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)

Functional and structural alterations of myocardial mitochondria were investigated after four conditions of myocardial ischaemia in guinea pig heart: (1) 45 min complete ischaemia, (2) 60 min low-flow anoxic perfusion (0.3 ml/g wet weight per minute) with a modified Tyrode solution, (3) as (2) with 0.4 mM palmitic acid added to the perfusate, and (4) as (2) with 0.4 mM oleic acid added. Under conditions (1) and (2) the loss of tissue ATP (20-30% of aerobic control) and the degree of mitochondrial injury were similar. But when fatty acids were present during low-flow anoxia, ATP loss and mitochondrial injury were more severe. Oleic acid caused greater injury than palmitic acid. The extent of mitochondrial injury corresponded to variations in mitochondrial long-chain acyl CoA content. Compared to aerobic control values, acyl CoA was increased 1.5 fold under condition (1), not significantly altered under condition (2), increased 3.2 fold under condition (3) and increased 4.3 fold under condition (4). In low-flow anoxia fatty acids enhanced the depression of oxidative phosphorylation, the loss of cytochromes, the inhibition of adenine nucleotide translocase and the reduction of mitochondrial Ca2+ sequestration. Fatty acid induced injury differed in quality from that of conditions (1) and (2): complex II dependent respiration was markedly affected, cytochrome b was lost extensively, and cytochrome oxidase activity was distinctly reduced. The results indicate that fatty acids, when administered to ischaemic myocardium, interfere with mitochondrial membranes at several sites, probably by their CoA esters. The more lipophilic oleyl moiety has a greater effect than the palmityl moiety.
Basic Res Cardiol 1987
PMID:Detrimental actions of endogenous fatty acids and their derivatives. A study of ischaemic mitochondrial injury. 282 81

The effects of revascularization on the morphological aspects of myocardial infarction have been studied in 87 animals. After permanent ligation of a coronary artery, the aspects are stereotyped and the histo-enzymatic and ultrastructural evolution is quite well known. On the contrary, early revascularization of this infarction at different times causes specific alterations: alteration of the membrane permeability with an intense edema of myocardial cells, restriction of the negative succinate dehydrogenase zone, cleavage of the sarcolemma membrane, intra-mitochondrial calcium deposits and destruction of endothelial membranes. These lesions are responsible for the non-revascularization phenomenon which limits considerably the metabolic recovery of the ischemic area. These spectacular membrane destructions of the revascularization could be linked to the release of free radicals. Besides, the use of Mannitol and Allopurinol, with their known protective effect on the free radicals, enables to greatly reduce the size of the resulting infarction (60 animals). 12 patients, after failure of a coronary dilatation, were treated in the first six hours with a cardioplegic perfusion with allopurinol followed by a by-pass. The long term results show the retrogression of the Q waves in 11 out of 12 cases and the functional recovery of the akinetic area on the echocardiogram.
Ann Cardiol Angeiol (Paris) 1986 Oct 15
PMID:[Membrane modifications in myocardial infarction following emergency reperfusion]. 380 Feb 86

Heart rate in mammals is inversely related to body weight. In the etruscan shrew it exceeds 960 beats/min. Since the heart depends primarily on energy from aerobic sources, it was interesting to examine some morphological parameters of the mitochondria in some mammals with a high heart frequency. Volume fraction and surface to volume ratio of the mitochondria in the myocardium were determined in the white rat (221 g), white mouse (36 g), white-toothed shrew (8 g) and the etruscan shrew (2 g) using morphometric methods. The volume fraction and surface to volume ratio of the mitochondria increased progressively and significantly as body weight of the animal decreased. The increase was higher in the surface to volume ratio than in the volume fraction. It reached a value which was 62% higher in the etruscan shrew than that of the white rat, while in the volume fraction of the mitochondria the maximal increase was only 34%. In accordance with the morphometric data, enzymatic activity of succinic dehydrogenase in the myocardium was inversely related to body weight. Creatine phosphokinase activity revealed a similar but not statistically significant trend. Lactic dehydrogenase activity was about three-fold higher in the white rat than in the white toothed shrew. It is concluded that one of the adaptive responses of the heart in small sized mammals to increase ATP production is not only elevation of the volume fraction of the mitochondria, but also an increase of their surface to volume ratio to provide a higher rate of oxygen diffusion to them.
J Mol Cell Cardiol 1985 Jun
PMID:Comparative morphometry of the mitochondria and activity of some enzymes in the myocardium of small mammals. 402 Aug 80

