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:2.6.1.1 (aspartate aminotransferase)
21,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We describe the effects of the neurotoxin 3-nitropropionic acid (3-NPA) on fatty acid oxidation in neonatal rat brain astrocytes in primary culture, using a sensitive assay for beta-oxidation which depends on the release of 3H2O from [9,10(n)-3H]palmitic acid. 3-NPA is a suicide inhibitor of succinate dehydrogenase, a constituent of both Krebs cycle and complex II of the mitochondrial respiratory chain. It is widely distributed in plants and fungi. Neurotoxicity of 3-NPA to humans and animals, leading to selective neuronal cell death, appears mediated by the reduced level of ATP induced by the toxin. We demonstrated that 3-NPA can also impair energy metabolism in astrocytes. Exposure of astroglial cells in culture to 3-NPA leads to inhibition of the release of 3H2O from [9,10(n)-3H]palmitic acid. Addition of 2 mM 3-NPA to the culture medium caused a rapid decrease in beta-oxidation activity, which reached a plateau after 90 min. This inhibition was concentration-dependent. Concentration as low as 0.05 mM for 5 h significantly decreased beta-oxidation activity (25% inhibition). Half-maximal inhibition was obtained after treatment with 0.5 mM 3-NPA, and 3 mM induced a maximal response (63% inhibition) 3-NPA is clearly a potent inhibitor of beta-oxidation activity. We also show that 3-NPA 3 mM inhibits partially complex II (succinate ubiquinone reductase) and aspartate aminotransferase by 60 and 49% after 4 h treatment respectively. It has been shown that fatty acid is the preferred substrate for energy production in cultured astrocytes from developing brain. As astrocytes may also provide substrates alternative for energy metabolism in neurons and oligodendrocytes, it is likely that the inhibition of beta-oxidation by 3-NPA may contribute significantly to the damage induced by this toxin in the central nervous system.
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PMID:Inhibition of fatty acid beta-oxidation in rat brain cultured astrocytes exposed to the neurotoxin 3-nitropropionic acid. 921 76

Skeletal muscle biopsies were performed on 12 healthy sedentary subjects and on 22 non-dyalized chronic renal failure patients (CRF) on a free diet and after overnight fasting. Parathormone, glucagon and insulin were determined at the same time of biopsies. CRF patients showed significantly low ATP and creatine phosphate levels. Regarding enzyme activities, a high hexokinase Vmax was found, while the pyruvate kinase activity was lower than in the control group. For the tricarboxylic acid cycle, citrate synthase, succinate dehydrogenase and malate dehydrogenase activities were higher; total NADH cytochrome c reductase activity was also high, while cytochrome oxidase activity was slightly lower. Both alanine aminotransferase and aspartate aminotransferase activities were considerably high in comparison with the control group. In conclusion, our study revealed a hypermetabolic TCA cycle, but impaired oxidative phosphorylation, which partly explained the reduced ATP concentration. Excessive protein intake and hormonal derangements may play a role in these metabolic changes.
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PMID:Altered muscle energy metabolism in post-absorptive patients with chronic renal failure. 924 94

Experiments were performed on eight subjects affected by peripheral arterial occlusive disease (PAOD) of the lower limbs. Each patient was submitted to Ecodoppler, angiography and the "Treadmill test". Two bioptic muscle of these patients. A sample was used for the spectrophotometric and spectrophotofluorimetric determinations of: glycogen, pyruvate, lactate, citrate, alpha-ketoglutarate, malate, aspartate, glutamate, AMP, ADP, ATP and creatine phosphate (CP). The other bioptic sample was used to determine the following enzyme activities: hexokinase, phosphofructokinase, pyruvate kinase, lactate dehydrogenase, citrate synthase, succinate dehydrogenase, malate dehydrogenase, total NADH cytochrome c reductase, cytochrome oxidase, aspartate aminotransferase and alanine aminotransferase. Patients showed an increase in lactate dehydrogenase, total NADH cytochrome c reductase and succinate dehydrogenase activities, a decrease in glycogen, ATP and CP concentrations. Telethermographic data showed patient muscle thermic emission quantitatively different from control group. The telethermographic test can be used as an additional diagnostic tool to determine and monitor the efficiency of a muscle undergoing metabolic failure.
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PMID:Instrumental and metabolic evaluation of patients affected by peripheral arterial occlusive disease (PAOD) following surgical revascularization surgery. 928 78

