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)

An unusual glucocorticoid-responsive element (called GRE A) was found to mediate the induction of the cytosolic aspartate aminotransferase gene by glucocorticoids and was bound by the glucocorticoid receptor in a DNase I footprinting assay. GRE A consists of two overlapping GREs, each comprising a conserved half-site and an imperfect half-site. The complete unit was able to confer glucocorticoid inducibility to a heterologous promoter (delta MTV-CAT). Mutation of any of the half-sites, including the imperfect ones, abolished inducibility by the hormone, demonstrating that each of the isolated GREs was inactive. In electrophoretic mobility shift assays, purified rat liver glucocorticoid receptor (GR) formed a low-mobility complex with GRE A, presumably containing a GR tetramer. When purified bacterially expressed DBD was used, low-mobility complexes as well as dimer and monomer complexes were formed. In inactive mutated oligonucleotides, no GR tetramer formation was detected. Modification of the imperfect half-sites in order to increase their affinity for GR gave a DNA sequence that bound a GR tetramer in a highly cooperative manner. This activated unit consisting of two overlapping consensus GREs mediated glucocorticoid induction with a higher efficiency than consensus GRE.
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PMID:A functional glucocorticoid-responsive unit composed of two overlapping inactive receptor-binding sites: evidence for formation of a receptor tetramer. 796 40

The nucleotide sequence of a 19,000 base pair region from the left arm of chromosome XI of Saccharomyces cerevisiae has been determined and analysed. It covers the HAP4-GFA1-LAP4 loci already described. As expected HAP4, GFA1 and LAP4 genes have been found and six new open reading frames (ORFs) with a coding capacity of more than 100 amino acid residues have been identified. One of them (YKL461) shows a high degree of identity with an aspartate aminotransferase gene. This raises the question of a second aspartate aminotransferase gene in yeast. A second ORF (YKL462) shows features compatible with a membranous localization. The other ORFs do not show a similarity with any known gene. A member of the highly repetitive 'CAT' DNA sequence is present.
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PMID:The DNA sequence analysis of the HAP4-LAP4 region on chromosome XI of Saccharomyces cerevisiae suggests the presence of a second aspartate aminotransferase gene in yeast. 810 75

The cytosolic aspartate aminotransferase (cAspAT) is a ubiquitous enzyme that displays liver-specific hormonal regulation. In the hepatoma cell line Fao, both the activity and the mRNA level of cAspAT are increased by glucocorticoids. This effect is potentiated by cAMP and inhibited by insulin. Using in vivo run-on experiments, we showed that these effectors act at the transcriptional level. A cAspAT gene fragment containing 2405 bp of the promoter was sequenced. Deletion fragments of this promoter were inserted upstream of the CAT gene, and the regulation of their activity was assayed following transfection in Fao cells. Stable transfection experiments established that the construct including the entire 2.405-kb fragment undergoes positive regulation by glucocorticoids and cAMP and negative regulation by insulin similar to the regulation of the endogenous gene. A physical separation of the positive and negative control elements is suggested by the fact that cAMP acted on the -682/-26-bp fragment (a 2-fold increase of the stimulation by dexamethasone), whereas the negative regulation by insulin (50% of the stimulation by dexamethasone) required the -1983/-1718-bp fragment. Both regions were required for maximal glucocorticoid activity (6-9-fold increase of CAT activity). We conclude that at least two regulatory regions, a proximal and a distal one, are required for full hormonal regulation of the cAspAT gene.
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PMID:Regulation of the cytosolic aspartate aminotransferase housekeeping gene promoter by glucocorticoids, cAMP, and insulin. 839 22