We studied the effects of running-training, heavy exercise and termination of training on the heart weight, the ratio heart to body weight and the cardiac muscle activities of actomyosin ATPase, citrate synthase, succinate dehydrogenase, cytochrome c oxidase, malate dehydrogenase, adenylate kinase and beta-glucuronidase with adult male NMRI-mice. Stable hypertrophy (6-7%), estimated by the ratio heart or ventricle weight to body weight, was achieved by 28 exercises and it was dependent on the running speed (20 vs. 25 m X min-1). The withdrawal of training for 5-61 days did not permanently decrease the heart weight or the heart to body weight ratio to the level of sedentary controls. The activity of enzymes of energy metabolism or actomyosin ATPase were not affected by training, heavy exercise or terminated training. beta-glucuronidase activity slightly (20-25%) increased in the trained animals and remained at a higher level during the period of terminated training. The results suggest that the capacity for aerobic metabolism of normal mice heart is sufficient to meet the enhanced demand for ATP imposed by running-training and that the heart enlargement occurs in equal proportions with the enzymatic potential of the cardiac tissue.
Basic Res Cardiol
PMID:Selected enzyme activities in mouse cardiac muscle during training and terminated training. 623 64

Histochemical alterations of acute and chronic doxorubicin (DOX) cardiotoxicity in the mouse were assessed by the localization of succinate dehydrogenase (SDH), coenzyme Q10 (CoQ), cytochrome oxidase (COX), creatine phosphokinase (CPK), lactate dehydrogenase (LDH), reduced glutathione (GSH), and intracellular calcium. Isolated myocytes intensely stained for calcium were found at 72 and 120 h under the acute protocol; altered staining patterns of SDH, CoQ, and COX, were evident at 120 h. Chronically, two patterns of intracellular calcium staining were evident: (1) intensely stained myocytes as found in the acute protocol; and (2) multiple discrete intracellular deposits suggestive of mitochondrial localization. Altered staining patterns of SDH, CoQ, COX, CPK, and LDH under the chronic protocol were only seen after abnormal staining was evident in trichrome stained sections. The presence of characteristic vacuolated myocardial cells in both acute and chronic protocols was confirmed by one micron epon-embedded toluidine blue stained sections and electron microscopy. These histochemical findings suggest that DOX alters the functional integrity of mitochondrial respiratory chain enzymes in the myocardial cell.
J Mol Cell Cardiol 1983 Aug
PMID:Histochemical alterations of acute and chronic doxorubicin cardiotoxicity. 667 10

To study whether heterogeneous myocardial blood flow relates to the local oxidative capacity of cardiac muscle, local blood flow at resting cardiac workloads and the activity of the mitochondrial enzyme succinate dehydrogenase (SDH) were determined in small regions of the left ventricle of seven anaesthetized, mechanically ventilated, open-chest pigs (25-35 kg). Following injection of radioactive microspheres (15 microns phi) into the left atrium, the heart was rapidly excised and cut into five transverse slices, which were simultaneously freeze-clamped between two aluminum blocks precooled at -80 degrees C. The left ventricle was then subdivided into 84 samples of about 0.9 g. Myocardial blood flow was 0.88 +/- 0.34 ml/min/g wet weight (ww), and SDH activity 1.46 +/- 0.33 mumol/min/g ww (mean +/- S.D., n = 7). Local data were normalized to their respective mean values in each pig, and then pooled. Local blood flow ranged from 0.32 to 1.63 of the mean, and blood flow heterogeneity characterized by the coefficient of variation (CV = S.D./mean) was 18.4%. Normalized local SDH activity ranged from 0.16 to 1.94, with a CV of 21.8%, significantly exceeding measurement error (CV = 4.5%). Local blood flows and SDH activities did not vary among transmural sublayers of the left ventricle, but variation within each sublayer was considerable. In six of the seven pigs, local blood flow correlated (P < 0.05) with SDH activity, with correlation coefficients (r) ranging from 0.26 to 0.54 (for pooled data: r = 0.27, P < 0.0001). When expressed per gram dry weight, heterogeneity of SDH activity increased (P < 0.05), and here also local blood flow correlated with SDH activity in all pigs (for pooled data: r = 0.45, P < 0.0001). Hence, heterogeneity of mitochondrial capacity within cardiac muscle partly explains the heterogeneity of myocardial blood flow, even though myocardial perfusion at rest was studied in relation with a maximal enzyme rate. The low correlation coefficient clearly indicates that at resting workloads other factors also play a role.
J Mol Cell Cardiol 1994 Aug
PMID:Local mitochondrial enzyme activity correlates with myocardial blood flow at basal workloads. 779 42

