the activities of glycogen synthase (SYN), glycogen phosphorylase (PHO), glucose-6-phosphatase (G6Pase), glucose-6-phosphate dehydrogenase (G6PDH), hexokinase (HK), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), pyruvate kinase (PK), succinate dehydrogenase (SDH), malate dehydrogenase (MDH), alkaline phosphatase (ALP), acid phosphatase (ACP) and gamma-glutamyltransferase (GGT). Clear cell (glycogenotic) tubules first appeared at 23 weeks, and clear/acidophilic cell tumors at 34 weeks after withdrawal of the carcinogen. G6Pase, ALP, GGT and GLUT2 were absent in clear cell tubules, clear/acidophilic cell tubules, and clear/acidophilic cell tumors indicating a sequential origin of all these types of lesions from the collecting duct system, in line with previous morphological findings. In comparison to the collecting duct epithelium, glycogenotic tubules demonstrated an increased activity of PHO and reduced activities of glycolytic and mitochondrial enzymes, which were accompanied by a strongly reduced expression of GLUT1. Moderately increased activities of glycolytic and mitochondrial enzymes were observed in the clear cells of clear/acidophilic cell tubules and tumors compared with those in glycogenotic tubules. They had slightly increased activities of the glycolytic enzymes GAPDH and PK compared with normal collecting duct epithelium, while most of them were nearly lacking in GLUT1. Our findings suggest that glycogen storage is not due to an increased uptake of glucose from the blood, but results from a disturbance in intracellular flux of metabolites. The development of clear cell tubules from the normal collecting duct epithelium is accompanied by a markedly decreased expression of GLUT1 along with a reduction in glycolytic and mitochondrial enzymes. This reduction of enzyme activities is replaced by an increase in enzyme activities in clear/acidophilic cell tumors indicating a fundamental shift in carbohydrate metabolism during progression from preneoplastic to neoplastic lesions.
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PMID:Sequential changes in glycogen content, expression of glucose transporters and enzymic patterns during development of clear/acidophilic cell tumors in rat kidney. 147 41

The effects of long-term, moderate physical exercise on in vivo glucose uptake, levels of two glucose transporter proteins (GLUT1 and GLUT4) and activities of various key enzymes of energy metabolism were measured in skeletal muscle from streptozotocin-diabetic rats. Diabetes (12-16 weeks) reduced the in vivo glucose uptake (glucose metabolic index, GMI) in muscle containing mainly type I fibres by 55% but had no effect in muscles containing mainly type IIa and IIb fibres. GMI was increased in the diabetic white skeletal muscle (mainly type IIb fibres) by more than 120%. In contrast to the complex changes in GMI, GLUT4 levels were reduced in all types of skeletal muscle from diabetic rats with no change in GLUT1 levels. Exercise training had no effects on GMI or the glucose transporter levels. Streptozotocin induced diabetes significantly reduced the oxidative capacity of skeletal muscle assayed as the activities of citrate synthase, succinate dehydrogenase and cytochrome c oxidase. Training increased the activities of oxidative enzymes, with this increase being more prominent in the diabetic animals. The present data indicate that long-term streptozotocin-induced diabetes decreases oxidative metabolic capacity and GLUT4 protein levels in skeletal muscle, but that the changes of glucose transport largely depend on the fibre type composition. Moderate training fully reverses the effect of insulinopenia and hyperglycaemia on muscle oxidative metabolism. In contrast to the previous suggestions, the expression of GLUT4 is not correlated with the capacity of oxidative metabolism in skeletal muscle of streptozotocin-diabetic rats.
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PMID:Dissociation of the effects of training on oxidative metabolism, glucose utilisation and GLUT4 levels in skeletal muscle of streptozotocin-diabetic rats. 797 Nov 42