The aim of this study was to determine whether the administration of free radical antagonists, immediately before and during the early minutes of reperfusion, improves muscle survival 24 hr after a period of ischemia. Rabbit rectus femoris muscles were isolated, made ischemic for 3 1/2 hr and treated with either desferrioxamine (DFX), an Fe3+ chelator, superoxide dismutase and catalase (SOD & CAT), which quench superoxide and hydrogen peroxide, or allopurinol, an inhibitor of xanthine oxidase (XO). After 24 hr reperfusion, muscle viability (+/-s.e.m.), measured by the nitro blue tetrazolium (NBT) vital staining technique, was 41.6 +/- 11.3% for saline-treated ischemic controls, 30.6 +/- 7.6% for DFX-treated, 46.7 +/- 10.3% for SOD & CAT-treated, and 43.3 +/- 9.5% for allopurinol-treated muscles. None of the treated groups differed significantly from the ischemic control group. Tissue myeloperoxidase, ATP and reduced glutathione levels, and plasma lactate dehydrogenase (LDH) and aspartate transaminase (AST) levels were increased by ischemia and reperfusion in all groups, but the changes did not differ between the treatment groups. Levels of XO in the rabbit muscle were determined and found to be very low in both normal and postischemic muscle. As XO is the target enzyme of allopurinol, its absence provides a basis for the lack of effect of this agent. However, it is not clear why DFX and SOD & CAT had no protective effect.
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PMID:Influence of postischemic administration of oxyradical antagonists on ischemic injury to rabbit skeletal muscle. 939 70

Allopurinol has been reported to ameliorate the side effects in patients following shock wave lithotripsy (SWL); however, the mechanism has not been studied. We have examined the protective effect of allopurinol on Madin-Darby canine kidney (MDCK) cells after shock wave exposure (SWE) by determining the release of aspartate aminotransferase (ASAT) and lactate dehydrogenase (LD), and the resting cytosolic Ca2+ concentration ([Ca2+]i). In SWE-treated cells, the release of ASAT and LD increased immediately, but largely transiently, by approximately 23% and 5-fold over control, respectively. Within 1-6 h after SWE there was a gradual rise in the resting [Ca2+]i of 16-137% above control. Allopurinol did not affect the transient enzyme release but blocked the long-term rises in the resting [Ca2+]i. The transient changes in [Ca2+]i evoked by two hormones, ATP and bradykinin, and a drug that releases Ca2+ from internal Ca2+ stores, thapsigargin, were only slightly affected in allopurinol-treated cells. We conclude that the protection conferred by allopurinol on patients treated with SWL might involve a direct protection of the kidney cells by maintaining a normal resting [Ca2+]i.
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PMID:Allopurinol blocks shock-wave-induced rises in cytosolic calcium levels in MDCK cells. 944 53

Muscle ATP loss with exercise has implications both to the causes of fatigue and muscle damage. To study this at the single muscle fibre level, five trained thoroughbred horses performed consecutive 90 second gallops on an inclined treadmill followed by a final gallop to fatigue. Biopsies of the m. gluteus medius were taken at rest, post-exercise and during 24 hour recovery. Blood lactate was 20.0 mmol litre-1 or more, and plasma NH3 300-800 mumol litre-1, following the final gallop. Minimal changes occurred in the plasma markers, CK and AST. ATP loss with exercise was 32.2 (SD 12.2) per cent. Following exercise single fibre ATP contents showed a much broader distribution than at rest, with contents in some close to zero. Following five and 24 hour recovery, however, frequency distribution curves were close to those seen at rest. There was no difference in the ATP contents of types I, IIa and IIb at rest of with exercise or recovery. The results pointed to marked heterogeneity between individual fibres in their biochemical response with exercise, independent of fibre type.
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PMID:ATP loss with exercise in muscle fibres of the gluteus medius of the thoroughbred horse. 949 49

The isolated perfused rat liver model was used to assess graft viability after 24 h of cold preservation. Two solutions were compared for liver preservation: Belzer's original UW solution (high-K+ UW) and a solution containing the same components but with inverted concentrations of sodium and potassium (high-Na+ UW). During the 120 min of normothermic reperfusion, livers preserved in the high-Na+ UW solution released lower levels of creatine kinase-BB isoenzyme, transaminases (ALT and AST), and potassium than those preserved in the high-K+ UW solution. Bile flow and biliary excretion of indocyanine green increased when livers were preserved in the high-Na+ UW solution. We found no statistical differences for oxygen consumption and tissue ATP concentration. The results of this study support the concept that a high-Na+ UW solution is a more effective means of preserving rat livers, at least after 24 h of cold-storage and 120 min of reperfusion in the isolated perfused model, than the original high-K+ UW solution. Liver preservation in the high-Na+ UW solution reduces damage to sinusoidal endothelial and hepatocellular cells. The use of an extracellular-like Belzer cold storage solution eliminates potassium-related problems in cold preservation and subsequent normothermic reperfusion while keeping all the qualities of the original UW solution.
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PMID:High-Na+ low-K+ UW cold storage solution reduces reperfusion injuries of the rat liver graft. 963 53