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

The safety of donor is the first priority during whole procedure in living donor liver transplantation. We evaluated the short-term results of partial living donor liver transplantation in the view of donor safety. We prospectively evaluated the extent of liver regeneration, the recovery of liver function, and the perioperative complications in 41 live liver donors for partial liver transplantation at our institution. We developed novel personal computer volumetry program for the evaluation of liver regeneration. Serial CAT scan was performed preoperatively, at postoperative day (POD) #7 and POD #30 and liver volume was measure by using volumetry program. The serum level of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin (T.bil.) was serially monitored. There were 34 males and 7 females. The mean preoperative liver volume was 1320.6 cm3. The remained mean liver volume was 687.8 cm3 after harvest, and increased to 954.4 cm3 (144.6%) at POD #7, and 1169.5 cm3 (81.4%) at POD #30, which was 88.5% of preoperative total liver volume. The serum level of ALT/ AST and T.bil. peaked at POD #1 and declined thereafter, and finally returned to preoperative level at POD #30. The regeneration rate was significantly different by age, type and size of graft according to the donors. Six donors experienced postoperative complications and they were four pleural effusions, one wound infection and one case of bile duct stenosis that was treated by endoscopic nasal biliary drainage. All of them were right lobe donors. In conclusion, the donor liver regenerated up to 88.5% of preoperative volume with full recovery of liver function at POD #30. Right lobe donors suffered more complications and need more meticulous operative and postoperative care than left lobe or left lateral segment donors.
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PMID:Postoperative liver regeneration and complication in live liver donor after partial hepatectomy for living donor liver transplantation. 1470 18

The aim of this study is to examine the relationship between alcohol dependence and oxidative status. The biochemical parameters and antioxidants status were measured among 28 patients with alcohol dependence. Nineteen healthy persons without drinking problem were recruited as the control subjects. The activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyltransferase (gamma-GT), and levels of cholesterol, triglyceride (TG), and uric acid were significantly increased in the specimen of patients compared with control. Serum malondialdehyde (MDA) levels of the patients were found to be significantly increased compared with controls and decreased after abstinence. Superoxide dismutase (SOD) and glutathione peroxidase (GPX) activities were, respectively, 86% and 37% lower in alcoholic patients. After 14 d of abstinence, SOD activity was significantly reduced by 85%, CAT by 52%, and GPX by 54%, whereas no change was found in activity of glutathione reductase (GR). The duration of alcohol dependence is significantly correlated with the levels of MDA. In addition, the activity of CAT was significantly correlated with MDA levels. The results of this study suggest that oxidative stress occurred during alcohol dependence and subsequently affected the antioxidants mechanisms.
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PMID:Oxidative status in patients with alcohol dependence: a clinical study in Taiwan. 1607 62

Penicillin and other antibiotics are routinely incorporated in insect culture media. Although culturing insects in the presence of antibiotics is a decades-old practice, antibiotics can exert deleterious influences on insects. In this article, we test the hypothesis that one of the effects of dietary penicillin is to increase oxidative stress on insects. The effects of penicillin on midgut concentrations of the oxidative stress indicator malondialdehyde (MDA) and on midgut antioxidant enzyme (superoxide dismutase [SOD], catalase [CAT], glutathione S-transferase [GST], and glutathione peroxidase [GPx]) and transaminases (alanine aminotransferase and aspartate aminotransferase) activities in greater wax moth, Galleria mellonella (L.), were investigated. The insects were reared from first instars on artificial diets containing 0.001, 0.01, 0.1, or 1.0 g penicillin per 100 g of diets. MDA content was significantly increased in the midgut tissues of each larval instar reared in the presence of high penicillin concentrations. Activities of antioxidant and transaminase enzymes did not show a consistent pattern with respect to penicillin concentrations in diet or age of larvae. Despite the increased penicillin-induced oxidative stress in gut tissue, antioxidant and transaminase enzymes did not correlate with oxidative stress level or between each other in larvae of other age stages except for the seventh instar. We found a significant negative correlation of MDA content with SOD and GST activities in seventh instars. SOD activity was also negatively correlated with CAT activity in seventh instars. These results suggest that exposure to dietary penicillin resulted in impaired enzymatic antioxidant defense capacity and metabolic functions in wax moth larval midgut tissues and that the resulting oxidative stress impacts midgut digestive physiology.
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PMID:Penicillin-induced oxidative stress: effects on antioxidative response of midgut tissues in instars of Galleria mellonella. 1797 30