In the present study we have investigated whether enzyme histochemical parameters can be applied to detect early ischemic damage in rat heart after ischemia without restoration of the blood flow. Ischemia was induced by incubating heart fragments for 0, 10, 20, 30, 60, 120 and 240 min at 37 degrees C. The activity and localization of the following enzymes was studied in unfixed cryostat sections using quantitative histochemical methods: lactate dehydrogenase, creatine kinase, succinate dehydrogenase, phosphofructokinase, acid phosphatase, 5'-nucleotidase and glycogen phosphorylase. Moreover, the ultrastructure of the tissue was studied with special attention to the appearance of flocculent densities in mitochondria, which can be seen as a sign of irreversible cell damage. It was shown that glycogen phosphorylase activity in rat heart decreased after short periods (30 min) of in vitro ischemia, whereas all other enzymes studied were not decreased up to 240 min, with the exception of lactate dehydrogenase and phosphofructokinase activities which were diminished only at 240 and 120 min of ischemia, respectively. Some reaction product was found after incubating for 5'-nucleotidase activity in the absence of substrate, indicating the presence of endogenous substrate(s). This endogenous substrate disappeared from the myocytes after 20 min of ischemia. It is assumed that AMP and/or other phosphate-containing compounds play an essential role in the activation of glycogen phosphorylase. Significant reduction of glycogen phosphorylase activity is correlated with the irreversible stage of damage of myocytes as judged from the ultrastructure.
Basic Res Cardiol
PMID:Histochemical detection of glycogen phosphorylase activity as parameter for early ischemic damage in rat heart. 850 31

Congestive heart failure is often associated with skeletal muscle abnormalities that contribute to early fatigue and acidosis. Up to the present time, however, the mechanisms responsible for these changes are unclear. Myocardial infarctions were produced by coronary ligation in adult Sprague-Dawley rats. At 20 weeks, 10 control rats, and 15 animals with heart failure [defined by elevated LVEDP (26.1 +/- 3.1 v 2.5 +/- 0.5 mmHg) and RV hypertrophy (300 +/- 21 g v 158 +/- 9 mg)] underwent in vivo measurements of total body, and soleus total protein and myosin heavy chain (MHC) synthesis by [3H]leucine constant infusion. Soleus muscle was also analysed for protein content, and MHC isoenzyme content by SDS-PAGE. Northern blotting also was used to determine levels of the mRNA's encoding type I, IIa, IIb, and IIx MHC, alpha-skeletal actin, COX III, SDH and GAPDH. Soleus muscles in heart failure rats were smaller than controls (112 +/- 6 v 126 +/- 5 mg) and the degree of atrophy was significant when corrected for body mass (0.38 +/- 0.02 v 0.46 +/- 0.02 mg/g. P = 0.007). Although there was no significant difference in plasma leucine flux (an index of whole-body protein synthesis), soleus muscle total and MHC synthesis was reduced in heart failure animals. Whereas the Type I MHC isoenzyme (beta MHC) was the only MHC detected in the soleus of control animals, type II MHC isoenzyme comprised 11.8 +/- 3.1% of the MHC in the heart failure group. Furthermore, steady-state mRNA levels encoding beta MHC were significantly depressed in the heart failure rats, where those encoding Types IIb and IIx MHC were increased. Steady-state mRNA levels of alpha-skeletal actin, cytochrome C oxidase (COX III) and succinate dehydrogenase (SDH) were also significantly depressed. This animal model of chronic heart failure is associated with quantitative and qualitative alterations in skeletal muscle gene expression that are similar to those reported in skeletal muscle of patients with chronic heart failure. The altered phenotype and impaired metabolic capacity may contribute to exercise intolerance in CHF.
J Mol Cell Cardiol 1996 Aug
PMID:Alterations in skeletal muscle gene expression in the rat with chronic congestive heart failure. 887 78