Recent studies suggest a crucial role played by mitochondria in the pathogenesis of ischemia-reperfusion injury. This study was conducted to clarify the role of trimetazidine, a cellular anti-ischemic agent, on mitochondria isolated from rat liver subjected to 120-min normothermic ischemia followed by 30-min reperfusion. Rats were divided into groups, pretreated with different doses of trimetazidine (5, 10 and 20 mg/kg/day) or saline and subjected to the ischemia-reperfusion process; another group served as the sham-operated controls. Alanine aminotransferase and aspartate aminotransferase activities and hepatocyte ATP content, bile flow and mitochondrial functions were assessed. Ischemia-reperfusion caused membrane leakage from hepatocytes and a decrease in ATP content and in bile flow. These effects were well correlated with alterations in mitochondrial function, namely, decrease in ATP synthesis, NAD(P)H level and mitochondrial membrane potential and generation of mitochondrial permeability transition. The pretreatment of rats with trimetazidine prevented these ischemia-reperfusion deleterious effects at both the cellular and mitochondrial level in a dose-dependent manner. It is concluded that trimetazidine at an optimal dosage of 10 mg/kg/day protects mitochondria against the deleterious effects of ischemia-reperfusion. This protective effect appears to be the key factor through which this drug exerts its cytoprotective activity.
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PMID:Trimetazidine counteracts the hepatic injury associated with ischemia-reperfusion by preserving mitochondrial function. 965 37

Mitochondrial aspartate aminotransferase is inactivated irreversibly on heating. The inactivated protein aggregates, but aggregation is prevented by the presence of the chaperonin 60 from Escherichia coli (GroEL). The chaperonin increases the rate of thermal inactivation in the temperature range 55-65 degrees C but not at lower temperatures. It has previously been shown [Twomey and Doonan (1997) Biochim. Biophys. Acta 1342, 37-44] that the enzyme switches to a modified, but catalytically active, conformation at approx. 55-60 degrees C and the present results show that this conformation is recognized by and binds to GroEL. The thermally inactivated protein can be released from GroEL in an active form by the addition of chaperonin 10 from E. coli (GroES)/ATP, showing that inactivation is not the result of irreversible chemical changes. These results suggest that the irreversibility of thermal inactivation is due to the formation of an altered conformation with a high kinetic barrier to refolding rather than to any covalent changes. In the absence of chaperonin the unfolded molecules aggregate but this is a consequence, rather than the cause, of irreversible inactivation.
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PMID:Thermal inactivation and chaperonin-mediated renaturation of mitochondrial aspartate aminotransferase. 969 23

The decreased tolerance of steatotic livers to warm ischemia complicates liver surgery. The efficacy of heat shock preconditioning in steatotic livers to lessen ischemia-reperfusion injury was studied in rats. Steatotic liver was produced in Lewis rats with a choline-deficient diet. Rats with steatotic livers were divided into a heat shock preconditioned group (group HS) and a control group (group C). All rats received 45 min of hepatic warm ischemia. Survival rates and changes in biochemical and histological parameters were compared in both groups. Heat shock protein 72 (HSP72) was produced only in group HS. The 7-day survival of the rats after warm ischemic intervention was significantly better in group HS (13/15) than in group C (5/15) (P < 0.01). The concentration of ATP in liver tissue (n = 10, P < 0.01) and serum levels of aspartate aminotransferase (n = 10, P < 0.05), alanine aminotransferase (n = 10, P < 0.01), and lactic dehydrogenase (n = 10, P < 0.01) at 40 min reperfusion were also significantly better in group HS than in group C. Histological examination at 40 min reperfusion showed severe sinusoidal congestion, hepatocyte necrosis, and increased positivity to 4-hydroxy-2-nonenal-modified proteins in group C livers; these signs were markedly suppressed in group HS livers. The data indicate that heat shock preconditioning provides the steatotic rat liver with significant tolerance to warm ischemia-reperfusion injury.
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PMID:Heat shock preconditioning ameliorates liver injury following normothermic ischemia-reperfusion in steatotic rat livers. 973 39


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