The Escherichia coli sdhCDAB operon encodes succinate dehydrogenase, an enzyme complex involved in the tricarboxylic acid (TCA) cycle. Expression of this operon is under complex transcriptional regulation in response to growth conditions, such as anaerobiosis and carbon sources. Typically, the expression of sdhCDAB is known to be subjected to "an aerobic repression" and "a glucose repression." The molecular mechanism underlying the anaerobic repression has been well documented, involving both the ArcB-ArcA two-component system and the Fnr global anaerobic regulator. However, the mechanism underlying the glucose repression is not yet clear, because the involvement of the general catabolite regulators such as CRP and CRA has been dismissed. In this study, we conducted a series of genetic analyses to identify the regulator gene(s) involved in the glucose repression of sdh. The results demonstrate that the EIICB(Glc) protein (the ptsG gene product), a component of the major glucose transporter, acts as a crucial mediator in glucose repression. These results support the view that the EIICB(Glc) protein functions not only as a glucose transporter, but also as a glucose-sensing signal transducer that modulates the glucose repression of the sdhCDAB operon.
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PMID:Repression of the gene encoding succinate dehydrogenase in response to glucose is mediated by the EIICB(Glc) protein in Escherichia coli. 1042 29

In the present study, differences in glucose uptake by muscle fibers in deep, middle, and superficial regions of the gastrocnemius were studied at rest by 2-deoxyglucose (2-DG) microautoradiography. Expression of the glucose transporter 4 (GLUT-4) protein, an isoform of the glucose transporter family, was analyzed as well. These data were compared with the activity of succinate dehydrogenase, a marker of oxidative metabolism, a-glycerophosphate dehydrogenase, an indicator of the glycolytic capacity, and myofibrillar ATPase. In the deep regions of the muscle, most fibers (86.9%) showed high 2-DG uptake and large amounts of GLUT-4 protein, whereas in the superficial regions, all fibers showed low 2-DG uptake and GLUT-4 expression. In the middle regions, fibers dominated (80.4%) showed low 2-DG uptake and small amounts of GLUT-4 protein. Analysis of metabolic properties revealed that most fibers in the deep region were oxidative and showed the highest 2-DG uptake; in the superficial region, the fibers were anaerobic and showed the lowest 2-DG uptake. In the middle region, most fibers were of the anaerobic and fast twitch type. It is concluded that 2-DG uptake correlates with GLUT-4 expression in the plasma membrane of type I and IIx fibers rather than with oxidative enzyme activity.
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PMID:Microautoradiographic studies of glucose uptake in skeletal muscle fibers at rest. 1170 Sep 42

To gain better insight into the insulin secretory activity of fetal beta cells in response to glucose, the expression of glucose transporter 2 (GLUT-2), glucokinase and mitochondrial glycerol phosphate dehydrogenase (mGDH) were studied. Expression of GLUT-2 mRNA and protein in pancreatic islets and liver was significantly lower in fetal and suckling rats than in adult rats. The glucokinase content of fetal islets was significantly higher than of suckling and adult rats, and in liver the enzyme appeared for the first time on about day 20 of extrauterine life. The highest content of hexokinase I was found in fetal islets, after which it decreased progressively to the adult values. Glucokinase mRNA was abundantly expressed in the islets of all the experimental groups, whereas in liver it was only present in adults and 20-day-old suckling rats. In fetal islets, GLUT-2 and glucokinase protein and their mRNA increased as a function of increasing glucose concentration, whereas reduced mitochondrial citrate synthase, succinate dehydrogenase and cytochrome c oxidase activities and mGDH expression were observed. These findings, together with those reported by others, may help to explain the decreased insulin secretory activity of fetal beta cells in response to glucose.
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PMID:Expression of glucose transporter-2, glucokinase and mitochondrial glycerolphosphate dehydrogenase in pancreatic islets during rat ontogenesis. 1178 5

