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)

1. The present study was designed to determine whether naftidrofuryl oxalate exerts a possible therapeutic effect on brain energy metabolism impaired by microsphere-induced cerebral embolism in vitro. 2. Injection of microspheres into the right carotid canal resulted in a decrease in tissue high-energy phosphates both in the right and left hemispheres, and an increase in tissue lactate in the right hemisphere, on the 3rd and the 5th day after the embolism. The embolism also induced a marked reduction in mitochondrial oxidative phosphorylation ability and succinate dehydrogenase activity. The results suggest that severe ischaemia was induced in the brain by the microsphere administration. 3. Treatment of microsphere-injected rats with naftidrofuryl oxalate (15 mg kg-1) for 3 or 5 days elicited a significant recovery of tissue high-energy phosphate and lactate levels. The recovery was associated with a significant restoration of mitochondrial succinate dehydrogenase activity on the both days and of mitochondrial oxidative phosphorylation rate on the 5th day. 4. The results suggest that naftidrofuryl oxalate is beneficial in the recovery of cerebral energy metabolism impaired by microsphere-induced cerebral ischaemia, presumably through a mechanism involving its direct effect on the cerebral mitochondrial enzyme activities.
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PMID:Possible therapeutic effect of naftidrofuryl oxalate on brain energy metabolism after microsphere-induced cerebral embolism. 281 26

The effect of reperfusion following 30 min of cerebral ischaemia on brain mitochondrial respiratory chain activity has been studied in the gerbil. The state 3 respiration rates with both FAD- and NAD-linked substrates were reduced after ischaemia. After 5 min of reperfusion, state 3 respiration with FAD-linked substrates was restored, but levels of NAD-linked substrates did not return to control values until 30 min of reperfusion. By 120 min of reperfusion state 3 respiration decreased relative to control values with all substrates studied. Measurement of the individual respiratory chain complexes showed that complex I, complex II-III, and complex V activities were reduced after ischaemia. By 5 min of reperfusion complex II-III activity was restored, but the activities of complexes I and V did not return to control values until 30 min of reperfusion. In contrast, complex IV activity was unaffected by ischaemia or 5 and 30 min of reperfusion but was significantly reduced after 120 min of reperfusion, possibly owing to free radical production and lipid peroxidation.
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PMID:Effect of reperfusion following cerebral ischaemia on the activity of the mitochondrial respiratory chain in the gerbil brain. 756 67

In this study we have examined (1) the integrated function of the mitochondrial respiratory chain by polarographic measurements and (2) the activities of the respiratory chain complexes I, II-III, and IV as well as the ATP synthase (complex V) in free mitochondria and synaptosomes isolated from gerbil brain, after a 30-min period of graded cerebral ischaemia. These data have been correlated with cerebral blood flow (CBF) values as measured by the hydrogen clearance technique. Integrated functioning of the mitochondrial respiratory chain, using both NAD-linked and FAD-linked substrates, was initially affected at CBF values of approximately 35 ml 100 g-1 min-1, and declined further as the CBF was reduced. The individual mitochondrial respiratory chain complexes, however, showed differences in sensitivity to graded cerebral ischaemia. Complex I activities decreased sharply at blood flows below approximately 30 ml 100 g-1 min-1 (mitochondria and synaptosomes) and complex II-III activities decreased at blood flows below 20 ml 100 g-1 min-1 (mitochondria) and 35-30 ml 100 g-1 min-1 (synaptosomes). Activities declined further as CBF was reduced below these levels. Complex V activity was significantly affected only when the blood flow was reduced below 15-10 ml 100 g-1 min-1 (mitochondria and synaptosomes). In contrast, complex IV activity was unaffected by graded cerebral ischaemia, even at very low CBF levels.
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PMID:Changes of respiratory chain activity in mitochondrial and synaptosomal fractions isolated from the gerbil brain after graded ischaemia. 772 7

