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)

The liver has been judged relatively resistant to ischemia, but prolonged inflow occlusion at normothermic conditions can produce evidence of reversible or irreversible hepatocellular damage. Cytoprotective agents have been used both experimentally and clinically to afford extended viability of hepatocytes under reduced perfusion. One agent, prostaglandin E1, has been described clinically as effective in sustaining liver function under ischemic conditions. We have sought to verify this observation in an experimental model using prolonged normothermic inflow occlusion. Twenty miniature pigs were anesthetized and subjected to subtotal normothermic hepatic inflow occlusion (portal vein, hepatic artery, choledochal vessels) to allow for sufficient splanchnic decompression. Half of the animals received pretreatment with prostaglandin E1 (alprostadil) 500 micrograms intravenously. Inflow occlusion was maintained for 2 hours followed by reperfusion and killing 24 hours later. As a measure of functional preservation, the tissue adenine nucleotides adenosine monophosphate, diphosphate, and triphosphate (AMP, ADP, ATP) were measured in ischemic liver by freeze-clamping and high-performance liquid chromatography during occlusion and after reperfusion. Cytosolic enzyme determinations (aspartate transaminase, alanine transaminase, lactate dehydrogenase) were also made before occlusion and after reperfusion. As a possible indicator of cellular injury, blood ionized Ca++ was measured before inflow occlusion and after reperfusion. Although no difference was found in levels of AMP and ADP between prostaglandin E1 and control animals, ATP levels rose significantly higher during recovery in prostaglandin E1 animals at 60 minutes and 24 hours after reperfusion (13.97 +/- 1.29 and 13.60 +/- 0.91 mumoles/gm dry weight prostaglandin E1 vs. 9.25 +/- 0.97 and 9.80 +/- 0.85 mumoles/gm dry weight co control, P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effect of prostaglandin E1 on liver adenine nucleotides and cytoplasmic enzymes in a porcine model of normothermic hepatic ischemia. 759 Jun 75

Quinidine in vitro significantly reduced accumulation of TEA (tetraethyl ammonium) and PAH (p-amino hippurate) and inhibited oxygen consumption in renal cortical slices. Mitochondrial respiratory control index (RCI) and ADP/O ratio were decreased. Intraperitoneal administration of quinidine at 75 mg/kg twice a day for four days inhibited TEA transport in renal cortical slices and decreased oxygen consumption. Mitochondria showed a reduction in ADP/O ratio but no change in RCI. Serum biochemical measurements indicated a significant elevation in serum creatinine, alanine aminotransferase (ALT), and aspartate aminotransferase (AST).
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PMID:In vitro and in vivo effects of quinidine on the kidneys in Fischer-344 rats. 830 84

Reoxygenation of rat-liver mitochondria after anoxic incubation induced release of matrix proteins. As assessed by release of a matrix enzyme, it was proportional to the rate of H2O2 production. The release was not observed with low concentrations of extramitochondrial free Ca2+, indicating a Ca(2+)-dependent pathway. Phospholipase A2 was not involved in the reoxygenation injury, because non-esterified fatty acids did not increase on reoxygenation even when re-acylation was inhibited and because inhibitors of phospholipase A2 had little effect on enzyme release. Cyclosporin A, ATP, ADP and inhibitors of pyridine nucleotide oxidation had a protective effect, strongly suggesting involvement of so-called Ca(2+)-dependent permeability transition. Ca2+ was also released from reoxygenated mitochondria and inhibition of reuptake of released Ca2+ attenuated the enzyme release. Similar releases of aspartate aminotransferase and Ca2+ were observed with mitochondria in an oxygen radical-generating system, hypoxanthine and xanthine oxidase. In this system, lecithin-cardiolipin liposomes also released entrapped Ca2+ without disruption of the membrane. From these results, we conclude that during reoxygenation, Ca2+ release and subsequent reuptake induced permeability transition of mitochondria, resulting in reoxygenation injury.
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PMID:Ca(2+)-induced, phospholipase-independent injury during reoxygenation of anoxic mitochondria. 841 80

