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)

Carbon tetrachloride feeding (3.2g/kg/72hr) for one month increased significantly the serum and tissue lipid profile and deranged the enzyme levels viz; alkaline phosphatase, alanine transaminase, aspartate transaminase, glutathionze reductase, HMGCoA reductase, catalase, gluc.6.PDH and malic enzyme in rats. Simultaneously the lipid peroxidation level in liver was also raised. On administration of garlic oil and its major nonpolar fraction (NPFGO) and a flavonoid isolated from the bark of Ficus bengalensis Linn, viz; leucopelargonin derivative respectively to different groups(100mg/kg/day) the deleterious effects of CCl4 were significantly ameliorated. The liver damage by CCl4 was satisfactorily prevented by these samples as effectively as Vit. E (50 mg/kg/day). The results prove that important nutraceuticals (phytonutrients) like bioflavonoids and theols i.e. allylic sulphide rich fractions give protection from toxins like CCl4. The order of beneficial effects of the drugs are Leucopelargonin > NPFGO > Garlic oil and their effects are comparable to that of vitamin E used at a minimal dose.
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PMID:Nutraceutical effects of garlic oil, its nonpolar fraction and a Ficus flavonoid as compared to vitamin E in CCl4 induced liver damage in rats. 1590 Sep 9

The present study was designed to evaluate the preventive effect of S-allyl cysteine sulfoxide (SACS) in isoproterenol (ISO)-induced myocardial ischaemia in male Wistar rats. Rats were pretreated with SACS (40 and 80 mg kg(-1) body-weight) for 5 weeks. After the treatment period, ISO (150 mg kg(-1) body-weight) was administered subcutaneously to rats at intervals of 24 h for 2 days. The activities of creatine kinase, creatine kinase-MB, lactate dehydrogenase, aspartate transaminase and alanine transferase were significantly increased in serum and significantly decreased in the hearts of ISO-treated rats. Pretreatment with SACS decreased the activities of these enzymes significantly in serum and significantly increased the activities in heart in ISO-treated rats. The levels of cholesterol, triglycerides and free fatty acids increased in serum and heart, while the levels of phospholipids increased in serum and decreased in heart in ISO-treated rats. SACS pretreatment showed a significant effect on the lipids studied. The activity of 3-hydroxy 3-methyl glutaryl coenzyme A (HMG CoA) reductase was significantly increased and the activity of lecithin cholesterol acyl transferase (LCAT) was significantly reduced in ISO-induced rats. Oral pretreatment with SACS significantly decreased the activity of HMG CoA reductase and significantly increased the activity of LCAT in ISO-induced rats. The levels of plasma thiobarbituric acid reactive substances and hydroperoxides were increased in ISO-treated rats. Pretreatment with SACS significantly decreased the levels of lipidperoxides in ISO-treated rats. The effect at a dose of 80 mg kg(-1) body-weight was more effective than at a dose of 40 mg kg(-1) body-weight and brought back all the biochemical parameters to near normal levels. Thus our study shows that SACS has a lipid-lowering effect in ISO-induced rats. Our study may have clinical relevance.
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PMID:Preventive effect of S-allyl cysteine sulfoxide (alliin) on cardiac marker enzymes and lipids in isoproterenol-induced myocardial injury. 1664 Aug 30

Propolis, a natural beehive product has been known for centuries for a variety of beneficial traditional medicinal properties. The present study was conducted to ascertain the antineoplastic potential of propolis along with paclitaxel against experimental mammary carcinogenesis. Female Sprague Dawley rats at 55 days of age were treated with dimethylbenz(a)anthracene to induce breast cancer. Paclitaxel at a dose of 33 mg/kg body mass intraperitoneally and propolis 50 mg/kg body weight orally was administered to the experimental animals, immediately after the carcinogen treatment and continued until the termination of the study. At the end of the treatment activities of phase I and II xenobiotic metabolizing enzymes and liver marker enzymes were measured. A significant increase in carcinogen activating enzymes, cytochrome P(450), cytochrome b(5) and NADPH cytochrome C reductase with concomitant decrease in phase II enzymes, glutathione transferase and UDP-glucuronyl transferase were observed in animals with mammary cancer. Furthermore there was a significant decrease in alanine aminotransferase, aspartate aminotransferase with a sharp increase in alkaline phosphatase, acid phosphatase and 5' nucleotidase. Propolis treatment caused the activity of these enzymes return to almost normal control levels, indicating the protective effect of propolis against dimethyl benz(a) anthracene induced carcinogenesis. On the basis of the observed results propolis can be considered a promising chemotherapeutic agent and can be administered as an adjuvant with paclitaxel chemotherapy.
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PMID:Therapeutic effect of propolis and paclitaxel on hepatic phase I and II enzymes and marker enzymes in dimethylbenz(a)anthracene-induced breast cancer in female rats. 1672 Jan 5

