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)

Glucocorticoid hormones increase the activity of cytosolic aspartate aminotransferase (cAspAT) in the Fao rat hepatoma cell line. Maximal increase (6-10-fold) was observed 48 h following the addition of the glucocorticoid agonist dexamethasone at a concentration of 0.1 microM. The effect of dexamethasone was specific since it was not mimicked by sex steroids and was inhibited by the glucocorticoid antagonist RU 486. Insulin (0.1 microM) inhibited by more than 50% the induction of cAspAT by glucocorticoids. The cAMP analog, 8-bromoadenosine 3',5'-monophosphate (Br8cAMP, 0.5 mM), potentiated the effect of dexamethasone (2-3-fold) and partially relieved the inhibitory effect of insulin on the induction by dexamethasone. Both insulin and Br8-cAMP had no significant effect on basal activity. The mitochondrial isoenzyme was insensitive to the various hormonal treatments. Northern blot analysis revealed the presence of two major (2.1-kb and 1.8-kb) and one minor (4-kb) mRNA species hybridizing with a rat cAspAT probe. The regulation of these mRNAs by glucocorticoids, insulin and cAMP correlated with the variation of the cAspAT activity, suggesting that these hormones act at the pretranslational level. We compared the regulation of cAspAT mRNAs with those of tyrosine aminotransferase mRNA. Both were similarly increased by dexamethasone but the latter was also increased by cAMP even in the absence of the glucocorticoid agonist. In addition, the increase in tyrosine aminotransferase mRNA was inhibited by cycloheximide whereas the increase in cAspAT mRNAs was not. These results show that there are significant differences in the regulation of cAspAT and tyrosine aminotransferase by glucocorticoids and other hormones, although both enzymes probably contribute to the same metabolic pathway.
Eur J Biochem 1989 Dec 08
PMID:Regulation of cytosolic aspartate aminotransferase mRNAs in the Fao rat hepatoma cell line by dexamethasone, insulin and cyclic AMP. 255 14

A co-culture system of cerebellar granule cells (glutamatergic neurons) and hepatocytes has been developed. Petri dishes divided in halves by a temporary septum were coated with poly-L-lysine and cerebellar granule cells plated in one of the compartments. Five days later hepatocytes were plated in the other compartment and after 2 days the septum was removed and the two cell types shared the same culture medium for a period of 5 days. During this period of time cultures of neurons and hepatocytes kept separately or in co-culture exhibited identical characteristics with regard to activities of pyruvate kinase and glucokinase (hepatocytes), aspartate aminotransferase (neurons) as well as evoked transmitter release (neurons) and content of cytochrome P-450 (hepatocytes). The results show that it is possible to maintain neurons and hepatocytes in co-culture sharing the same culture medium for a prolonged period of time. Such a system may serve as a pharmacological model to study interactions between liver and brain cells with regard to neuroactive drugs.
Neurochem Res 1989 Dec
PMID:Characterization of a co-culture system of neurons and hepatocytes. 256 Aug 19

A data base was compiled containing the amino acid sequences of 12 aspartate aminotransferases and 11 other aminotransferases. A comparison of these sequences by a standard alignment method confirmed the previously reported homology of all aspartate aminotransferases and Escherichia coli tyrosine aminotransferase. However, no significant similarity between these proteins and any of the other aminotransferases was detected. A more rigorous analysis, focusing on short sequence segments rather than the total polypeptide chain, revealed that rat tyrosine aminotransferase and Saccharomyces cerevisiae and Escherichia coli histidinol-phosphate aminotransferase share several homologous sequence segments with aspartate aminotransferases. For comparison of the complete sequences, a multiple sequence editor was developed to display the whole set of amino acid sequences in parallel on a single work-sheet. The editor allows gaps in individual sequences or a set of sequences to be introduced and thus facilitates their parallel analysis and alignment. Several clusters of invariant residues at corresponding positions in the amino acid sequences became evident, clearly establishing that the cytosolic and the mitochondrial isoenzyme of vertebrate aspartate aminotransferase, E. coli aspartate aminotransferase, rat and E. coli tyrosine aminotransferase, and S. cerevisiae and E. coli histidinol-phosphate aminotransferase are homologous proteins. Only 12 amino acid residues out of a total of about 400 proved to be invariant in all sequences compared; they are either involved in the binding of pyridoxal 5'-phosphate and the substrate, or appear to be essential for the conformation of the enzymes.
Eur J Biochem 1989 Dec 08
PMID:Evolutionary relationships among aminotransferases. Tyrosine aminotransferase, histidinol-phosphate aminotransferase, and aspartate aminotransferase are homologous proteins. 257 69

