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)

SPAAT (short piece of alpha 1-antitrypsin [AAT]), the 44-residue C-terminal peptide of AAT, was originally isolated from human placenta [Niemann et al. (1992): Matrix 12:233-241]. It was shown to be a competitive inhibitor of serine proteases [Niemann et al. (in press): Biochem Biophys Acta]. The binding of SPAAT to one or more proteins of the extracellular matrix (ECM) was initially suggested on the basis of its recovery from tissue residues following a series of extractions designed to remove easily solubilized proteins [Niemann et al. (1992): Matrix 12:233-241]. Our binding studies with the model ECMs, Matrigel and Amgel, suggested that SPAAT might be bound by a specific collagen type as well as one or more non-collagenous ECM proteins. Individual ECM components were screened for their ability to bind SPAAT. When the four commonly occurring fiber-forming collagens (types I, II, III, and V) were evaluated, type III was found to be preferred. In addition, although SPAAT bound to preformed type III collagen fibers in a concentration dependent fashion, it did not bind to type III collagen molecules undergoing fibril formation. This is consistent with a physiological mode of interaction between SPAAT and type III collagen in vivo. Of the non-collagenous ECM macromolecules (laminin-1, fibronectin, entactin, and heparan sulfate) tested, laminin-1 was preferred. The binding of radiolabelled SPAAT to type III collagen and laminin-1 was competitively inhibited by unlabelled SPAAT as well as an unrelated protein, human serum albumin (HSA), to establish binding specificity. The kinetics of the release of the bound radiolabelled SPAAT were also examined to substantiate the non-covalent and reversible nature of this association. These results support the view that susceptible proteins of the ECM may actually be coated with SPAAT in vivo, possibly affording protection against inappropriate protease digestion.
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PMID:Binding of SPAAT, the 44-residue C-terminal peptide of alpha 1-antitrypsin, to proteins of the extracellular matrix. 925 91

Down regulation of aryl sulfotransferase IV (AST IV) in promotion/progression of liver carcinogenesis by N-2-fluorenylacetamide (2-FAA) has been established. This study examined whether the C-9 oxidized metabolites of 2-FAA, which have recently been shown to promote diethylnitrosamine (DEN)-initiated liver carcinogenesis in male Sprague-Dawley rats, effect the above change. Hence, in DEN-initiated rats, the effects of promoting regimens of 9-OH-2-FAA or 9-oxo-2-FAA, 15 oral doses at 50 and 100 mumol/kg of body weight, were compared to those of 2-FAA at 50 mumol/kg of body weight and of the vehicle on the activity of N-hydroxy(OH)-2-FAA sulfotransferase (ST), an isozyme of AST IV and AST IV expression and distribution. Relative to the vehicle, treatment with the fluorenyl compounds led to decreased levels in hepatic N-OH-2-FAA ST activity and development of hepatic nodules and tumors which had still lower levels of the ST activity than the respective remnant livers. At approximately 8 months after treatment with the C-9-oxidized compounds at doses twice that of 2-FAA, the extents of decreases in the hepatic N-OH-2-FAA ST activity and cytosolic AST IV protein in tumors were comparable to those with 2-FAA. Immunocytochemical analysis showed close association of AST IV deficiency with neoplastic liver lesions. In comparison to N-OH-2-FAA, 9-OH-2-FAA had only low and 9-oxo-2-FAA lacked sulfate acceptor activity in the presence of male rat liver cytosol or AST IV. At 3.3-fold greater concentration than N-OH-2-FAA, 9-oxo-2-FAA inhibited (27%) the sulfate acceptor activity of N-OH-2-FAA in the presence of AST IV, which suggested interference by 9-oxo-2-FAA at the active site. Although the C-9-oxidized compounds do not appear to be substrates for N-OH-2-FAA ST, their ability to cause a decrease in N-OH-2-FAA ST activity and protein similar to that of 2-FAA supports their role in hepatocarcinogenesis. Whereas 9-OH-2-FAA had a 3.9-fold greater sulfate acceptor activity in the presence of female than male rat liver cytosol and inhibited dehydroepiandrosterone ST activity of female rat liver, N-OH-2-FAA and 9-oxo-2-FAA inhibited estrone ST activity of male rat liver, suggesting that the C-9-oxidized compounds as well as N-OH-2-FAA are substrates for STs other than AST IV.
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PMID:Aryl sulfotransferase IV deficiency in rat liver carcinogenesis initiated with diethylnitrosamine and promoted with N-2-fluorenylacetamide or its C-9-oxidized metabolites. 931 85

