Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20020 (adenosine triphosphatase)
 3,299 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Preneoplastic and neoplastic liver cell lesions, induced by EHEN (N-ethyl-N-hydroxyethylnitrosamine) in rats, were investigated to establish the numbers of simultaneously expressed altered enzyme phenotypes within the lesion cells. The lesions were divided into 5 classes on the basis of altered expression in one or more of the following 5 enzymes: glutathione S-transferase placental form, glucose-6-phosphate dehydrogenase, glucose-6-phosphatase, adenosine triphosphatase, and gamma-glutamyl transpeptidase. Class 1 lesions contained cells expressing one altered enzyme. Similarly, class 2, 3, 4 and 5 lesions had cells simultaneously expressing 2, 3, 4, and 5 enzyme alterations, respectively. Four histopathological categories of lesions, ACF (altered cell foci) (274 lesions), HN (hyperplastic nodules) (47 lesions), HCC (hepatocellular carcinomas) (99 lesions) and THC (transplanted hepatocellular carcinomas) (5 lesions) were studied. Proliferation potential was assessed in terms of 5-bromo-2'-deoxyuridine (BrdU) incorporation. The distribution profiles of classes 1 to 5 showed a clear reciprocal change from low class (1 to 2 enzymes) predominance in ACF to high class (4 to 5 enzymes) predominance in HN. Increase of BrdU labeling indices was clearly correlated with progression from HN to HCC. Only a small population of class 5 ACF showed a high BrdU labeling index, indicating particular potential for further development. Thus, the stages of EHEN-induced neoplasia were found to be characterized by gradual increase in the number of altered enzyme phenotypes, with acquisition of proliferative potential being associated with further progression towards malignant conversion.
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PMID:Number of simultaneously expressed enzyme alterations correlates with progression of N-ethyl-N-hydroxyethylnitrosamine-induced hepatocarcinogenesis in rats. 790 86

As demonstrated previously, liver acini draining the blood from intraportally transplanted pancreatic islets in streptozotocin-diabetic rats are altered in various respects. The hepatocytes in these acini store glycogen and/or fat, and they show an increase in proliferation as well as in apoptotic activity. Thus, they are phenotypically similar to carcinogen-induced preneoplastic liver foci (glycogen-storing foci and sometimes also mixed cell foci). By means of catalytic enzyme histochemistry or immunohistochemistry, we investigated the activity of key enzymes of alternative pathways of carbohydrate metabolism and some additional marker enzymes (well known from studies on preneoplastic hepatic foci) in the altered liver acini surrounding the islet isografts. In addition, the expression of glucose transporter proteins 1 and 2 (GLUT-1 and GLUT-2) were investigated immunohistochemically. The activities of hexokinase, pyruvate kinase, glyceraldehyde-3-phosphate dehydrogenase, and glucose-6-phosphate dehydrogenase were increased, whereas the activities of glycogen phosphorylase, adenylate cyclase, glucose-6-phosphatase, and membrane-bound adenosine triphosphatase were decreased in the altered liver acini. The expression of GLUT-2 was also decreased. GLUT-1 and glutathione S-transferase placental form were not expressed, and the activities of glycogen synthase and gamma-glutamyl-transferase remained unchanged. All changes of the enzyme activities were in line with the well known effects of insulin and resembled alterations characteristic of preneoplastic liver foci observed in different models of hepatocarcinogenesis. It remains to be clarified in long-term experiments whether or not these foci represent preneoplastic lesions and may proceed to neoplasia.
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PMID:Altered liver acini induced in diabetic rats by portal vein islet isografts resemble preneoplastic hepatic foci in their enzymic pattern. 864 65

The role of oxidative stress in chronic cadmium (Cd) toxicity and its prevention by cotreatment with beta-carotene was investigated. Adult male rats were intragastrically administered 2 mg CdCl2/kg body weight three times a week intragastrically for 3 and 6 weeks. