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)

Ischemia/reperfusion mechanisms contribute to lung injury after transplantation, pulmonary embolism, and resolution of atelectasis. Alveolar tissue becomes hypoxic and deprived of substrate only when both ventilation and perfusion are interrupted, a situation modeled in vivo by complete, unilateral lung collapse. Because previously hypoxic mitochondria may be an important intracellular source of superoxide and hydrogen peroxide (H2O2) during reperfusion and re-oxygenation, the authors, in this study, investigated whether mitochondrial H2O2 release changed as a result of lung hypoxia/hypoperfusion resulting from collapse. Mitochondria were isolated from hypoxic (previously collapsed) right or contralateral left rabbits' lungs and from control rabbits' lungs. Mitochondrial H2O2 release, a marker of superoxide production, was measured fluorometrically after incubation with or without 1 mmol/L cyanide and 0.1 mmol/L nicotinamide adenine dinucleotide. Mitochondrial recovery was determined by assaying succinate dehydrogenase activity in mitochondrial preparations and lung homogenates. Lung succinate dehydrogenase activity and mitochondrial recovery were comparable among groups. Calculated lung mitochondrial content did not change (control subjects: left 7.9 +/- 0.5, right 13.8 +/- 1.7; hypoxic: left 10.3 +/- 1.3, right 10.5 +/- 2.4, all mg mitochondrial protein/lung). Mitochondria released hydrogen peroxide at approximately 5.6 nmol/h/mg pro in buffer alone and 14.8 nmol/h/mg pro in buffer with cyanide and nicotinamide adenine dinucleotide. However, lung collapse and resulting hypoxia caused no change in mitochondrial number or capacity to release H2O2 in vitro. Based on these findings, it is suggested that other sources of reactive oxygen metabolites, including xanthine oxidase and activated neutrophils, contribute to the oxidant injury observed in this model.
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PMID:Hydrogen peroxide release by mitochondria from normal and hypoxic lungs. 794 83

Male Sprague-Dawley rats aged 3 weeks that were maintained on an iron-deficient diet for 4-5 weeks developed severe anemia with markedly reduced hemoglobin levels (3.94 +/- 0.14 Hb g% versus controls 12.9 +/- 0.11 Hb g%). Iron-deficiency resulted in marked cardiac hypertrophy (cardiomegaly). On sacrifice, the hearts were processed for light and transmission electron microscopy. The major ultrastructural changes were found in the hypertrophied left ventricle and left papillary muscles. Iron-deficiency caused marked edema in myocytes, sarcomeres were out of register, and degeneration and discontinuities in myofilaments were common. Iron-deficiency resulted in the enlargement of the interfibrillar mitochondria, changes in the matrix and the formation of electron-dense amorphous bodies. The ultrastructural changes in myocytes in response to experimental iron-deficiency were similar to those described by others in cases of experimental ischemia or hypoxia. Mitochondrial changes were also found in the atria of iron-deficient rats. Quantitative cytochemical measurement of succinate dehydrogenase activity was determined and was shown to be substantially reduced in the iron-deficient heart. In severely iron-deficient rats restored to a normal iron-sufficient diet for two weeks, hemoglobin levels recovered, however the myocytes of the hypertrophied left ventricles and papillary muscles continued to show severe degenerative changes.
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PMID:Ultrastructural and cytochemical changes in the heart of iron-deficient rats. 820 92

The level of mRNA for cytochrome c oxidase subunit I (COX-I), which is encoded by mitochondrial DNA (mtDNA), progressively decreased in the hippocampal CA1 neurons of gerbils from 1-3 h of the reperfusion after 3.5 min of transient forebrain ischemia, and completely disappeared at 7 days. The activity of cytochrome c oxidase (COX) protein also showed the early decrease in the CA1 cells, and was followed by the reduction of the level of COX-I DNA after 2 days. However, the activity of succinic dehydrogenase (SDH), a mitochondrial enzyme that is encoded by nuclear DNA, maintained normal activity until 1 day in the CA1 cells, and significantly decreased at 7 days. These results suggest that the early onset and the progressive disturbance of a mitochondrial DNA expression found selectively in the CA1 neurons could cause progressive failure of energy production of the cells that eventually results in the neuronal cell death.
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PMID:Early disturbance of a mitochondrial DNA expression in gerbil hippocampus after transient forebrain ischemia. 839 54

