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)

A 5-month-old boy died of progressive heart failure that started at the age of 3 months. Autopsy revealed a mitochondrial cardiomyopathy and a mitochondrial myopathy of the limb muscle and diaphragm. Cytochemically random defects of cytochrome c oxidase were visualized by light and electron microscopy in the diaphragm and especially the heart muscle, the limb muscle showing a diffuse attenuation whereas the liver and kidneys reacted normally. The activities of NADH-dehydrogenase (complex I) and cytochrome c oxidase (complex IV) were severely diminished (20% residual activity of controls) in the skeletal and heart muscle. In the heart, succinate cytochrome c reductase (complex II/III) was additionally decreased to the same degree. Loss of cytochrome c oxidase activity was based on a reduction of both mitochondrial and nuclear derived subunits in the heart and diaphragm as revealed by immunohistochemical analysis, whereas the limb muscle showed a normal immunoreactive protein content. The results illustrate heterogeneous tissue expression of respiratory chain enzyme defects and demonstrate that a cardiomyopathy may be the leading presentation of a mitochondrial disorder in early infancy.
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PMID:Fatal infantile mitochondrial cardiomyopathy and myopathy with heterogeneous tissue expression of combined respiratory chain deficiencies. 165 34

An experimental model of myocardiopathy was induced in rhesus monkeys following noradrenaline (NA) infusion (20 ug/kg body wt/minute), for a period of 2 hours daily for three consecutive days. The animals were sacrificed after two hours (acute phase), forty-eight hours (sub-acute phase) and twenty-one days (chronic phase). Focal depletion of succinic dehydrogenase, increase in adenosine triphosphatase, acid phosphatase and appearance of large fat droplets in myocardial muscle was noted in the acute phase. Histopathological examination revealed focal edema, opacity and fuchsinorrhagia of the muscle fibres distributed in both the ventricles. Myofibrillar degeneration, myocytolysis and vacuolization with aggregation of lymphomononuclear cells were the significant features in the acute phase. During sub-acute and chronic phases, these features became less prominent and reparative changes with proliferation of fibroblasts became more marked. By the twenty-first day, irregular, focal scars replaced the necrosed myocardium. Ultrastructurally, heart muscle showed myofibrillar disorganisation, distortion of Z and A bands, dilatation of sarcoplasmic reticulum and swelling and rupture of mitochondria. Altered membrane permeability was evidenced by the presence of reaction products of horseradish peroxidase within the cardiac cells. In the reparative phase, however, myocytolytic changes regressed and collagen deposition was the prominent feature. This experimental study has several histological features simulating human cases of myocardial infarction without coronary occlusion.
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PMID:Catecholamine-induced experimental cardiomyopathy--a histopathological, histochemical and ultrastructural study. 259 40

Keshan disease (KD) is a cardiomyopathy endemic in certain areas of China, characterized by severe deterioration and multiple focal necrosis. In the present paper we describe abnormalities of the structure and function of myocardial mitochondria from patients with subacute Keshan disease. Activities of succinate dehydrogenase, succinic oxidase, cytochrome c oxidase, H(+)-ATPase and its sensitivity to oligomycin and the response of membrane potential to energization by ATP were significantly decreased. However, the spectrum of reduced-minus-oxidized cytochromes in patients' mitochondria showed no obvious difference in the content of cytochrome c oxidase (aa3). There was also a marked decrease in lipid fluidity of affected mitochondria, and an abnormal amount of moderately electron dense amorphous inclusions. Electron-microscopic x-ray microanalysis and exposure to protein digestion reagent demonstrated that these inclusions are not Ca3(PO4)2, but are, probably, proteinaceous in nature. Affected mitochondria had markedly decreased selenium content. The defects in myocardial mitochondria from patients with chronic Keshan disease were less extensive than those in patients with subacute Keshan disease. We propose that Keshan disease be classified as a form of "mitochondrial cardiomyopathy".
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PMID:Keshan disease--an endemic mitochondrial cardiomyopathy in China. 290 94

Biochemical investigations were performed on cardiac muscle samples from seven dogs with cardiomyopathy and on cardiac muscle from a varied selection of normal dogs. Biochemical examination of cardiac muscle from clinical cases of cardiomyopathy revealed that the concentrations of three enzymes were significantly altered. These were, catalase, succinic dehydrogenase and malate dehydrogenase. Depressed enzyme concentrations were recorded from both ventricles but were significant only on the left for catalase, on the right for malate dehydrogenase and in both ventricles for succinic dehydrogenase although the depression in this case was also greater on the right.
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PMID:Biochemical investigations of cardiomyopathy in the dog. 362 75

