Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.4.3.11 (glutamate dehydrogenase)
4,437 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glutamate has been proposed to play a critical role in acute ischemic pathophysiology in the brain. In this study, glutamate was monitored by the dialysis electrode technique, in which glutamate is oxidized by glutamate oxidase producing hydrogen peroxide which is then amperometrically detected on a platinum electrode set at +650 mV vs Ag/AgCl. A dialysis electrode, which consists of a microdialysis probe with a built-in platinum electrode, provides a continuous glutamate oxidase perfusion inside of the probe. Perfusion with this solution allows real-time monitoring of glutamate dynamics in the extracellular space during ischemia. This study was designed to collect detailed information on rapid changes in the extracellular glutamate concentration of the rat striatum and demonstrated two distinct phases of glutamate release during early severe brain ischemia.
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PMID:Real time monitoring of biphasic glutamate release using dialysis electrode in rat acute brain ischemia. 880 58

Fructose-1,6-bisphosphate (FBP), an intermediate of glucose metabolism, is neuroprotective in brain hypoxia or ischemia. Because the mechanisms for this protection are not clear, we examined the effects of FBP on two important events in brain ischemia, i.e., loss of ATP and release of the excitatory neurotransmitter glutamate. Glutamate release from cortical brain slices was measured fluorometrically (glutamate dehydrogenase-catalyzed conversion of glutamate to alpha-ketoglutarate) during hypoxia (PO2 15 mm Hg) or hypoxia plus 100 microM cyanide. FBP (3.5 mM, with glucose 20 mM) reduced glutamate release during hypoxia by 55% and during hypoxia/cyanide by 46% (p < 0.005), and prevented a significant fall in [ATP]. [ATP] was maintained in oxygenated glucose-free conditions with 20 but not 3.5 mM FBP, and fell to < 20% of normal with hypoxia. Despite the drop in [ATP], 3.5 or 20 mM FBP without glucose decreased hypoxia-evoked glutamate release. We conclude (1) FBP present without glucose preserves normal [ATP] only when oxygen is available, suggesting limited uptake and metabolism; and (2) FBP decreases hypoxia-evoked glutamate release by processes independent of [ATP]. These results suggest protective actions of FBP that are separate from augmentation of anaerobic energy production, as previously proposed.
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PMID:Effects of fructose-1,6-bisphosphate on glutamate release and ATP loss from rat brain slices during hypoxia. 885 28

In 50 human livers harvested for transplantation, injury was assessed by determination of liver enzymes (lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, glutamate dehydrogenase, and creatine kinase) and of thrombomodulin in the effluent perfusate after cold ischemia. The results were compared with the morphology and the clinical course after transplantation. Whereas the release of the markers of endothelial cell injury correlated neither with the history of the graft nor with the postoperative course, the release of hepatocellular enzymes into the perfusate did indicate the severity of liver injury, even when biopsy showed normal liver tissue. Seven of 12 livers with high activities of hepatocellular enzymes in the effluent (activity of more than twice the median) showed delayed onset of function or primary nonfunction. In the other 38 livers with enzyme activities below this borderline, no delayed functioning or primary nonfunction was observed. Thus, determination of liver enzyme activities in the effluent makes it possible to identify those livers in which initial nonfunction is very unlikely, a potential that is especially valuable in livers shown by anamnesis or morphology to be of borderline quality.
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PMID:Determination of hepatocellular enzymes in effluent of human liver grafts for preoperative evaluation of transplant quality. 893 67