The effects of silymarin (Legalon) therapy on liver function tests, serum procollagen III peptide level and liver histology were studied in 36 patients with chronic alcoholic liver disease in a six month double blind clinical trial. During silymarin treatment serum bilirubin, aspartate aminotransferase and alanin-aminotransferase values have been normalized, while gamma-glutamyl transferase activity and procollagen III peptid level decreased. The changes were significant, and there was a significant difference between post-treatment values of the two groups, as well. In the placebo group only gamma-glutamyl transferase values decreased significantly but to a lesser extent than that in the silymarin group. The histological alterations showed an improvement in the silymarin group, while remained unchanged in the placebo group. These results indicate that silymarin exerts hepatoprotective activity and is able to improve liver functions in alcoholic patients.
Orv Hetil 1989 Dec 17
PMID:[Liver-protective action of silymarin therapy in chronic alcoholic liver diseases]. 257 42

Activated macrophages convert L-arginine to citrulline and unstable nitrogen oxides that have cytotoxic properties. We recently have shown that the inhibition of protein synthesis in Kupffer cell (KC):hepatocyte (HC) coculture, following exposure to gram-negative bacterial endotoxin (lipopolysaccharide), is due to the metabolism of L-arginine by this cytotoxic pathway. Although this finding supports a role for activated KCs and the L-arginine-dependent mechanism in the HC dysfunction seen in sepsis, it and previous studies have failed to demonstrate direct damage to HCs by adjacent KCs. The current study was undertaken to determine if KCs exposed to lipopolysaccharide could directly damage HCs and, if so, whether the damage was dependent on the metabolism of L-arginine. By using the release of aspartate aminotransferase as a marker of HC damage, it was found that a significant aspartate aminotransferase release by KC:HC cocultures in response to lipopolysaccharide occurred only if L-arginine was present. In addition, requirements for significant aspartate aminotransferase release included KC:HC ratios of 7.5:1 or greater and L-arginine concentrations of 1 mmol or more. Although the KC-induced damage was mild, these results show that in vitro HC damage in KC:HC coculture does require the metabolism of L-arginine and supports a hypothesis that toxic L-arginine metabolites may contribute to liver cell damage in patients with sepsis.
Arch Surg 1989 Dec
PMID:Kupffer cell cytotoxicity to hepatocytes in coculture requires L-arginine. 258 66

Serum levels of F protein, a 44 kD cytoplasmic protein mainly found in hepatocytes, became elevated during episodes of graft dysfunction following orthotopic liver transplantation. In a study of 27 liver transplant recipients, the rise in F protein did not precede rises in the other conventional biochemical indices of hepatic dysfunction. Serum F protein concentration significantly correlated with serum levels of aspartate aminotransferase, gamma-glutamyltransferase, alkaline phosphatase, and bilirubin (all P less than 0.001) and also with the prothrombin time (P = 0.048). Despite its high concentration in liver cells, this marker does not provide any additional benefit in the diagnosis of graft dysfunction or in monitoring liver allograft function following transplantation.
Transplantation 1989 Dec
PMID:Serum F protein estimation in liver allograft recipients with graft dysfunction. 259 89

