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:1.6.99.3 (diaphorase)
5,903 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The presence of cholinesterase activity in M. demissus hearts was demonstrated by light- and electron-microscopic histochemistry and by enzymic assay. The enzyme proved to be acetylcholinesterase (AChE) since acetylthiocholine was the preferred substrate, and eserine or BW284C5I inhibited the enzyme activity, while isoOMPA was without effect. The AChE was localized and uniformly distributed along the cell surface membranes of the cardiac muscle cells. A fraction 8-fold enriched in AChE was isolated from pooled ventricles by a combination of differential and sucrose density gradient centrifugation. This sarcolemmal fraction contained little mitochondrial contamination as determined by electron microscopy and by succinate cytochrome c reductase activity. In addition, this fraction stained uniformly for AChE, indicating that it was free of other membrane types (for example sarcoplasmic reticulum which did not stain for AChE). Therefore, this fraction contained purified cell surface membrane free of contamination by other membranous organelles.
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PMID:Acetylcholinesterase: a useful marker for the isolation of sarcolemma from the bivalve (Modiolus demissus demissus) myocardium. 74 38

We report the morphological, biochemical, immunological, and genetic findings in a patient with the clinical characteristics of Leigh's disease due to multisystemic cytochrome c oxidase (CCO) deficiency. Muscle biopsy at 2 years and 5 months of age showed markedly decreased CCO and cytochrome a + a3, moderately decreased NADH-cytochrome c reductase to 46.3%, and generalized loss of immunologically detectable CCO subunits, but other respiratory chain enzyme proteins were normal. All the tissues examined at autopsy showed decreased activity of all respiratory chain enzymes except complex II. The decrease in cytochromes b and a + a3 were in harmony with decreased enzyme activities in complex III and IV (CCO), respectively. All immunologically detectable subunits of CCO in immunoprecipitation were uniformly decreased in the cardiac and skeletal muscles, but subunits 1 and 4 were selectively decreased in other organs except liver. No large deletion could be detected in the cardiac muscle mtDNA after digestion with restriction enzymes. These results suggest that the respiratory chain enzymes are variable in their activity and the amount of enzyme proteins decreases as the disease progresses.
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PMID:Progressive cytochrome c oxidase deficiency in a case of Leigh's encephalomyelopathy. 215 85

Although acetylcholine is known to be involved in the genesis of skeletal muscle disturbance, its effect on cardiac muscle has been scarcely studied. In the present paper, using pyridostigmine, a cholinesterase inhibitor, the possible role of acetylcholine in the genesis of cardiomyopathy was investigated. In a mortality study, it was shown that pyridostigmine (100 mg/kg) caused death of 9/10 rats within 8 h, and that the lethality of such a dose could be significantly diminished by the subsequent administration of a total dose of 4 mg/kg atropine. In all other experiments, rats were divided into three groups; the control, untreated group; the pyridostigmine + atropine group in which atropine (2 mg/kg) was administered 5 min after pyridostigmine (60 mg/kg) administration; and the pyridostigmine group in which pyridostigmine (60 mg/kg) was administered orally. Rats were killed 3 h after pyridostigmine administration, and hearts were isolated. Heart mitochondrial electron transport activity (NADH-cytochrome c reductase, succinate-cytochrome c reductase, and cytochrome c oxidase) were measured enzymatically, and mitochondrial respiratory rates and control indices were measured polarographically. Structural changes in cardiac muscles of each group were observed by electron microscopy of cardiac sections. Acetylcholine levels of left ventricle were measured by high performance liquid chromatography. Activities of NADH-cytochrome c reductase and succinate-cytochrome c reductase were not affected by pyridostigmine administration; however, cytochrome c oxidase activity was significantly reduced in the pyridostigmine group. Atropine markedly lessened this reduction in activity. A protective effect of atropine was also observed morphologically. A protective effect of atropine was also observed morphologically. In the pyridostigmine group and the pyridostigmine + atropine group, left ventricular acetylcholine levels were increased significantly compared with the control.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of acetylcholine in pyridostigmine-induced myocardial injury: possible involvement of parasympathetic nervous system in the genesis of cardiomyopathy. 273 Mar 38

The effects of iron deficiency in rat and/or man on iron-containing enzymes of different tissues is reviewed. Iron deficiency results in a decrease of skeletal muscle iron containing proteins e.g. myoglobin, cytochromes c, a + a3, and alpha-glycerophosphate oxidase. Iron deficiency produces a reduction in the activity of several respiratory enzymes in the mitochondrial fraction of cardiac muscle, particularly: NADH cytochrome c reductase, succinic cytochrome c reductase, succinic dehydrogenase and NADH ferricyanide oxidoreductase. The effects of iron deficiency on brain tissue is emphasized with respect to cytochromes, monoaminoxidase and amino acids metabolism. Host defence to infection (controversial data), decrease in body temperature, alteration of DNA synthesis, collagen and lipid metabolism, liver and gastrointestinal mucous cytochromes activity perturbations are discussed.
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PMID:The activity of tissue enzymes in iron-deficient rat and man: an overview. 637 45