Glutamate is believed to be an excitatory amino acid neurotransmitter in the retina. Enzymes for glutamate metabolism, such as glutamate dehydrogenase, ornithine aminotransferase, glutaminase, and aspartate aminotransferase (AAT), exist mainly in the mitochondria. The abnormal increase of intracellular calcium ions in ischemic retinal cells may cause an influx of calcium ions into the mitochondria, subsequently affecting various mitochondrial enzyme activities through the activity of mitochondrial calpain. As AAT has the highest level of activity among enzymes involved in glutamate metabolism, we investigated the change of AAT activity in ischemic and hypoxic rat retinas and the protection against such activity by calpain inhibitors. We used normal RCS (rdy+/rdy+) rats. For the in vivo studies, we clamped the optic nerve of anesthetized rats to induce ischemia. In the in vitro studies, the eye cups were incubated with Locke's solution saturated with 95% N2/5% CO2. The activity of cytosolic AAT (cAAT) was about 20% of total activity, whereas mitochondrial AAT (mAAT) was about 75% in rat retina. Ninety minutes of ischemia or hypoxia caused a 20% decrease in mAAT activity, whereas cAAT activity remained unchanged. To examine the contribution of intracellular calcium ions to the degradation of mAAT, we used Ca2+-free Locke's solution containing 1 mM EGTA, ryanodine (Ca2+ channel blocker), and thapsigargin (Ca2+-ATPase inhibitor). In the present study, thapsigargin in Ca2+-free Locke's solution, but not ryanodine in this solution, was found to prevent AAT degradation. AAT degradation was also prevented by calpain inhibitors (Ca2+-dependent protease inhibitor) such as calpeptin at 1 nM, 10 nM, 0.1 microM, 1 microM and 10 microM, and by calpain inhibitor peptide, but not by other protease inhibitors (10 microM leupeptin, pepstatin, chymostatin). Additionally, we determined the subcellular localization of calpain activity and examined the change of calpain activity in ischemic rat retinas. Our results suggest that decreased activity of mAAT in ischemic and hypoxic rat retinas might be evoked by the degradation by calpain-catalyzed proteolysis in mitochondria.
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PMID:Possible mechanism for the decrease of mitochondrial aspartate aminotransferase activity in ischemic and hypoxic rat retinas. 1039 49

The difference in ischemic tolerance between the retina and cerebral cortex may be attributable to a difference in glutamate release during ischemia. Glutamate release in the retina and the cerebral cortex was compared in rats. A dialysis electrode for real-time glutamate measurement was perfused with L-glutamate oxidase, and the current evoked between two voltage-clamped electrodes was detected. Two electrodes were implanted in the retina through the choroid and cerebral cortex in 12 anesthetized rats, each mounted on a stereotaxic frame. Global ischemia was induced by ligation on both carotid arteries and hypotension was induced by blood withdrawal. Under control conditions, the glutamate concentration in the retina was 164 +/- 231 (mean +/- standard deviation) microM, being significantly higher (P < 0.05) than that in the cerebral cortex (83 +/- 105 microM). In 10 of the 12 animals, the glutamate concentration in the retina decreased to a minimum of 134 +/- 149 microM (P < 0.01, compared with the value for the cerebral cortex), but that in the cortex increased to 410 +/- 305 microM (averaged highest value). Immediately after the start of reperfusion, the glutamate concentration in the cortex decreased rapidly to 101 +/- 27 microM, but that in the retina increased gradually to almost the control level (148 +/- 204 microM). In the other two animals, the glutamate concentration remained unchanged. In conclusion, glutamate release in the retina does not proceed as rapidly as that in the cerebral cortex during 20 min of ischemia, and in fact decreases. This opposite trend shown by the two organs may be due to the slow depletion rate of ATP in the retina. This may explain the differing neuronal tolerance to ischemia in these two organs.
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PMID:Difference in glutamate release between retina and cerebral cortex following ischemia. 1067 56