Some of the basic biomechanical properties of edematous brain tissue have yet to be clarified. Therefore we measured regional tissue compliance and swelling isotropy/anisotropy in cat brain during development of vasogenic-type and cytotoxic-type edema. In vasogenic-type edema induced by cryogenic injury, the edematous white matter showed an increase of regional tissue compliance (indentation method), which paralleled the increase in the regional tissue water content (gravimetry). Swelling of the white matter due to edema was anisotropic, in which expansion transverse to the neuronal fibers caused by their dissociation was 91.1%, whereas longitudinal expansion was 2.3%. In cytotoxic-type edema induced by cerebral ischemia for 3 h, regional tissue compliance was decreased in the area suffering energy failure, which was visualized as an area of reduced succinic dehydrogenase activity. The ischemic gray matter showed isotropic swelling, and morphologically, prominent swelling of neuroglial cells. These marked differences in basic biomechanical properties between vasogenic-type and cytotoxic-type edema should be taken into account when analyzing the mechanism of edema-mediated tissue injury.
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PMID:Biomechanical characteristics of brain edema: the difference between vasogenic-type and cytotoxic-type edema. 797 33

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

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

The distribution of succinate dehydrogenase (SDH) activity and the corresponding changes in specific gravity were studied in cats with experimental focal ischemia. Two hours of tandem occlusion of the middle cerebral artery (MCA) and the conunon carotid artery produced a scattered reduction of SDH activity and corresponding brain edema in the cortex. Recirculation ameliorated the SDH reduction and the scattered pattern disappeared, although the brain edema increased further. Four hours of focal ischemia resulted in diffuse reduction of SDH activity in the MCA-perfused area. The scattered area of SDH reduction after 2 hours of focal cerebral ischemia indicates that the ischemic core is multicentric in the early phase, and that these areas fuse together to form a well demarcated infarction, if the blood flow is not reestablished. A short period of cerebral ischemia produces multicentric small infarcts in the cortex, which resemble granular atrophy.
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PMID:Heterogeneous distribution of early energy failure in experimental focal ischemia of the cat brain. 941 75

In order to test the effect of hypothermia on mitochondrial function damage following cerebral ischaemia/reperfusion, Mongolian gerbils were submitted to 30 min bilateral carotid occlusion and 2 h of reperfusion at 37 degreesC or 30 degreesC. After normothermic (37 degreesC) ischaemia/reperfusion, significant decreases in mitochondrial state 3 (+ADP) oxygen consumption (-42.2%), complex II-III activity in synaptosomes (-31.7%) and complex IV were measured, in both free mitochondria and synaptosomes (-30.3% and -27. 8% respectively). However, following hypothermic (30 degreesC) reperfusion, both respiration rates and all enzyme activities remained at levels not significantly different from those in the sham operated controls.
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PMID:Effect of postischaemic hypothermia on the mitochondrial damage induced by ischaemia and reperfusion in the gerbil. 988 78

Intrastriatal injection of the reversible succinate dehydrogenase inhibitor malonate produces both energy depletion and striatal lesions similar to that seen in cerebral ischemia and Huntington's disease. The mechanisms of neuronal cell death involve secondary excitotoxicity and the generation of reactive oxygen species. Here, we investigated the effects of dopamine on malonate-induced generation of hydroxyl radicals and striatal lesion volumes. Using in vivo microdialysis, we found that malonate induced a 94-fold increase in extracellular striatal dopamine concentrations. This was paralleled by an increase in the generation of hydroxyl radicals. Prior unilateral lesioning of the nigrostriatal dopaminergic pathway by focal injection of 6-hydroxydopamine blocked the malonate-induced increase in dopamine concentrations and the generation of hydroxyl radicals and attenuated the lesion volume. In contrast, the NMDA receptor antagonist MK-801 attenuated malonate-induced lesion volumes but did not block the generation of hydroxyl radicals. Thus, the dopaminergic and glutamatergic pathways are essential in the pathogenesis of malonate-induced striatal lesions. Our results suggest that the malonate-induced release of dopamine but not NMDA receptor activation mediates hydroxyl radical formation.
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PMID:Malonate-induced generation of reactive oxygen species in rat striatum depends on dopamine release but not on NMDA receptor activation. 1046 28


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