Defects of the mitochondrial respiratory chain in cardiac muscle are an important, yet still overlooked cause of heart failure. In 16 of 32 endocardial biopsies from infants affected by "idiopathic" hypertrophic cardiomyopathy we demonstrated a remarkable decrease of activity of either complex I, or complex IV, or both, relative to complex II + III activity which was taken as an index of mitochondrial proliferation. At the molecular level, several mtDNA mutations have been associated with cardiomyopathy. For instance, MIMyCa is a maternally inherited syndrome presenting with a variable combination of skeletal and heart muscle failure associated with a heteroplasmic A3260G transition in the tRNALeu(UUR) gene. To study the effects of the mutation in a controlled system, we prepared clones of transmitochondrial cybrids by fusing mutant cytoplasts with mtDNA-less tumor cells. Two groups of clones were identified: nearly 100% mutant (M group) and nearly 100% wild-type (WT group). The means of complex I and IV in the M group were 63% and 67% relative to the WT group. The O2 consumption in the M group was 36%, and the lactate production was 218% of that in the WT group. MtDNA-specific translation was defective in M clones. The study of transmitochondrial cybrids is an important clue to test the pathogenicity of mtDNA mutations.
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PMID:OXPHOS defects and mitochondrial DNA mutations in cardiomyopathy. 760 20

The results of laboratory investigations in concerning 15 patients suspected of mitochondrial disease (MD) are presented. Our purpose is to provide an outline of the investigative modalities that support the clinical suspicion and have been found to be useful in the diagnosis. Five clinical groups were studied including 5 exercise intolerances (2 with inflammatory myopathy), 3 with myopathies (1 with dilated cardiomyopathy), 2 with progressive external oftalmoplegia (1 associated with cerebellar ataxia+epilepsy+hypertrophic cardiomyopathy+pes cavus), 4 with encephalopathies (3 with myoclonic encephalopathies with ataxia and dementia and 1 with epilepsy and tremor), and 1 with metabolic acidosis and cardiomyopathy. We used the following categories of investigative procedures: clinical phenotype analysis including pedigree study, neurophysiological tests, bicycle ergometric evaluation, neuroimaging, microscopic study of skeletal muscle biopsy, post-mortem examination, biochemical assays and molecular genetic studies. EMG showed myopathic changes in 5 cases, features of neuropathy in 2, mixed myopathic and neuropathic pattern in 1 and nonspecific changes in 3. EMG was normal in 3 patients. The most common skeletal muscle abnormalities were variation in fiber size (60%), lipid inclusions (33.3%), oxidative subsarcolemmal aggregates (26.7%) and ragged-red fibers (26.7%). Electron microscopy revealed mitochondrial abnormalities in 8 out of 14 patients' muscle biopsies, and in myocardiac and hepatic tissues of another. Site of biochemical defect was located in 12 patients. Complex I defect in 6, complexes I+IV deficiencies in 3, complex II defect in 1, complex IV deficiency in 1, complexes II+IV deficiencies in 1, and complex III defect in 1. In 2 patients the biochemical defect was not located. Mitochondrial DNA alterations were not found in 7 investigated patients. The clinical spectrum of MD has become increasingly wider. After the clinica suspicion, the diagnosis depends up on the appropriate use of skeletal muscle biopsy, biochemical investigations and molecular genetic techniques. Conventional EMG and automatic measurement of the electromyogram are particularly helpful in confirming the clinical suspicion in patients with predominantly central nervous system disease or in cases in which clinical signs are few.
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PMID:[Clinical and investigative approaches in mitochondrial diseases. A review of 15 cases]. 780 49

Diabetes mellitus is often associated with a cardiomyopathy characterized by alterations in cardiac metabolism and declines in cardiac performance. We sought to determine whether exercise training would attenuate the depressed cardiac performance seen in diabetic animals. Female rats were divided into four groups: sedentary control, trained control, sedentary diabetics, and trained diabetics. After 1 week of training, we induced diabetes by intravenous injection of streptozotocin (65 mg/kg). We trained animals on a treadmill using a progressive protocol that plateaued at 27 m/min for 1 hr/day, 5 days/week for a total of 8 weeks. We measured cardiac output at a variety of left atrial filling pressures with an isolated working heart apparatus; glucose was the sole metabolic substrate for the heart. Training increased succinate dehydrogenase activity in the soleus muscle of exercised rats, but did not change heart and body weights or plasma glucose and thyroid hormone levels. The diabetic groups exhibited depressed cardiac outputs at high workloads compared to nondiabetics. Training increased the cardiac output of both sedentary and diabetic animals at high, but not low, preloads. We suggest that exercise can attenuate the severity of diabetic cardiomyopathy.
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PMID:Exercise training improves cardiac performance in diabetic rats. 850 62