The present study was undertaken to determine whether ATP-MgCl(2) administration in rats could protect hepatic mitochondrial function and improve energy metabolism during hepatic ischemia and subsequent reperfusion. Global hepatic ischemia was produced for 60 min followed by reperfusion. The rats then received 0.5 ml of saline or ATP-MgCl(2) intravenously. In saline-treated ischemic rats, serum alanine-aminotransferase levels peaked at 5 h. The aminotransferase level was significantly reduced in the ATP-MgCl(2) treatment group. The wet weight-to-dry weight ratio of the liver was significantly increased by ischemia/reperfusion. ATP-MgCl(2) treatment minimized the increase in this ratio. The ketone body ratio in blood, which reflects the mitochondrial free NAD(+)/NADH ratio, decreased after ischemia and at 1 h following reperfusion. This decrease was somewhat improved by ATP-MgCl(2) infusion. At 1 and 5 h after reperfusion, mitochondrial monoamine oxidase and glutamate dehydrogenase activities decreased. ATP-MgCl(2) infusion following ischemia restored the lost activities. Hepatic ATP levels in saline-treated rats were found to be 50% lower 5 h following reperfusion; however, treatment with ATP-MgCl(2) resulted in significantly higher ATP levels and energy charge. The accumulation of purine catabolites in ischemic tissues was reduced during reperfusion. ATP-MgCl(2) infusion resulted in accumulation of adenosine in reperfused liver. Mitochondrial lipid peroxidation was elevated in the saline-treated ischemic group, but this elevation was inhibited by ATP-MgCl(2) infusion. The present results lead us to conclude that the amelioration of liver function which occurs with ATP-MgCl(2) infusion following ischemia may be mediated through improvement in ischemia-induced mitochondrial energy metabolism.
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PMID:The beneficial effect of ATP-MgCl(2) on hepatic ischemia/reperfusion-induced mitochondrial dysfunction. 1097 26

Using a dialysis electrode, previous studies showed a clear biphasic release of glutamate during anoxia and ischemia. In this study, we examined two hypotheses: (1) glutamate is of vesicular origin and its release is thus Ca2+- and ATP-dependent in the first phase, while in the second phase glutamate is derived primarily from the metabolic pool, and (2) reversed glutamate uptake, due to electrogenic stoichiometry, produces the second phase during anoxic insult in the rat brain. A dialysis electrode continuously perfused with glutamate oxidase and ferrocene-conjugated bovine serum albumin (BSA) optimized the time resolution of monitoring, allowing quantitative oxygen-independent, real-time measurement of the extracellular glutamate concentration ([Glu]e) during anoxia. [Glu]e dynamics were analyzed during anoxia by combining the dialysis electrode with focal microinjection of substances inducing glutamate release. Following anoxia in the rat brain, a sharp and rapid [Glu]e elevation took place (first phase). The [Glu]e elevation then shifted, continuing a gently sloping rise throughout the anoxic period (second phase). This first phase disappeared with intracranial administration of either Co2+ or omega-conotoxin. The second phase rise increased with focal microinjection of KCl (300 mM, 1 microL) and decreased with NaCl (300 mM, 1 microL), ultimately reaching a plateau in both cases. Preloading with a novel glutamate transporter inhibitor (tPDC) decreased both the first and second phases of [Glu]e elevation. This dialysis electrode system provides data supporting in vivo evidence that the peak of the first phase of [Glu]e elevation is derived from the "neurotransmitter pool," while the second phase is derived from the neuronal and glial "metabolic pool," which is, at least, partly related to a "reversed uptake" mechanism in the anoxic rat brain.
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PMID:Oxygen-independent real-time monitoring of distinct biphasic glutamate release using dialysis electrode in rat striatum during anoxia: in vivo evaluation of glutamate release and reversed uptake. 1110 Dec 12