Central core disease is a nonprogressive or slowly progressive congenital myopathy with a variable degree of hypotonia and axial and proximal muscle weakness that is histologically characterized by areas devoid of oxidative enzyme activity, resulting from an absence or low numbers of mitochondria in these regions (central core). A 10-month-old, male, pony foal was examined because of stiff gait, marked contractures of the distal portion of the limbs, flexion deformities of the hooves, and moderate hypotonia that had been present from birth. The foal had increased creatine kinase (282 U/liter; reference interval 10-135 U/liter), lactate dehydrogenase (1,188 U/liter; reference interval 150-450 U/liter), and aspartate transaminase (377 U/liter; reference interval <290 U/liter) activities, suggesting muscle disease. Muscle biopsy was performed. In cytochrome oxidase-, succinate dehydrogenase-, and reduced nicotinamide adenine dinucleotide tetrazolium reductase-reacted sections, the dominant morphologic feature was the absence of oxidative enzyme activity in the cores. By use of immunohistochemical technique with a monoclonal antibody against desmin, the cores were clearly delineated and a desmin network was present within the cores. Ultrastructurally, the core areas were characterized by preserved sarcomeres with irregular Z-lines, with some streaming or zigzag appearance and abnormal sarcoplasmic reticulum profiles and T-tubules. Lack of mitochrondria within central cores was observed. Diagnosis of myopathy with central cores was made.
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PMID:Myopathy with central cores in a foal. 1684 6

The effects of cadmium stress on growth, morphology, and protein expression were investigated in Rhodobacter capsulatus B10 using two-dimensional polyacrylamide gel electrophoresis and a scanning electron microscope with an energy dispersive X-ray spectrometer. The bacterium grew in the presence of 150 microM CdCl2 and highly induced heat-shock proteins (GroEL and Dnak), S-adenosylmethionine synthetase, ribosomal protein S1, aspartate aminotransferase, and phosphoglycerate kinase. Interestingly, the ribosomal protein S1 was proportionally expressed as the amount of cadmium in the medium, suggesting that S1 may be required for the repair of cadmium-mediated cellular damage. On the other hand, we identified five cadmium-binding proteins: 2-methylcitrate dehydratase, phosphate periplasmic binding protein, inosine-5'-monophosphate dehydrogenase/guanosine-5'-monophosphate reductase, inositol monophosphatase, and lytic murein transglycosylase. The cadmium-treated cells had a filamentous structure and contained less phosphorous than the untreated cells. We propose that these characteristics of the cadmium-treated cells may be due to the inactivation of the phosphate periplasmic binding protein and lytic murein transglycosylase by cadmium.
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PMID:Effects of cadmium stress on growth, morphology, and protein expression in Rhodobacter capsulatus B10. 1703 Oct 48