We have recently demonstrated that indoxyl sulfate promotes the progression of glomerular sclerosis in uremic rats. In the present study, we determined whether an oral adsorbent (AST-120) could reduce the serum and urine levels of indoxyl sulfate and suppress the progression of chronic renal failure (CRF) in undialyzed uremic patients. Twenty-five undialyzed uremic patients were given AST-120 at a dose of 6 g/day for 6 months, while 10 undialyzed uremic patients were not given AST-120. The effects of the oral adsorbent on the slope of the 1/serum creatinine (Scr)-time plot, and the serum and urine levels of indoxyl sulfate were evaluated. Administration of AST-120 significantly decreased the serum and urine levels of indoxyl sulfate, and tended to improve the slope of the 1/SCr-time plot in the CRF patients. Among the patients in whom urinary excretion of indoxyl sulfate was reduced by AST-120, the oral adsorbent significantly improved the slope of the 1/SCr-time plot. The change in the slope of the 1/SCr-time plot showed a significant negative correlation with the change in the urine level of indoxyl sulfate. Thus, patients who showed a greater decrease of urinary indoxyl sulfate also showed more marked suppression of the progression of CRF. These results support the notion that indoxyl sulfate, a protein metabolite, is involved in the progression of CRF, and that an oral adsorbent can delay progression at least partly by reducing the serum and urine levels of indoxyl sulfate.
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PMID:The protein metabolite hypothesis, a model for the progression of renal failure: an oral adsorbent lowers indoxyl sulfate levels in undialyzed uremic patients. 935 Jun 73

We have previously demonstrated that indoxyl sulfate is a stimulating factor for the progression of glomerular sclerosis in uremic rats. In this study we determined if a low-protein diet or oral sorbent (AST-120) could reduce the serum and urine levels of indoxyl sulfate in 5/6-nephrectomized uremic rats and undialyzed uremic patients. The uremic rats were treated by fasting or AST-120 for 2 days. The serum and urine levels of indoxyl sulfate dramatically decreased 1-2 days after fasting or AST-120 treatment. We then measured the serum and urine levels of indoxyl sulfate and calculated protein intake from urinary amounts of urea nitrogen using Maroni's equation in 80 undialyzed uremic patients with creatinine clearance less than 30 ml/min. The serum and urine levels of indoxyl sulfate were significantly lower in the patients on a low-protein diet than in those in the normal-protein diet group. Administration of AST-120 significantly decreased serum and urine levels of indoxyl sulfate in 22 undialyzed uremic patients. In conclusion, a low-protein diet or AST-120 reduced the serum and urine levels of indoxyl sulfate, a stimulating factor for glomerular sclerosis, in both uremic rats and undialyzed uremic patients.
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PMID:Indoxyl sulfate and progression of renal failure: effects of a low-protein diet and oral sorbent on indoxyl sulfate production in uremic rats and undialyzed uremic patients. 938 12

