Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P17174 (aspartate aminotransferase)
 14,872 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

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

The toxic and cellular metabolic effects of atractyloside, a diterpenoid glycoside, which causes fatal renal and hepatic necrosis in vivo in animals and humans, have been investigated in tissue slices prepared from male domestic pig kidney and liver. Precision-cut slices (200 microm thick) were incubated with atractyloside at concentrations of 200 microM, 500 microM, 1.0 mM and 2.0 mM for 3 h at 37 degrees C and changes in lipid profile and pyruvate-stimulated gluconeogenesis investigated. Lipid peroxidative changes, reduced glutathione (GSH) and ATP content, the release of lactate dehydrogenase (LDH), alkaline phosphatase (ALP), alanine and aspartate aminotransferase (ALT/AST) were also assessed. After 3 h of incubation, atractyloside caused a significant (P < 0.01) and concentration-dependent leakage of LDH and ALP from kidney slices. Only LDH leakage was significantly elevated in liver slices while ALT and AST leakage showed marginal increase. Atractyloside at concentrations of > or =200 microM caused a significant increase in lipid peroxidation, but only in liver slices. However, atractyloside at concentrations of > or =200 microM caused a marked depletion of GSH and ATP content in both kidney and liver slices. There was a marked decrease in total and individual phospholipid in kidney but not in liver slices. However, cholesterol and triacylglycerol levels were not affected by atractyloside in both kidney and liver slices. Renal and hepatic pyruvate-stimulated gluconeogenesis were significantly (P < 0.05) inhibited at atractyloside concentrations of > or =500 microM. Accumulation of organic anion p-amino-hippuric acid (PAH) was also inhibited in renal cortical slices at atractyloside concentrations of > or =500 microM. These results suggest that the observable in vivo effect of atractyloside can be reproduced in slices and that basic mechanistic differences exist in the mode of toxicity in liver and kidney tissues. The data also raise the possibility that the mechanistic basis of metabolic alterations in these tissues following treatment with atractyloside may be relevant to target selective toxicity.
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PMID:The toxic mechanism and metabolic effects of atractyloside in precision-cut pig kidney and liver slices. 976 68

The hepato-steatogenic compound ethionine has been used to investigate the correlations between in vivo and in vitro toxicity data. The aim was to find a suitable model of toxicity in hepatocyte suspensions or monolayers in vitro, which could predict the known toxicity of ethionine in vivo and which could be implemented in screening compounds of unknown toxicity. Thus a variety of markers of cytotoxicity, metabolic competence and liver-specific functions were investigated in rat hepatocyte suspensions and monolayers and compared with in vivo data in the rat. The following markers were measured in the appropriate system: (1) Neutral red uptake; 3-(4,5 dimethyl)thiazol-2-yl,-2,5-diphenyl tetrazolium bromide (MTT) reduction; lactate dehydrogenase (LDH), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) leakage (cytotoxicity). (2) ATP levels, protein synthesis and glutathione (GSH) levels (metabolic competence). (3) Urea and triglyceride synthesis and beta-oxidation (liver specific functions). Ethionine (0-30 mM) did not affect the markers of direct cytotoxicity, except neutral red uptake, which was reduced by 18 and 30 mM ethionine after 20 h in culture. ATP and GSH depletion occurred in hepatocyte suspensions at the highest concentrations of ethionine (20 and 30 mM) after 1 h. In monolayers, GSH levels were reduced after 4 h, but not 20 h. Urea synthesis was increased in hepatocyte suspensions from 1 to 3 h by 10-30 mM ethionine and reduced after 20 h in cultured hepatocytes (18-30 mM). Protein synthesis was reduced and beta-oxidation was increased in ethionine-treated hepatocyte suspensions. Unfortunately, there was no measurable effect on triglyceride accumulation within cells (the major biochemical change in vivo) in either system. Ethionine treated hepatocytes in suspension showed the same rate of triglyceride synthesis and transportation out of cells as control cells. Thus, hepatocyte suspensions were able to mimic the early biochemical effects of ethionine in vivo (ATP and GSH depletion, inhibition of protein synthesis) and some effects on urea synthesis, but monolayer cultures appeared to be less sensitive to the toxicity of ethionine. However, neither in vitro system was able to model the effects of ethionine on the accumulation of triglycerides in vivo.
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PMID:Ethionine toxicity in vitro: the correlation of data from rat hepatocyte suspensions and monolayers with in vivo observations. 980 31

Ischaemia-reperfusion induces structural and functional damage to hepatocytes. The purpose of this study was to evaluate the protective effect of trimetazidine, an anti- ischaemic drug, in a rat liver model of ischaemia-reperfusion. Male Wistar rats were divided into groups pretreated with different doses of trimetazidine (1, 5, 10 or 20 mg kg-1 day-1) or saline for 7 days. Liver ischaemia was induced for 120 min and blood reflow was subsequently restored for 30, 60, 90 or 120 min. The activities of alanine aminotransferase (ALAT) and aspartate aminotransferase (ASAT) as well as the bile flow and the liver ATP content were determined. Ischaemia-reperfusion induced major alterations of hepatic functions involving increases of ASAT and ALAT activities, a drop of ATP content and a sharp decrease in bile flow. Trimetazidine pretreatment reduced the liver injury. Indeed, it lowered the increase in ALAT and ASAT activities observed immediately after reperfusion and maintained higher concentrations of hepatic ATP. Simultaneously, bile flow was increased. These effects were dose-dependent and 5 mg kg-1 day-1 seemed to be the lowest effective dose. In this experimental model trimetazidine pretreatment reduced the liver damage induced by ischaemia-reperfusion. Our data suggest that trimetazidine may be a useful drug in liver surgery to prevent ischaemia-reperfusion injury.
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PMID:Trimetazidine ameliorates the hepatic injury associated with ischaemia-reperfusion in rats. 1009 46


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