Inhibitors of 3-hydroxy-3methylglutarly coenzyme A, reductase, namely statins, exert pleiotropic actions beyond lipid-lowering effects. In ex vivo and in vitro studies, statins have antioxidative and antiinflammatory effects. Herein, we sought to determine whether treatment with fluvastatin (FV) would be beneficial in a rat model of common bile duct ligation (BDL)-induced liver injury. Female rats were subjected to a sham (n=10) or BDL (n=20). Obstructive jaundice was induced in rats by the ligation and division of the common bile duct. Three days after operation, rats subjected to CBDL were randomized to receive treatment with either FV (10 mg/kg) or saline every day over a 10 days experimental period. High levels of alanine aminotransferase, aspartate aminotransferase, and gamma glutamyltransferase decreased significantly (P<0.05) in animals treated with FV with compared to saline-administrated BDL animals. Compared with sham-operated rats, CBDL rats showed significantly higher levels of total nitrite and nitrate, malondihaldehyde, tumor necrosis factor alpha, myeloperoxidase, and lower concentrations of glutathione, superoxide dismutase, and catalase in the liver tissue (P<0.001). All of these changes were significantly attenuated (P<0.05) by treatment with FV after CBDL. CBDL was associated with increased apoptosis and nuclear factor kappa beta expression in saline-treated rats. Treatment with FV also decreased these parameters. These data support the view that FV ameliorates hepatic inflammation, lipid peroxidation, and tissue injury in rats subjected to CDBL. FV warrants further evaluation as an adjunctive treatment to ameliorate liver injury from extrahepatic biliary obstruction.
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PMID:Fluvastatin reduced liver injury in rat model of extrahepatic cholestasis. 1708 24

The present study investigates the hepatoprotective effect of fenugreek seed polyphenolic extract (FPEt) against ethanol-induced hepatic injury and apoptosis in rats. Chronic ethanol administration (6 g/kg/day x 60 days) caused liver damage that was manifested by the elevation of markers of liver dysfunction--aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), bilirubin and gamma-glutamyl transferase (GGT) in plasma and reduction in liver glycogen. The effects on alcohol metabolizing enzymes such as alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) were studied and found to be altered in the alcohol-treated group. Ethanol administration resulted in adaptive induction of the activities of cytochrome p450 (cyt-p-450) and cytochrome-b5 (cyt-b5) and reduction in cytochrome-c-reductase (cyt-c-red) and glutathione-S-tranferase (GST), a phase II enzyme. Further, ethanol reduced the viability of isolated hepatocytes (ex vivo) as assessed by the trypan blue exclusion test and increased hepatocyte apoptosis as assessed by propidium iodide staining (PI). Treatment with FPEt restored the levels of markers of liver injury and mitigated the alterations in alcohol metabolizing and detoxification enzymes and the electron transport component cytochrome-c reductase. Increased hepatocyte viability and reduced apoptotic nuclei were observed in FPEt-treated rats. These findings demonstrate that FPEt acts as a protective agent against ethanol-induced abnormalities in the liver. The effects of FPEt are comparable with those of a known hepatoprotective agent, silymarin.
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PMID:Fenugreek (Trigonella foenum graecum) seed polyphenols protect liver from alcohol toxicity: a role on hepatic detoxification system and apoptosis. 1748 88

Atenolol is a beta(1)-selective drug, which exerts greater blocking activity on beta(1)-adrenoreceptors than on beta(2)-adrenoreceptors, with the S-enantiomer being more active than R-enantiomer. The aim of this study was to investigate the proteins with differential protein expression levels in the proteome of vascular smooth muscle cells (A7r5) incubated separately with individual enantiomers of atenolol using an iTRAQ-coupled two-dimensional LC-MS/MS approach. Our results indicated that some calcium-binding proteins such as calmodulin, protein S100-A11, protein S100-A4, and annexin A6 were down-regulated and showed relatively lower protein levels in cells incubated with the S-enantiomer of atenolol than those incubated with the R-enantiomer, whereas metabolic enzymes such as aspartate aminotransferase, glutathione S-transferase P, NADH-cytochrome b(5) reductase, and alpha-N-acetylgalactosaminidase precursor were up-regulated and displayed higher protein levels in cells incubated with the S-enantiomer relative to those incubated with the R-enantiomer. The involvement of NADH-cytochrome b(5) reductase in the intracellular anabolic activity was validated by NAD+/NADH assay with a higher ratio of NAD+/NADH correlating with a higher proportion of NAD+. The down-regulation of the calcium-binding proteins was possibly involved in the lower intracellular Ca2+ concentration in A7r5 cells incubated with the S-enantiomer of atenolol. Ca2+ signals transduced by calcium-binding proteins acted on cytoskeletal proteins such as nestin and beta-tropomyosin, which can play a complex role in phenotypic modulation and regulation of the cytoskeletal modeling. Our preliminary results thus provide molecular evidence on the metabolic effect and possible link of calcium-binding proteins with treatment of hypertension associated with atenolol.
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PMID:Comparative proteomics analysis of vascular smooth muscle cells incubated with S- and R-enantiomers of atenolol using iTRAQ-coupled two-dimensional LC-MS/MS. 1827 Jan 96