This prospective, randomized controlled study was designed to examine the effects of oral adsorbent AST-120 on the progression of chronic renal failure (CRF) in patients on a strict low protein diet (LPD). Twenty-six patients with CRF (serum creatinine 3.0 to 8.6 mg/dl) on a LPD were randomly assigned to a control group (N = 13) or an AST-120 group (N = 13). The 1/Cr slope and creatinine clearance (CCr) slope were used to estimate the progression rate of CRF; uremic toxins, serum and urinary indoxyl sulfate (IS), peak 2a and guanidino substrates (GS) measured by HPLC. Comparisons were made between the baseline observation period for 6 to 12 months and the treatment period (0.6 g/kg/day of LPD alone or concurrent with 6 g/day of AST-120, for the control and the AST-120 groups, respectively) for 12 to 24 months in both groups. Both the 1/Cr slope and CCr slope were significantly lessened in the treatment period only in the AST-120 group. Serum and urinary IS, but neither peak 2a nor GS were significantly decreased in the treatment period only in the AST-120 group. We conclude that AST-120 administration concurrent with LPD may be superior to LPD alone in retarding the progression of CRF by inhibiting accumulation of indoxyl sulfate.
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PMID:Effects of oral adsorbent AST-120 on the progression of chronic renal failure: a randomized controlled study. 940 55

Copper sulfate is one of the most widely used algicides for the control of phytoplankton in lakes, reservoirs, and ponds. It is also used for aquatic weed control. To study the toxic effects of copper on carp (Cyprinus carpio L.), toxicity tests were carried out. Fish recovery in copper-free water was followed. After a 14-day period of exposure to five concentrations of copper sulfate (0.25-4.0 mg/L CuSO4, values ranging from approximately 5 to 70% of the 96-h LC-50) and a recovery period of the same duration, activities of the functional enzymes alkaline phosphatase (AP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) in the blood serum and gills were determined. Because the gills are the known target organ for copper, changes in gill structure were investigated as well. In all exposure groups for all the enzymes studied, an increase in activity was noted after 14 days. The increase in AP activity was the most pronounced in both gills and serum of carp exposed to the highest concentration tested (4 mg/L). After a "recovery" period, compared with the end of treatment, a decrease in enzyme activities was recorded, indicating eventual recovery from the Cu-induced stress (the only exception being the ALT activity in gills in the highest CuSO4 concentration). The results of biochemical analysis were confirmed by histopathology. Lesions such as epithelial hyperplasia, curling of secondary lamellae, and changes in chloride cells were observed on the gills, and their severity increased with increased toxicant concentration. Most of the changes were reversible, as exhibited by gill histopathology after the recovery period.
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PMID:Functional enzymes activity and gill histology of carp after copper sulfate exposure and recovery. 962 35

Temporal variation in metabolism and hepatotoxicity of acetaminophen (APAP) was examined using male ICR mice. Animals were injected with a single dose of APAP (400 mg/kg, i.p.) at 08:00, 14:00 or 20:00 h. APAP at this dose was markedly hepatotoxic to mice when administered at 20:00 h as determined by increases in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, and by decreases in hepatic glucose-6-phosphatase (G-6-Pase) activity. However, mice appeared to be entirely insensitive to an identical dose of APAP given either at 08:00 or 14:00 h. Hepatic glutathione (GSH) level was significantly higher at 08:00, but no difference in GSH levels between 14:00 and 20:00 h was observed in normal mice. APAP and its metabolites in blood were monitored using HPLC for 3 h following the treatment. There were no significant differences in the plasma concentrations of APAP, APAP-glucuronide, APAP-sulfate, or APAP-mercapturate among the mice treated with this drug at 08:00, 14:00 or 20:00 h. However, the APAP-cysteine and APAP-GSH levels measured at 1 h following the APAP treatment were significantly lower in mice treated with this analgesic either at 14:00 or 20:00 h. In vitro hepatic microsomal p-nitrophenol hydroxylase activities were not different between 08:00, 14:00 and 20:00 h. But ethoxyresorufin O-deethylase and aminopyrine N-demethylase activities measured at 14:00 h were significantly lower than those of 08:00 or 20:00 h. Thus, the greater hepatotoxicity of APAP administered at 20:00 h appears to be related to the marked decrease in hepatic GSH at this time period, whereas the simultaneous reduction in APAP activation may be responsible for the lack of hepatotoxicity in mice treated with this analgesic at 14:00 h. These results suggest that the temporal variation in hepatotoxicity and metabolism of APAP is determined by interactions of multiple factors including the hepatic GSH level and drug metabolizing activities.
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PMID:Temporal variation in hepatotoxicity and metabolism of acetaminophen in mice. 970 5