We hypothesized that cardiac aging in the rat involves mitochondrial genetic damage and mitochondrial enzymatic dysfunction of individual cardiomyocytes as has been demonstrated previously only in primate myocardium. Myocardium from Fischer 344 x Brown Norway F(1)hybrid rats of ages 5, 18 and 36-38 months was examined for mitochondrial genetic and enzymatic abnormalities. In-vivo hemodynamic measurements revealed age-related changes of left ventricular function while histological evaluation demonstrated an increase in percent area fibrosis from 7%+/-5 in the 5-month-old hearts to 38%+/-2 in the subendocardium of the left ventricle of 38-month-old rats. Mitochondrial genomes lacking 8000 to 9000 bp of primary sequence were detected in tissue homogenates from right and left ventricular myocardium and the abundance of these deleted genomes increased with age. In-situ histochemical staining of serial cryomicrotome sections of myocardial tissue revealed individual cardiomyocytes displaying abnormal, primarily absent, activities of cytochrome c oxidase and succinate dehydrogenase. The area density of histochemically-abnormal cardiomyocytes increased from 0.05 per mm(2)to 0.3 per mm(2)between 5 and 36-38 months of age in the left ventricle, and they were localized primarily to the left ventricular subendocardium. The presence of age-related mitochondrial genetic and enzymatic abnormalities in the Fischer 344 x Brown Norway F(1)hybrid rat heart suggests the role of mitochondrial dysfunction, secondary to mtDNA mutations, in age-related cardiomyocyte loss and subsequent cardiac aging.
J Mol Cell Cardiol 2002 Jan
PMID:Age-associated changes in function, structure and mitochondrial genetic and enzymatic abnormalities in the Fischer 344 x Brown Norway F(1) hybrid rat heart. 1181 61

Thyroid hormone (TH) induces marked changes in the biochemical and physiological functioning of cardiac muscle affecting its bioenergetics, contractility and structure. Using a time-course analysis of in vitro treatment of neonatal rat cardiomyocytes with triiodothyronine (T3), mitochondrial biogenesis, functional bioenergetics and cardiomyocyte hypertrophic phenotype were assessed. Activity of respiratory complexes II, IV, V and citrate synthase (CS), levels of mitochondrial enzyme subunits (e.g. COXI, COXIV) and nuclear-encoded transcription factors, involved in mitochondrial biogenesis (e.g. PGC-1, mtTFA and PPAR-alpha), were significantly elevated with 72 h T3 treatment. A time-course analysis showed an early increase (between 3 and 12 h) in activity and levels of subunits of complex IV and V, mitochondrial Ca2+ accumulation and a late increase (at 72 h) in complex II and CS activities, mitochondrial protein content and mitochondrial respiration. Based on overall protein content and specific peptide levels (e.g. actin or myosin) only mild cardiomyocyte hypertrophy was detected. T3 mediates an early stimulation of enzymes containing mtDNA encoded subunits (e.g. complex IV and V) in contrast to a different regulatory pattern for the entirely nuclear-encoded enzymes (e.g. CS and complex II). T3-regulation was similar in both neonatal and young adult cardiomyocytes (ARCM) but absent in the senescent cardiomyocytes. This model offer an opportunity to study the rapid timing of events involved in myocardial cell signaling, bioenergetics and growth dynamics in a timeframe not available with whole animal studies.
J Mol Cell Cardiol 2005 Aug
PMID:Nuclear-mitochondrial cross-talk in cardiomyocyte T3 signaling: a time-course analysis. 1589 63


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