We report on 2 children, brother and sister, who presented with cardiomyopathy and muscular hypotonia at the age of B months. They both excreted significant amounts of 3-hydroxy-3-methylglutaric acid (3-HMG) and 3-methylglutaconic acid (3-MGC) but no 3-methylglutaric acid (3-MG). Enzyme analysis in fibroblasts revealed normal activities of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) lyase and of 3-methylglutaconyl hydratase and other enzymes of 3-HMG metabolism. Loading tests with leucine did not affect the excretion of 3-HMG and 3-MGC. The girl died as a result of her cardiomyopathy, while the boy recovered and was treated with cardiac supportive therapy. He showed a steady improvement during his clinical course with biochemical normalization of the urinary excretion of 3-HMG, concomitant with marked improvement in the hypertrophic cardiomyopathy. In cultured fibroblasts from both patients a reduced activity of complex II/III of the respiratory chain was measured which may be the cause of this new type of 3-HMG uria. Analysis of mitochondrial DNA heart muscle, liver and fibroblast culture of the patient did not reveal any major mitochondrial DNA rearrangements (deletion, duplication) or any point mutation that had been described in association with mitochondrial cardiomyopathy.
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PMID:Combined 3-methylglutaconic and 3-hydroxy-3-methylglutaric aciduria with endocardial fibroelastosis and dilatative cardiomyopathy in male and female siblings with partial deficiency of complex II/III in fibroblasts. 925 90

Anti-mitochondrial antibodies (anti-M7) in sera from patients with dilated cardiomyopathy and myocarditis recognize, besides mitochondrial antigens, bacterial sarcosine dehydrogenase. The common target antigen was identified as the covalently bound FAD of mitochondrial and bacterial flavoenzymes. Thus, anti-M7-positive serum reacted on Western blots exclusively with covalently flavinylated enzymes. The antigenic specificity of anti-M7 sera was reproduced by an antiserum raised in rabbits with 6-hydroxy-D-nicotine oxidase. The heart mitochondrial membrane antigen recognized by anti-M7 serum was identified as the flavoprotein subunit of succinate dehydrogenase, the antigens in rat liver mitochondrial matrix as the flavoenzymes dimethylglycine dehydrogenase and sarcosine dehydrogenase. Anti-M7 serum contained a specific anti-flavoenzyme antibody fraction. Nanomolar concentrations of FAD and riboflavin inhibited the immune reaction on Western blots and in ELISA, and incubation with FAD-agarose depleted the anti-M7 activity of the serum. N-terminally deleted dimethylglycine dehydrogenase proteins were only immunoprecipitated by anti-M7 sera when the FAD was covalently incorporated. An affinity constant (KD) of 10(-8) M was established for the anti-flavoenzyme antibodies by competitive ELISA. Of patients with cardiomyopathy and myocarditis, 36% and 25%, respectively, were anti-flavoenzyme-positive by Western blot and ELISA, but only two of 15 patients with other heart diseases and none of 50 healthy controls.
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PMID:Anti-mitochondrial antibodies in patients with dilated cardiomyopathy (anti-M7) are directed against flavoenzymes with covalently bound FAD. 952 96

Adriamycin (ADR) is a potent anticancer drug that causes severe cardiomyopathy. We have previously demonstrated that ADR-induced ultrastructural mitochondrial injury in the heart was attenuated in manganese superoxide dismutase (MnSOD) transgenic mice. To further investigate the biochemical mechanisms by which MnSOD protected mitochondria against ADR-induced damage, cardiac mitochondrial function and activities were evaluated. The results showed that ADR caused significant decrease in state 3 respiration and respiratory control ratio using both complex I and II substrates in nontransgenic mice. In transgenic mice, state 3 respiration for complex I substrates remained unaffected by ADR, but was reduced for complex II substrate. Complex I activity was significantly decreased in nontransgenic, but not in transgenic mice after ADR treatment, suggesting that mitochondrial complex I is sensitive to inactivation by superoxide radicals. The activities of complex II and mitochondrial creatine kinase were decreased by ADR in both nontransgenic and transgenic mice. These results support our previous observations on the protective role of MnSOD on the ultrastructural damage of the heart after ADR treatment and extend the understanding of its mechanisms in mitochondria.
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PMID:Manganese superoxide dismutase protects mitochondrial complex I against adriamycin-induced cardiomyopathy in transgenic mice. 991 29


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