Intracerebral C6 glioma xenografts spontaneously develop centrally located necrotic regions that are bordered by densely packed neoplastic cells. Proliferative and metabolic heterogeneity in these perinecrotic regions were assessed by bromodeoxyuridine (BrdU) incorporation, by immunocytological and by histochemical analyses. The borders of necrotic regions are comprised of glioma cells that express increased levels of the type 1 glucose transporter (GLUT-1) with rare cells having incorporated BrdU. By contrast, BrdU-positive glioma cells are located immediately adjacent to GLUT-1-positive cells bordering areas of necrosis. BrdU-positive glioma cells are also scattered throughout poorly vascularized, central regions of the tumor and are present at the highly vascularized tumor periphery. GLUT-1 expression increased considerably when C6 glioma cells were grown for 48 h under either the acidotic conditions of pH 6.8 or under hypoxic conditions. The perinecrotic GLUT-1-positive glioma cells in poorly vascularized, centrally located tumor regions demonstrated a 75% reduction in glycogen content and negligible glycogenolytic capacity, when compared with normal brain white matter. Cytochrome c oxidase (COX) and lactate dehydrogenase (LDH) maintained 50% enzymatic activity compared to controls, while succinate dehydrogenase (SDH) activity was 25% of control values. Based upon these findings, a metabolic model is proposed in which GLUT-1-positive perinecrotic cells are growth arrested and predominantly rely upon non-oxidative glycolysis. It is further postulated that BrdU-positive, GLUT-1-negative glioma cells within the poorly vascularized, central tumor region convert glucose-6-phosphate to nucleotide precursors for DNA replication.
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PMID:Perinecrotic glioma proliferation and metabolic profile within an intracerebral tumor xenograft. 1471

The objective of this paper is to provide an overview of the recent developments in muscle physiology and biochemistry in general, and with respect to chronic obstructive pulmonary disease (COPD) specifically. As a way of illustration, we have presented data on the remodeling that occurs in vastus lateralis in two patients with COPD (COPD #1, forced expiratory volume in one second/forced vital capacity [FEV(1)/FVC] = 63%; COPD #2, FEV(1)/FVC = 41%) exhibiting differences in muscle wasting as compared to healthy controls (CON; FEV(1)/FVC = 111 +/- 2.2%, n = 4). Type I fibers percentages were lower in both COPD #1 (16.7) and COPD #2 (24.9) compared to CON (57.3 +/- 5.2). Cross sectional area of the type I fibers of the patients ranged between 65%-68% of CON and for the type II subtypes (IIA, IIAX, IIX) between 74% and 89% (COPD #1) and 17%-32% (COPD #2). A lower number of capillary contacts were observed for all fiber types in COPD #1 but not COPD #2. Lower concentrations of adenosine triphosphate (ATP) (24%-26%) and phosphocreatine (18%-20%), but not lactate occurred in COPD. In contrast to COPD #1, who displayed normal glucose transporter content, GLUT1 and GLUT4 were only 71% and 54%, respectively of CON in COPD #2. Lower monocarboxylate contents were found for MCT1 in both COPD #1 (63%) and COPD #2 (41%) and for MCT4 (78%) in COPD #1. Maximal oxidative enzyme activities (V(max)) for COPD #2 ranged between 37% (succinic dehydrogenase) and 70% (cytochrome C oxidase) of CON. For the cytosolic enzymes, V(max) ranged between 89% (hexokinase) to 31% (pyruvate kinase) of CON. Depressions were also observed in V(max) of the Na(+)-K(+)-ATPase for COPD #1 (66% of CON) but not COPD #2 (92% of CON) while V(max) of the Ca(2+)-ATPase was near normal in COPD #1 (84% CON). It is concluded that disturbances can occur in muscle to a wide range of excitation, contraction and metabolic processes in COPD.
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PMID:Cellular assessment of muscle in COPD: case studies of two males. 2036 Sep 8

The yeast protein kinases Sat4/Hal4 and Hal5 are required for the plasma membrane stability of the K(+) transporter Trk1 and some amino acid and glucose permeases. The transcriptomic analysis presented here indicates alterations in the general control of the metabolism of both nitrogen and carbon. Accordingly, we observed reduced uptake of methionine and leucine in the hal4 hal5 mutant. This decrease correlates with activation of the Gcn2-Gcn4 pathway, as measured by expression of the lacZ gene under the control of the GCN4 promoter. However, with the exception of methionine biosynthetic genes, few amino acid biosynthetic genes are induced in the hal4 hal5 mutant, whereas several genes involved in amino acid catabolism are repressed. Concerning glucose metabolism, we found that this mutant exhibits derepression of respiratory genes in the presence of glucose, leading to an increased activity of mitochondrial enzymes, as measured by succinate dehydrogenase (SDH) activity. In addition, the reduced glucose consumption in the hal4 hal5 mutant correlates with a more acidic intracellular pH and with low activity of the plasma membrane H(+)-ATPase. As a compensatory mechanism for the low glycolytic rate, the hal4 hal5 mutant overexpresses the HXT4 high-affinity glucose transporter and the hexokinase genes. These results indicate that the hal4 hal5 mutant presents defects in the general control of nitrogen and carbon metabolism, which correlate with reduced transport of amino acids and glucose, respectively. A more acidic intracellular pH may contribute to some defects of this mutant.
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PMID:Hal4 and Hal5 protein kinases are required for general control of carbon and nitrogen uptake and metabolism. 2095 80