Injection of D-galactosamine and lipopolysaccharide (DGaIN/LPS) is useful as an experimental model of acute hepatic damage. Juvenile rats were used for investigation. The hepatoprotective activity of aqueous garlic (Allium sativum) extract (AGE) at a dose of 300 mg/kg body weight for 14 days, intraperitoneal (i.p.) prior to the induction of DGalN/LPS, was investigated against DGalN/LPS-induced hepatitis in rats. DGalN/LPS (300 mg/kg body weight/30 microg/kg body weight, i.p.), induced hepatic damage that was manifested by a significant increase in the activities of marker enzymes [alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and gamma glutamyl transferase (gamma GT)], bilirubin, lipid peroxides (LPO), tumor necrosis factor (TNF-alpha) and myeloperoxidase (MPO) activity level in serum. Also, the lipid profile in serum and liver homogenate including total cholesterol, triglycerides, free fatty acids and phospholipids were significantly deteriorated. The antioxidant enzyme activities (superoxide dismutase, SOD; reduced glutathione, GSH; catalase, CAT and glutathione peroxidase, GPX) in liver homogenate were significantly decreased in the DGalN/LPS. Pretreatment of rats with AGE reversed these altered parameters near to normal control values. Results of this study revealed that AGE could afford a significant protection in the alleviation of DGalN/LPS-induced hepatic damage.
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PMID:Aqueous garlic extract attenuates hepatitis and oxidative stress induced by galactosamine/lipoploysaccharide in rats. 1857 Feb 25

Toxicokinetics (TK) is usually performed by measurement of the total drug concentrations in plasma. However, free drug concentrations in plasma are considered to correlate directly with toxicodynamics (TD). In the present study, to evaluate the applicability of TK/TD analysis based on free drug concentrations, we investigated the TK/TD of clofibrate, which binds to albumin with a higher ratio, using an albumin-deficient mutant strain, Nagase analbuminemia rats (NAR). TK, blood chemistry, histopathology, drug and fatty acid metabolizing enzymes and microarray analysis in the liver were examined after a 4-day oral administration of clofibrate. Compared to Sprague-Dawley (SD) rats, the parent strain of NAR, 4.1-fold higher AUC(0-24hr) based on free drug concentrations (3445 versus 844 microg.hr/ml) was observed in NAR when both rats showed the same level of AUC(0-24hr) based on the total drug concentrations (4436 versus 4237microg.hr/ml). Additionally, more severe hepatocellular hypertrophy, increase in aspartate transaminase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH), decrease in total cholesterol (T.CHO), phospholipid (PL), triglyceride (TG), and non-esterified fatty acid (NEFA), and increase in the mRNA levels of fatty acid metabolizing enzymes (FAOS, CAT, and CPT) were observed in NAR at the same dose. These results demonstrated that NAR developed more severe toxicities and pharmacological effects than SD rats correlating with the higher AUC of the free drug concentrations. The results also suggested that TK/TD analysis based on the free drug concentration is appropriate to interpret the relationship between exposure and toxicity in cases of protein binding saturation including protein decrease or species differences on protein binding, especially when drugs showing a higher protein binding ratio are dosed.
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PMID:Toxicokintic and toxicodynamic analysis of clofibrate based on free drug concentrations in nagase analbuminemia rats (NAR). 1867 Jan 66

Oxidative damage is involved in the pathogenesis of various hepatic injuries. In the present study the capacity of Commiphora berryi (Arn) Engl bark as an antioxidant to protect against CCl(4)-induced oxidative stress and hepatotoxicity in Albino Wistar rats was investigated. Intraperitoneal injection of CCl(4), administered twice a week, produced a marked elevation in the serum levels of aspartate transaminase, alanine transaminase, alkaline phosphatase and bilirubin. Histopathological analysis of the liver of CCl(4)-induced rats revealed marked liver cell necrosis with inflammatory collections that were conformed to increase in the levels of SOD, GPx and CAT. Daily oral administration of methanolic extract of C. berryi (Arn) Engl bark at 100 and 200mg/kg doses for 15 days produced a dose-dependent reduction in the serum levels of liver enzymes. Treatment with C. berryi normalized various biochemical parameters of oxidative stress and was compared with standard Silymarin. Therefore, the results of this study show that C. berryi (Arn) Engl bark can be proposed to protect the liver against CCl(4)-induced oxidative damage in rats, and the hepatoprotective effect might be correlated with its antioxidant and free radical scavenger effects.
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PMID:Hepatoprotective and antioxidant effects of Commiphora berryi (Arn) Engl bark extract against CCl(4)-induced oxidative damage in rats. 1869 29


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