To determine if impaired intestinal absorption contributes to the folate deficiency observed in chronic alcoholics, we assessed in vivo folate absorption in Hanford mini-pigs fed ethanol with an adequate diet. Sixteen minipigs were pair-fed diets supplemented with ethanol or sucrose to 60% of total calories for 11 mo. In the ethanol-fed pigs peak blood alcohol concentrations averaged 28 mmol/L, serum alanine transaminase and aspartate transaminase activities were elevated, and liver histology showed a centrilobular distribution of succinate dehydrogenase. Tissue folate concentrations were comparable in both groups. The jejunal uptake of folic acid, measured by intestinal perfusion, was similar in both groups of animals and was not affected by acute exposure to 445 mmol/L ethanol. The in vivo hydrolysis of polyglutamyl folate was reduced by 35% in one ethanol-fed minipig. Decreased hydrolysis of polyglutamyl folate may represent an early step in the development of folate deficiency in chronic alcoholics.
Am J Clin Nutr 1989 Dec
PMID:Folate absorption in alcoholic pigs: in vivo intestinal perfusion studies. 259 32

The autonomic mechanisms of fasting-induced bradycardia of cattle were studied using heart rate spectral analysis. This was performed on digitized, lead II, surface electrocardiograms from conscious, fed, and 48-h-fasted adult cows. Fasting resulted in a significant (P less than 0.05) decrease in resting heart rate and a significant (P = 0.0041) increase in low frequency (0-90 mHz) power spectral area. Administration of atropine sulfate (0.02 mg/kg iv) in either the fed or fasted state resulted in a significant (P less than 0.001) decrease in both low-frequency and high-frequency (100-400 mHz) power spectral areas. Significant (P less than 0.05) increases in serum total bilirubin, inorganic phosphorus, and total protein were associated with fasting. Significant decreases were seen in fasting serum aspartate aminotransferase and potassium values. Manual evacuation of the rumen of seven steers with chronic rumen fistulae resulted in a mean percent decrease in heart rate of 22 +/- 0.9% (mean +/- SE). These results indicate that in normal cattle a decrease in ruminorecticular fill results in a reflex slowing of the heart rate, due predominantly to an increase in parasympathetic tone.
Am J Physiol 1989 Dec
PMID:Heart rate spectral analysis of fasting-induced bradycardia of cattle. 260 92

Forty-one patients with chronic hepatitis were divided into an HBe antigen-positive group (n = 13) and an HBe antigen-negative group (n = 28) to clarify the relationship between the presence of HBe antigen and liver function. In the HBe antigen-positive group, the activities of serum alanine aminotransferase (p less than 0.01), aspartate aminotransferase (p less than 0.05) and guanase (p less than 0.01) were significantly higher than those in the HBe antigen-negative group. The correlation coefficient between the HBe antigen titer and guanase activity was 0.528, which was higher than the corresponding values for alanine aminotransferase and aspartate aminotransferase. The determination of guanase activity in serum may be useful for evaluating the clinical severity of HBe antigen-positive chronic hepatitis.
Rinsho Byori 1989 Dec
PMID:[Activity of guanase in serum and liver function tests in HBe antigen-positive chronic hepatitis]. 261 68

The mechanisms of leakage of intracellular enzymes, and especially the cytosolic and mitochondrial isozymes of aspartate aminotransferase (AST), in ischemic rat liver were studied. On recirculation of ischemic liver, cytosolic AST (cAST) promptly appeared in the blood. Release of cytosolic enzymes, including cAST and lactic dehydrogenase, resulted from disruption of blebs that protruded from parenchymal cells into the sinusoidal space. When these blebs were formed in ischemic liver, mitochondria still remained in core regions of the injured cells and were not found in the blebs. Consistent with this fact, mitochondrial AST (mAST) did not leak into the circulation from ischemic liver until most of the cAST had leaked out. This delayed leakage of mitochondrial enzymes was also consistent with the fact that the mitochondrial membranes maintained a diffusion barrier against matrix enzymes even after anoxia for 2 h, when their oxidative phosphorylation capacity had been lost. These results indicate that mitochondrial enzymes are liberated into the blood only after appreciable disintegration of the cells, probably necrosis, and that the cumulative activity of mAST in the blood should reflect the extent of necrosis in ischemic organs better than that of cAST.
Clin Chim Acta 1989 Dec 15
PMID:Different patterns of leakage of cytosolic and mitochondrial enzymes. 262 Apr 58


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