To better characterize the role of skeletal muscle in chronic heart failure we studied energetic charge, metabolites and enzyme activity in the energy production pathway. We selected 15 males with severe chronic heart failure (NYHA class III, stable clinical conditions and in normal nutritional status) and seven controls. Controls and patients were submitted to biopsy of the vastus lateralis muscle in resting and fasting conditions. Hormone profiles were also evaluated. Our results showed near normal ATP, ADP and AMP concentrations, but there were substantially more reductions in glycogen (46 +/- 5 vs 77 +/- 6 mumoles glycosidic units.g-1 fresh tissue) and creatine phosphate (5 +/- 1 vs 13 +/- 1 mumoles.g-1 fresh tissue) in patients than in controls. We also found a reduction in glycolytic activity (pyruvate kinase 1009 +/- 79 vs 1625 +/- 26 nmoles. min-1.mg protein-1), despite normal tricarboxylic acid cycle velocity, an increase in alanine amino-transferase (964 +/- 79 vs 425 +/- 34 nmoles. min-1.mg protein-1) and in aspartate aminotransferase (515 +/- 44 vs 291 +/- 56 nmoles.min-1.mg protein-1). An increase was also observed in total NADH cytochrome c reductase (128 +/- 14 vs 68 +/- 5 nmoles.min-1.mg protein-1), while cytochrome oxidase activity was normal. The cortisol/insulin ratio was slightly elevated (77 +/- 4 vs 32 +/- 12). In conclusion, normonutritive patients with severe heart failure show an imbalance in the energy production/utilization ratio. The impairment is probably due both to a decrease in production and an increase in consumption of energy owing to greater cellular workload and/or a hypercatabolic state.
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PMID:Biochemical analysis of muscle biopsy in overnight fasting patients with severe chronic heart failure. 892 17

The red blood cell metabolic parameters ATP, ADP, sigma AN, ATP/ADP, ATP/ATP, energy charge, PAD, 2,3-DPH, Pn were studied in 106 patients with generalized meningococcus infection (GMI) and meningitis of other etiology over their natural history. There was a typical adaptative red blood cell response that featured glycolytic stimulation on hypoxia that ran with impaired red blood cell energy metabolism (RBCEM), negative energy balance. It was the most pronounced at the peak of disease. RBCEM changes occurred in the presence of antioxidative disorders of red blood cells as lowered PAD levels. When early complications, such as shock, brain edema, death developed, there was a high incidence of signs of erythrocytic biochemical disadaptation. The RBCEM changes were associated with the magnitude of cytolysis, i.e. serum AST and AST/ALT levels. The significance of the metabolic changes found in the red blood cells in the pathogenesis and clinical picture of GMI and purulent meningitis is discussed in the paper.
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PMID:[Erythrocyte metabolism in meningococcal infection and purulent meningitis]. 899 64

The possibility of resuscitating livers after warm ischaemia has been recently suggested. The aim of the present investigation was to analyse the effects of anoxia on the morphology of hepatic cells, to determine whether these effects are reversible after providing a resuscitation period between warm ischaemia (WI) and cooling, and to study the behaviour of the resuscitated liver in the recipient organism. Ten female, Large-White pigs acted as donors for 10 recipient animals of the same kind who received an orthotopic liver graft. Recipients were divided into two groups depending on whether the livers they received had undergone a resuscitation period (Group I (n=5) where animal livers were subjected to 5 min warm ischaemia (WI) without resuscitation, and Group II (n=5) where the livers were subjected to 5 min WI followed by 5 min resuscitation). Morphological and ultrastructural studies of liver cells were performed using light and electron microscopy. ATP, ADP and AMP levels were determined in liver biopsies by high performance liquid chromatography (HPLC). Plasma AST and bilirubin levels in the two groups were compared 24 h after transplantation. After 5 min of anoxia, hepatocytes showed two morphological patterns in response to WI. Some were appreciably condensed with dark mitochondria, peroxisomes and some cytoplasmic vacuoles. Others showed electronlucent organelles, inflamed mitochondria with broken cristae and disorganized endoplasmic reticulum. Hepatocytes showed globular microvilli and bleb formation with migration towards the sinusoids. One hour after the revascularisation of the resuscitated livers, the hepatocytes showed nearly normal morphological characteristics. However, the hepatocytes of non-resuscitated organs continued to show alterations. Kupffer cells were activated in the livers of both experimental groups. Ultrastructural changes and total tissue adenine nucleotide (TAN) levels recovered completely in resuscitated livers soon after transplant. These results suggest that when short WI periods are followed by equivalent periods of resuscitation, the hepatocytes of transplanted livers recover from the effects of anoxia.
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PMID:A histopathological study of anoxic-resuscitated liver allografts. 904 50