Hippocampal CA1 neurons are the most vulnerable to transient cerebral ischemia. However, the mechanism has not been fully understood. The level of mRNA for cytochrome C oxidase (COX) subunit I (COX-I), which is encoded by mitochondrial (mt) DNA, progressively decreased in the hippocampal CA1 neurons of gerbils from 3 h of reperfusion after 3.5 min of transient forebrain ischemia and completely disappeared at 7 days. The activity of COX protein also showed an early decrease in CA1 cells and was followed by reduction of the level of COX-I DNA after 2 days. However, succinic dehydrogenase, an mt enzyme encoded by nuclear DNA, maintained normal activity until 1 day in the CA1 cells and significantly decreased at 7 days. The mRNA for mt heat shock protein (HSP) 60 began to increase at 3 h in the CA1 cells and was sustained until 1 day. The mRNAs for 72-kDa heat shock protein and 73-kDa heat shock cognate protein, which are located mainly in the cytoplasm, were induced together in the CA1 cells with a peak at 1-2 days. These results suggest that a disturbance of mt DNA expression occurred in the CA1 neurons at the early stage of reperfusion and was aggravated over the course of time. The disturbance could cause progressive failure of energy production of the cells that eventually results in neuronal cell death.
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PMID:Changes of mitochondrial DNA and heat shock protein gene expressions in gerbil hippocampus after transient forebrain ischemia. 839 36

Hippocampal CA1 neurons are the most vulnerable to transient cerebral ischemia. However, the mechanism has not been fully understood. The level of mRNA for cytochrome c oxidase subunit I (COX-I), which is encoded by mitochondrial DNA (mtDNA), progressively decreased in the hippocampal CA1 neurons of gerbils from 1 to 3 h of the reperfusion after 3.5 min of transient forebrain ischemia, and completely disappeared at 7 days. The activity of cytochrome c oxidase (COX) protein also showed the early decrease in the CA1 cells, and was followed by the reduction of the level of COX-I DNA after 2 days. However, the activity of succinic dehydrogenase (SDH), a mitochondrial enzyme that is encoded by nuclear DNA, maintained normal activity until 1 day in the CA1 cells, and significantly decreased at 7 days. These results suggest that disturbance of mitochondrial DNA expression occurred in the CA1 neurons at the early stage of reperfusion, and was aggravated in the course of time. The disturbance could cause progressive failure of energy production of the cells that eventually results in the neuronal cell death.
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PMID:Disturbance of a mitochondrial DNA expression in gerbil hippocampus after transient forebrain ischemia. 839 30

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.
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PMID:Histochemical detection of glycogen phosphorylase activity as parameter for early ischemic damage in rat heart. 850 31

Repeatedly it was reported that a short ischemic episode may ameliorate biochemical and morphological impairment upon succeeding severe ischemia. We investigated whether the pattern of respiratory enzyme activity (RA), adenine nucleotides, and membrane potential in hippocampal slices following low-dose in vivo (20 mg/kg) and high-dose in vitro (1 mM) application of 3-nitropropionic acid (3-np), a specific inhibitor of succinic dehydrogenase (SDH), indicates a similar tolerance phenomenon. One hour in vivo treatment decreased RA, spectrophotometrically quantitated by intensity of staining with 2,3,5-triphenyltetrazolium chloride (TTC), to 48 +/- 5% (mean +/- SE; P<0.01). Intermittent increase after 2 h (79 +/- 5%; P<0.05) was followed by gradual decline to 48 +/- 16% (P<0.01) after 8 h. The intermittent increase predominated in stratum pyramidale of hippocampal region CA1 (CA1sp) vs CA3 (CA3sp) (89 +/- 6% vs 57 +/- 6% of control; P <0.01). ATP levels paralleled the intensity of average (CA1sp, CA3sp, plus CA1 stratum radiatum) TTC staining (r=0.93). After pretreatment of 3-np in vivo for 1 h, no further decrease of RA upon 30-min in vitro treatment was seen in any region. At all other times, RA declined further upon in vitro treatment (P<0.01). Compared to 1-h in vivo treatment, hyperpolarization of CA1sp pyramidal cells upon in vitro application of 1 mM 3-np was reduced after 8-h pretreatment in vivo (P<0.04). At this time, depolarization upon glibenclamide (10 muM), an antagonist at KATP-channels, was reduced. We conclude that the severity of impairment of oxidative phosphorylation upon repeated inhibition of SDH in vivo and in vitro is not increased in an additive manner. At appropriate times, relative protection against further decrease of energy metabolism is observed-chemical preconditioning. Activation of KATP-channels is associated with chemical preconditioning.
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PMID:Mitochondrial oxidation in rat hippocampus can be preconditioned by selective chemical inhibition of succinic dehydrogenase. 859 90