The effects of BRB-I-28 and its derivatives (GLG-V-13, SAZ-VII-22 and SAZ-VII-23), a novel group of antiarrhythmic agents, were investigated on the rat heart mitochondrial respiratory chain. The results indicate that BRB-I-28 and its derivatives have concentration-dependent inhibitory effects on NADH oxidase and NADH-CoQ reductase (complex I), but they have no significant effects on succinate oxidase, succinate dehydrogenase (complex II), CoQ-cytochrome c reductase (complex III), cytochrome c oxidase (complex IV), and NADH-K3Fe(CN)6 reductase. The site of inhibition of BRB-I-28 and its derivatives on the respiratory chain was localized between flavoprotein n (FPn) and CoQ, which is similar to the effect of rotenone and several other antiarrhythmic drugs such as amiodarone, propranolol, etc. BRB-I-28 and its derivatives also have significant inhibitory effects on mitochondrial ATPase activity as reported for other antiarrhythmic drugs such as amiodarone, propranolol, quinidine, and lidocaine. However, BRB-I-28 and its derivatives have no direct effects on sarcoplasmic reticulum Ca(2+)-ATPase activity. The inhibitory effects of BRB-I-28 and its derivatives on mitochondrial oxidative phosphorylation may result in the depletion of ATP. This effect, in combination with their effects on Na+,K(+)-ATPase, could possibly produce an increase in Ca2+ concentration in cytosol. This may be another mechanism by which these DHBCN derivatives produce an increase in systemic arterial blood pressure and contractile force of isolated cardiac muscle. On the other hand, inhibition on mitochondrial respiration may account for some of the potential toxic effects of these diheterabicyclo[3.3.1]nonane derivatives.
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PMID:Effects of novel antiarrhythmic agents, BRB-I-28 and its derivatives, on the heart mitochondrial respiratory chain and sarcoplasmic reticulum Ca(2+)-ATPase. 799 64

The metabolic changes in the homografted canine heart were studied in order to define the biochemical alterations accompanying homograft rejection. In several experiments, homograft rejection was accelerated by prior sensitization of the host animal. The homografted heart released pyruvate and lactate as well as malic dehydrogenase and aldolase. Extraction of glucose by the graft usually remained positive. During the accelerated rejection, the release of pyruvate and lactate was more pronounced, and even glucose appeared in increased concentrations in coronary vein blood. In many experiments the respiratory quotient of the transplanted heart as well as its glucose-oxygen extraction ratio were elevated. It seemed likely that the elevated respiratory quotients were the result of conversion of carbohydrates to fat, since the injection of thiamine hydrochloride resulted in further elevation of the respiratory quotient and in an increased myocardial pyruvate extraction. Apparently, thiamine corrected a metabolic block at the level of the cocarboxylase. The metabolic block or blocks present in the transplanted heart are likely to be the result of diminution in intracellular enzymes and coenzymes resulting from increased cellular permeability. The redox potential across the transplanted heart was positive, indicating the absence of anoxia. The results illustrate that glycolysis proceeds in the transplanted heart in the presence of oxygen. Histopathologic and histochemical studies show the earliest lesion to be an accumulation of lymphocytes around vessels at 3 hours. Swelling of vascular endothelium occurs. By 5 hours a polar perivascular cellular infiltrate of lymphocytes, plasma cells, macrophages, and histiocytes exists. Changes following at 19 hours show the appearance of Aschoff- and Anitschkow-like cells. Granulomatous myocarditis which was first perivascular became interstitial with lymphocytic and histiocytic invasion of the myocardium. After 8 days acceleration of swelling of vascular endothelium and granulomatous lesions were observed and necrosis of the myocardium was prominent. Endothelial hyperplasia occurred at 14 days. In the accelerated reaction these changes were intensified and necrosis began as early as 4 hours after grafting. Histochemical changes of DPNH diaphorase, lactic, malic, and succinic dehydrogenase showed only significant diminution of malic dehydrogenase in the cardiac muscle which was concurrent with the increase of this enzyme in the serum.
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PMID:Studies on the transplanted heart. Its metabolism and histology. 1387 18