Liver damage as a consequence of rhabdomyolysis (RM) has not been well established on clinical and experimental grounds. Hepatic dysfunction was then investigated in rats 24 h after induction of acute renal failure with glycerol. Forty male Wistar rats (220-270 g) were dehydrated for 24 h and were divided in two group: GI experimental group (n = 14)-50% glycerol was injected (10 ml/Kg, one-half of the dose in each hindlimb muscle) and GII control group (n = 26)-animals received injection of saline solution. Twenty-four hours after the glycerol or saline injection all the animals were killed. Serum urea, creatinine, transaminases (AST, ALT) and CK were measured and significantly high values were obtained in experimental animals. Arterial blood pressure was measured and remained within normal levels in both groups. Hepatocyte mitochondrial respiratory function was estimated polarographically with determination of oxygen consumption without ADP (Basal respiration-State 4) and in the presence of ADP (Activated respiration-State 3). In experimental group (GI) there was significant low values of oxygen consumption in state 3, decrease of respiratory control rate and in ADP/O ratio (p < 0.05). Histological studies of the liver revealed a periportal necrosis and centrilobular degeneration. These studies suggested that hepatic dysfunction is an additional complication of glycerol-induced rhabdomyolysis. The pathogenesis and clinical implications of these abnormalities are discussed.
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PMID:[Hepatic dysfunction in myoglobinuric acute renal failure (rhabdomyolysis)--experimental study in rats]. 923 96

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

We studied the alterations in the metabolism of liver mitochondria in rats with acute pancreatitis. Male Wistar rats were allocated to a control group (group I) and to five other groups corresponding to 2, 4, 12, 24 and 48 h after the induction of acute pancreatitis by the injection of 5% sodium taurocholate into the pancreatic duct. Sham-operated animals were submitted to the same surgical steps except for the induction of acute pancreatitis. Mitochondrial oxidation and phosphorylation were measured polarographically by determining oxygen consumption without ADP (basal respiration, state 4) and in the presence of ADP (activated respiration, state 3). Serum amylase, transaminases (ALT and AST) and protein were also determined. Ascitic fluid, contents of amylase, trypsin and total protein were also determined and arterial blood pressure was measured in all groups. In ascitic fluid, trypsin and amylase increased reaching a maximum at 2 and 4 h, respectively. Serum amylase increased at 2 h reaching a maximum at 4 h. Serum transaminase levels increased at 12 and 24 h. After 2 h (and also 4 h) there was an increase in state 4 respiration (45.65 +/- 1.79 vs 28.96 +/- 1.50) and a decrease in respiration control rate (3.53 +/- 0.09 vs 4.45 +/- 0.08) and in the ADP/O ratio (1.77 +/- 0.02 vs 1.91 +/- 0.01) compared to controls (P < 0.05). These results indicate a disruption of mitochondrial function, which recovered after 12 h. In the 48-h groups there was mitochondrial damage similar to that occurring in ischemic lesion. Beat-to-beat analysis (30 min) showed that arterial blood pressure remained normal up to 24 h (111 +/- 3 mmHg) while a significant decrease occurred in the 48-h group (91 +/- 4 mmHg). These data suggest biphasic damage in mitochondrial function in acute pancreatitis: an initial uncoupled phase, possibly secondary to enzyme activity, followed by a temporary recovery and then a late and final dysfunction, associated with arterial hypotension, possibly related to ischemic damage.
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PMID:Hepatic damage during acute pancreatitis in the rat. 936 23

The protective effect of O-(3-piperidino-2-hydroxy-1-propyl)nicotinic amidoxime (BGP-15) against ischemia-reperfusion-induced injury was studied in the Langendorff heart perfusion system. To understand the molecular mechanism of the cardioprotection, the effect of BGP-15 on ischemic-reperfusion-induced reactive oxygen species (ROS) formation, lipid peroxidation single-strand DNA break formation, NAD(+) catabolism, and endogenous ADP-ribosylation reactions were investigated. These studies showed that BGP-15 significantly decreased leakage of lactate dehydrogenase, creatine kinase, and aspartate aminotransferase in reperfused hearts, and reduced the rate of NAD(+) catabolism. In addition, BGP-15 dramatically decreased the ischemia-reperfusion-induced self-ADP-ribosylation of nuclear poly(ADP-ribose) polymerase(PARP) and the mono-ADP-ribosylation of an endoplasmic reticulum chaperone GRP78. These data raise the possibility that BGP-15 may have a direct inhibitory effect on PARP. This hypothesis was tested on isolated enzyme, and kinetic analysis showed a mixed-type (noncompetitive) inhibition with a K(i) = 57 +/- 6 microM. Furthermore, BGP-15 decreased levels of ROS, lipid peroxidation, and single-strand DNA breaks in reperfused hearts. These data suggest that PARP may be an important molecular target of BGP-15 and that BGP-15 decreases ROS levels and cell injury during ischemia-reperfusion in the heart by inhibiting PARP activity.
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PMID:BGP-15, a nicotinic amidoxime derivate protecting heart from ischemia reperfusion injury through modulation of poly(ADP-ribose) polymerase. 1069 58


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