Pyridoxal 5'-phosphate (PLP) and pyridoxamine 5'-phosphate (PMP) are highly versatile coenzymes whose importance is well recognized. The capability of PLP/PMP-dependent enzymes to catalyze a diverse array of chemical reactions is attributed to fine-tuning of the cofactor-substrate interactions in the active site. CDP-6-deoxy-L-threo-D-glycero-4-hexulose 3-dehydrase (E1), along with its reductase (E3), catalyzes the C-3 deoxygenation of CDP-4-keto-6-deoxy-D-glucose to form the dehydrated product, CDP-4-keto-3,6-dideoxy- d-glucose, in the ascarylose biosynthetic pathway. This product is the progenitor to most 3,6-dideoxyhexoses, which are the major antigenic determinants of many Gram-negative pathogens. The dimeric [2Fe-2S] protein, E 1, cloned from Yersinia pseudotuberculosis, is the only known enzyme whose catalysis involves the direct participation of PMP in one-electron redox chemistry. E1 also contains an unusual [2Fe-2S] cluster with a previously unknown binding motif (C-X 57-C-X 1-C-X 7-C). Herein we report the first X-ray crystal structure of E1, which exhibits an aspartate aminotransferase (AAT) fold. A comparison of the E1 active site architecture with homologous structures uncovers residues critical for the dehydration versus transamination activity. Site-directed mutagenesis of four E1 residues, D194H, Y217H, H220K, and F345H, converted E 1 from a PMP-dependent dehydrase to a PLP/glutamate-dependent aminotransferase. The E1 quadruple mutant, having been conferred this altered enzyme activity, can transaminate the natural substrate to CDP-4,6-dideoxy-4-amino-D-galactose without E3. Taken together, these results provide the molecular basis of the functional switch of E1 toward dehydration, epimerization, and transamination. The insights gained from these studies can be used for the development of inhibitors of disease-relevant PLP/PMP-dependent enzymes.
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PMID:Structure and mutagenic conversion of E1 dehydrase: at the crossroads of dehydration, amino transfer, and epimerization. 1849 19

A molecular complex of simvastatin (SV) and glycyrrhyzic acid (GA) (at the ratio of 1 : 4), has been synthesized. The complex named "simvaglyzin" (SVG) was stable in aqeous and aqua-alcohol solutions at GA concentrations exceeding 0.2 mM. In vitro SVG acted as uncompetitive inhibitor of 3-hydroxy-3-methyl-glutaryl-CoA reductase (Ki = 94 nM). Appearance of this inhibitory activity is associated with the cytochrome P450-dependent conversion of SVG. The addition of 1 mM methyrapone into incubation medium fully prevented the inhibition of 3-HMG-CoA reductase. SV and SVG (used at 300 nM concentration) inhibited mevalonate synthesis rate by 39.15+/-8.27% and 38.85+/-3.04%, respectively. In vivo SVG showed dose-dependent cholesterol-lowering effect. In rats the cholesterol-lowering effect of SVG used at daily doses corresponding to 66 and 100 mg/kg of SV was equal to the effect of the daily dose 200 mg/kg of SV. The decreases of total cholesterol level in blood serum were 7%, 9% and 8%, respectively. Myotoxicity of those SVG doses estimated by creatine phosphokinase (CPK) activity in blood serum was lower than that of SV. In rats treated with SV the activity of CPK increased by 79% (p<0.01), while in SVG treated rats by 30% and 36% (p<0.05). Any increase of hepatotoxicity markers alanine aminotransferse or aspartate aminotransferase in blood serum was not observed. The data suggest pharmacological synergism attributed to the SV-GA complex formation and elevated safety of the resultant complex compared with the parent compound.
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PMID:[Cholesterol lowering properties of a complex compound simvastatin with glycyrrhizic acid (simvaglyzin) in experimental models]. 1871 86


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