Dilated cardiomyopathy (DCM) is widely accepted as a pluricausal or multifactorial disease. Because of the linkage between energy metabolism in the mitochondria and cardiac muscle contraction, it is reasonable to assume that mitochondrial abnormalities may be responsible for some forms of DCM. We analysed the whole mitochondrial genome in a series of 45 patients with DCM for alterations and compared the findings with those of 62 control subjects. A total of 458 sequence changes could be identified. These sequence changes were distributed among the whole mitochondrial DNA (mtDNA). An increased number of novel missense mutations could be detected nearly in all genes encoding for protein subunits in DCM patients. In genes coding for NADH dehydrogenase subunits the number of mtDNA mutations detected in patients with DCM was significantly increased (p < 0.05) compared with control subjects. Eight mutations were found to occur in conserved amino acids in the above species. The c.5973G > A (Ala-Trp) and the c.7042T > G (Val-Asp) mutations were located in highly conserved domains of the gene coding for cytochrome c oxidase subunit. Two tRNA mutations could be detected in the mtDNA of DCM patients alone. The T-C transition at nt 15,924 is connected with respiratory enzyme deficiency, mitochondrial myopathy, and cardiomyopathy. The c.16189T > C mutation in the D-loop region that is associated with susceptibility to DCM could be detected in 15.6% of patients as well as in 9.7% of controls. Thus, mutations altering the function of the enzyme subunits of the respiratory chain can be relevant for the pathogenesis of dilated cardiomyopathy.
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PMID:Novel point mutations in the mitochondrial DNA detected in patients with dilated cardiomyopathy by screening the whole mitochondrial genome. 1512 Jun 34

Cardiolipin (CL) is a mitochondrial phospholipid essential for electron transport chain (ETC) integrity. CL-deficiency in humans is caused by mutations in the tafazzin (Taz) gene and results in a multisystem pediatric disorder, Barth syndrome (BTHS). It has been reported that tafazzin deficiency destabilizes mitochondrial respiratory chain complexes and affects supercomplex assembly. The aim of this study was to investigate the impact of Taz-knockdown on the mitochondrial proteomic landscape and metabolic processes, such as stability of respiratory chain supercomplexes and their interactions with fatty acid oxidation enzymes in cardiac muscle. Proteomic analysis demonstrated reduction of several polypeptides of the mitochondrial respiratory chain, including Rieske and cytochrome c1 subunits of complex III, NADH dehydrogenase alpha subunit 5 of complex I and the catalytic core-forming subunit of F0F1-ATP synthase. Taz gene knockdown resulted in upregulation of enzymes of folate and amino acid metabolic pathways in heart mitochondria, demonstrating that Taz-deficiency causes substantive metabolic remodeling in cardiac muscle. Mitochondrial respiratory chain supercomplexes are destabilized in CL-depleted mitochondria from Taz knockdown hearts resulting in disruption of the interactions between ETC and the fatty acid oxidation enzymes, very long-chain acyl-CoA dehydrogenase and long-chain 3-hydroxyacyl-CoA dehydrogenase, potentially affecting the metabolic channeling of reducing equivalents between these two metabolic pathways. Mitochondria-bound myoglobin was significantly reduced in Taz-knockdown hearts, potentially disrupting intracellular oxygen delivery to the oxidative phosphorylation system. Our results identify the critical pathways affected by the Taz-deficiency in mitochondria and establish a future framework for development of therapeutic options for BTHS.
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PMID:Cardiac metabolic pathways affected in the mouse model of barth syndrome. 2603 Apr 9

The aim of this study was to identify novel long non-coding RNA (lncRNA) biomarkers associated with dilated cardiomyopathy (DCM) and reveal the potential molecular mechanisms of DCM development using bioinformatics approaches. The array data of GSE5406, including 108 DCM samples and 16 non-failing control samples, were obtained from the Gene Expression Omnibus database. The differentially expressed lncRNAs were identified using limma package in R. Pearson's correlation analyses were performed between the differentially expressed lncRNAs and protein-coding genes based on their expression levels. Pathway enrichment of these lncRNAs was conducted based on the significantly co-expressed genes. From the receiver operating characteristic (ROC) curve, the area under the ROC curve (AUC) value was obtained and used for evaluating discriminatory ability. IDI2-AS1 and XIST were differentially expressed in DCM patients. A total of 510 co-expressed genes were identified. The enriched functions and pathways of the co-expressed genes mainly included NADH dehydrogenase activity, cardiac muscle contraction, and oxidative phosphorylation. The ROC curve analysis indicated that the two lncRNAs have favorable diagnostic values in DCM. The AUC values of XIST, IDI2-AS1, and the combination of XIST and IDI2-AS1 were 0.733 (95% CI: 0.646-0.809), 0.796 (95% CI: 0.715-0.863), and 0.823 (95% CI: 0.745-0.886), respectively. This study identified IDI2-AS1 and XIST lncRNAs and related pathways involved in the pathogenesis of DCM, thus providing potential diagnostic and therapeutic targets for DCM.
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PMID:Identification of differentially expressed long non-coding RNAs associated with dilated cardiomyopathy using integrated bioinformatics approaches. 3272 80

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