A glycolytic profile unifies a group of pheochromocytomas and paragangliomas (PHEOs/PGLs) with distinct underlying gene defects, including von Hippel-Lindau (VHL) and succinate dehydrogenase B (SDHB) mutations. Nevertheless, their tumor aggressiveness is distinct: PHEOs/PGLs metastasize rarely in VHL-, but frequently in SDHB-patients. To date, the molecular mechanisms causing the more aggressive phenotype in SDHB-PHEOs/PGLs remain largely unknown. Recently, however, an excellent model to study aggressive PHEOs (mouse tumor tissue (MTT) cells) has been developed from mouse PHEO cells (MPC). We employed this model for a proteomics based approach to identify changes characteristic for tumor aggressiveness, which we then explored in a homogeneous set of human SDHB- and VHL-PHEOs/PGLs. The increase of glucose transporter 1 in VHL, and of hexokinase 2 in VHL and SDHB, confirmed their glycolytic profile. In agreement with the cell model and in support of decoupling of glycolysis, the Krebs cycle and oxidative phosphorylation (OXPHOS), SDHB tumors showed increased lactate dehydrogenase levels. In SDHB-PGLs OXPHOS complex activity was increased at complex III and, as expected, decreased at complex II. Moreover, protein and mRNA expression of all tested OXPHOS-related genes were higher in SDHB- than in VHL-derived tumors. Although there was no direct evidence for increased reactive oxygen species production, elevated superoxide dismutase 2 expression may reflect elevated oxidative stress in SDHB-derived PHEOs/PGLs. For the first time, we show that despite dysfunction in complex II and evidence for a glycolytic phenotype, the Warburg effect does not seem to fully apply to SDHB-PHEOs/PGLs with respect to decreased OXPHOS. In addition, we present evidence for increased LDHA and SOD2 expression in SDHB-PHEOs/PGLs, proteins that have been proposed as promising therapeutic targets in other cancers. This study provides new insight into pathogenic mechanisms in aggressive human PHEOs/PGLs, which may lead to identifying new diagnostic and prognostic markers in the near future.
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PMID:Warburg effect's manifestation in aggressive pheochromocytomas and paragangliomas: insights from a mouse cell model applied to human tumor tissue. 2285 59

Exercise training induces muscular adaptations that are highly specific to the type of exercise. For a systematic study of the differentiated exercise adaptations on a molecular level mouse models have been used successfully. The aim of the current study was to develop a suitable mouse model of isometric strength exercise training characterized by specific adaptations known from strength training. C57BL/6 mice performed an isometric strength training (ST) for 10 weeks 5 days/week. Additionally, either a sedentary control group (CT) or a regular endurance training group (ET) groups were used as controls. Performance capacity was determined by maximum holding time (MHT) and treadmill spirometry, respectively. Furthermore, muscle fiber types and diameter, muscular concentration of phosphofructokinase 1 (PFK), succinate dehydrogenase (SDHa), and glucose transporter type 4 (GLUT4) were determined. In a further approach, the effect of ST on glucose intolerance was tested in diabetic mice. In mice of the ST group we observed an increase of MHT in isometric strength tests, a type II fiber hypertrophy, and an increased GLUT4 protein content in the membrane fraction. In contrast, in mice of the ET group an increase of VO(2max), a shift to oxidative muscle fiber type and an increase of oxidative enzyme content was measured. Furthermore strength training was effective in reducing glucose intolerance in mice fed a high fat diet. An effective murine strength training model was developed and evaluated, which revealed marked differences in adaptations known from endurance training. This approach seems also suitable to test for therapeutical effects of strength training.
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PMID:Functional and muscular adaptations in an experimental model for isometric strength training in mice. 2423 89


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