Reactive oxygen species generated by xanthine oxidase during reperfusion of ischemic liver might in part be responsible for ischemic organ injury. In normothermic ischemia/reperfusion rat model, we investigated whether allopurinol pretreatment improved ischemia-induced mitochondrial dysfunction. Rats were subjected to 60 min of hepatic ischemia and to 1 h and 5 h of reperfusion thereafter. At 18 h and 1 h before ischemia, the animals received 0.25 mL of either saline or allopurinol (50 mg/kg) i.p. In saline-treated ischemic rats, serum aspartate aminotransferase levels increased significantly at 5 h (4685 +/- 310 IU/L) and were significantly reduced with allopurinol pretreatment. Similarly, mitochondrial lipid peroxidation was elevated in the saline-treated ischemic group, but this elevation was prevented by allopurinol. In contrast, mitochondrial glutamate dehydrogenase activity and ketone body ratio decreased in the saline-treated group, but this decrease was also inhibited by allopurinol. Hepatic ATP levels in the saline-treated rats were 42% lower 5 h after reperfusion. However, treatment with allopurinol resulted in significantly higher ATP levels. Allopurinol treatment preserved the concentration of AMP in ischemic liver but inhibited the accumulation of xanthine in reperfused liver. Our findings suggest allopurinol protects against mitochondrial injury, which prevents a mitochondrial oxidant stress and lipid peroxidation and preserves the hepatic energy metabolism.
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PMID:Protective effect of allopurinol on hepatic energy metabolism in ischemic and reperfused rat liver. 1122 Jun 38

Ascorbate is highly concentrated in neuropils, and its extracellular release is closely related to that of the excitatory neurotransmitters. Thus, the extracellular release of ascorbate and glutamate was measured during the early stage of forebrain ischemia-reperfusion in the rat hippocampus using a microdialysis biosensor system. Male Wistar rats were anesthetized with halothane under mechanical ventilation and normothermia. Two probes of the microdialysis biosensor electrode were inserted in the hippocampus bilaterally. One probe was perfused with phosphate-buffered saline (PBS) and the oxidation signal of dialyzed ascorbate was recorded. A second electropolymerized probe was perfused with PBS containing glutamate oxidase for glutamate measurement. Forebrain ischemia-reperfusion was performed by bilateral carotid artery occlusion with hemorrhagic hypotension (MAP=30 mmHg) for 10 min (Group 10, n=10) or 15 min (Group 15, n=10), followed by reperfusion for 60 min. The release of glutamate increased significantly to 294% (Group 10) and 334% (Group 15) during ischemia, and then decreased rapidly. In Group 15, however, it remained significantly higher after reperfusion than in Group 10. The release of ascorbate increased significantly to 504% (Group 10) and 334% (Group 15) after reperfusion. In Group 10, it was significantly higher for 5-15 min after reperfusion than in Group 15. The marked increase of ascorbate during reperfusion was associated with the rapid decrease in glutamate. The extended time of ischemia significantly inhibited glutamate re-uptake and ascorbate release during reperfusion. These findings suggest the extracellular ascorbate release during reperfusion after global ischemia as a marker of glutamate re-uptake.
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PMID:Increased extracellular ascorbate release reflects glutamate re-uptake during the early stage of reperfusion after forebrain ischemia in rats. 1128 63

Our newly developed method using a dialysis electrode has made it possible to perform real time monitoring of extracellular glutamate concentration ([Glu]e) utilizing the oxygen-independent reaction with glutamate oxidase and ferrocene. In this study, we therefore, investigated [Glu]e changes during brain ischemia using both the conventional microdialysis method and the dialysis electrode method. A comparison between our newly developed dialysis electrode and conventional microdialysis methods provided the following results. When the conventional microdialysis method was employed: (1) the elevation of [Glu]e during complete global ischemia was delayed; and (2) the elevation of concentration and reuptake of glutamate were delayed during 10-min transient ischemia, and the elevation of [Glu]e reached a maximum later using conventional microdialysis than using our dialysis electrode. (3) The biphasic [Glu]e elevation of glutamate concentration detected using the dialysis electrode method was not observed using the conventional microdialysis method. It was additionally investigated why the conventional microdialysis method provides inferior time resolution. In this study, we also demonstrated with the chromatographic SMART procedure coupled to UV detection that biogenic substances, i.e. low molecular weight proteins and peptides, are released during ischemic injury, and they may cause a delay in the time resolution in the microdialysis method.
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PMID:Extracellular glutamate changes in rat striatum during ischemia determined by a novel dialysis electrode and conventional microdialysis. 1131 51


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