We recently demonstrated that indoxyl sulfate is a stimulating factor for the progression of chronic renal failure (CRF). In this study we determined whether the urine or serum levels of indoxyl sulfate are related to the progression rate of CRF in undialyzed uremic patients. Fifty-five CRF patients with a serum creatinine of >2 mg/dl who had not been treated with an oral sorbent (AST-120) were randomly enrolled in the study. We measured the serum and urine levels of indoxyl sulfate, and estimated the recent progression rate of CRF as the slope of the reciprocal serum creatinine versus time (1/S-Cr-time) plot. The mean urinary amount of indoxyl sulfate in the patients was 60 mg/day. Those with indoxyl sulfate urine levels of >60 mg/day had a significantly faster progression rate of CRF than those with <60 mg/day. Especially, those patients with indoxyl sulfate urine levels of >90 mg/day had the highest CRF progression rate and those with indoxyl sulfate urine levels of <30 mg/day had the slowest CRF progression rate. Urinary indoxyl sulfate had a significantly negative correlation with the slope of the 1/S-Cr-time plot. However, the serum level of indoxyl sulfate or the ratio of serum indoxyl sulfate to creatinine was not significantly correlated with the slope of the 1/S-Cr-time plot. In conclusion, high urine levels of indoxyl sulfate are related with a rapid progression of CRF in undialyzed uremic patients. Thus, urinary indoxyl sulfate is one of the clinical factors that affect CRF progression.
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PMID:Urinary indoxyl sulfate is a clinical factor that affects the progression of renal failure. 1020 73

An 82-year-old male patient was admitted for liver dysfunction. Laboratory test showed the following data; aspartate aminotransferase (AST) 79 IU/l, alanine aminotransferase (ALT) 28 IU/l, total bilirubin (T. Bil) 0.9 U, zinc sulfate turbidity test (ZTT) 48.9 U, gamma-globulin 4.9 g/dl, immunoglobulin G (IgG) 5,046 mg/dl, anti-nuclear antibodies x 320, anti-mitochondrial antibodies (-), hepatitis B virus surface antigen (HBsAg) (-), HBcAb (-), anti-hepatitis C virus (anti-HCV) (-), hepatitis C virus (HCV-RNA) (-), anti-hepatitis G virus (anti-HGV) (-), alpha-fetoprotein 306.8 ng/ml, carcinoembryonic antigen (CEA) 2.3 ng/ml, carbohydrate antigen (CA) 19-9 77.2 U/ml. Abdominal ultrasonography and computed tomography showed a large mass occupying most of the right lobe and portal thrombosis in the liver. Liver biopsy revealed cirrhosis with inactive hepatitis in the nontumorous lesion and well-differentiated hepatocellular carcinoma in the tumorous lesion. We report a rare case of an aged male patient with autoimmune hepatitis complicated by hepatocellular carcinoma.
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PMID:An aged male patient with autoimmune hepatitis complicated by hepatocellular carcinoma. 1039 80

In this work we investigate the possible toxicity of vanadyl sulfate (VOSO4), a compound capable of reducing hyperglycemia, on the following serum enzymes of diabetic young rats: alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LD) and creatine kinase (CK), as well as its effects on serum lipids. We find that at a concentration of 1 mg/mL VOSO4 has no toxic effect on the liver and muscles of diabetics young rats. These findings suggest that VOSO4 may be an alternative to insulin in the near future, due to its low cost, low toxicity and ready availability.
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PMID:Effect of oral vanadyl sulfate treatment on serum enzymes and lipids of streptozotocin-diabetic young rats. 1049 91


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