Emergencies which were different in origin, but identical in the magnitude of pathogenic action on the brain, such as 3.5-hour cerebral circulatory ischemia found 49-hour restriction stress, induced the the same brain mitochondrial responses in Wistar rats. Two types of responses in organelles were identified: (1) that wherein there were lower succinate oxidation rates than those in the control (sham = operated and intact animals) and diverted effects on succinate dehydrogenase activators; (2) that wherein there was accelerated succinate oxidation and persisted stimulating effects of enzyme activators. A relationship was shown between the type of responses and the degree of succinate dehydrogenase inhibition induced by emergencies.
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PMID:[Effect of extreme conditions on succinate oxidation in rat brain mitochondria]. 865 45

We examined regional differences in the activity of a mitochondrial respiratory enzyme, succinic dehydrogenase (SDH), in the hippocampi of normal and postischemic gerbils, using a quantitative imaging method. Gerbils (n = 21) without ischemia, and gerbils which had experienced 5 min of bilateral common carotid artery occlusion 12 h or 2 days previously, were sacrificed. Coronal sections of the brains were prepared for quantitative imaging of SDH activity and histological examination. In the control gerbils, SDH activity in the pyramidal cell layer of the CA 1 sector (Sommer's sector) was 106.3 +/- 10.3% (mean +/- SD; SDH activity as a percentage of the cerebellar SDH activity), which was lower than in the other subfields of the hippocampus. SDH activity in the oriens layer, stratum radiatum and lacunosum molecular layer of the CA 1 sector was lower than in the corresponding layers of the CA 2 and CA 3 sectors. After transient ischemia, SDH activity remained unchanged in the CA 1 sector. Histologically, selective neuronal necrosis was observed in the pyramidal cell layer of the CA 1 sector 2 days after ischemia. The observed low level of this mitochondrial respiratory enzyme in the pyramidal cell layer of the CA 1 sector should be taken into account as a possible trigger of the selective vulnerability of the region to ischemia.
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PMID:The pyramidal cell layer of sector CA 1 shows the lowest hippocampal succinate dehydrogenase activity in normal and postischemic gerbils. 871 Jan 65

A subtraction cDNA library was made using subtractive hybridization of cDNA libraries constructed from gerbil cerebral cortex of control animals and animals 8 hours after a 10-min transient forebrain ischemia. After differential screening, a cDNA clone (named pGSH3) was isolated as a gene that is expressed only after the ischemic insult. The cDNA insert of pGSH3 (0.7 kb) hybridized to the 2.8-kb mRNA of ischemic cerebral cortex. The gene was normally expressed in a small amount in the cerebellum, kidney, and lung, but was not expressed in the cerebral cortex, heart, liver, or jejunum in a detectable amount. Eight hours after the 10-min transient forebrain ischemia, the gene expression became prominent in the cerebral cortex, and the amount of the mRNA also increased in the lung and kidney. An analysis of DNA sequence revealed that the pGSH3 insert has a 91.3% homology with a 72-kd human heat-shock protein (hsp70) gene. These results indicate that an ischemia-induced gene was isolated as a cDNA clone (pGSH3) by subreactive hybridization and differential screening. Expression of the gene was detected in other organs especially in the kidney and lung after transient forebrain ischemia. Hippocampal CA1 neurons are the most vulnerable to transient cerebral ischemia. However, the mechanism has not been fully understood. The level of mRNA for cytochrome C oxidase subunit I (COX-I), which is encoded by mitochondrial DNA (mtDNA), progressively deceased in the hippocampal CA1 neurons of gerbils from 3 hours of the reperfusion after 3.5 min of transient forebrain ischemia, and completely disappeared at 7 days. The activity of cytochrome C oxidase (COX) protein also showed the early decrease in the CA1 cells, and was followed by the reduction of the level of COX-I DNA after 2 days. However, the activity of succinic dehydrogenase (SDH), a mitochondrial enzyme that is encoded by nuclear DNA, maintained normal activity until day 1 in the CA1 cells, and significantly decreased at 7 days. The mRNA for mitochondrial hsp60 began to increase at 3 hours in the CA1 cells, and was sustained until 1 day. The mRNAs for 72-kd (hsp70) and 73-kd (hsc70) heat-shock proteins, which are mainly located in the cytoplasm, were induced together in the CA1 cells with a peak at 1 to 2 days. These results suggest that disturbance of a mitochondrial DNA expression occurred in the CA1 neurons at the early stage of reperfusion, and was aggravated in the course of time. The disturbance could cause progressive failure of energy production of the cells, which eventually results in neuronal cell death.
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PMID:Isolation of an ischemia-induced gene and early disturbance of mitochondrial DNA expression after transient forebrain ischemia. 879 Aug 23


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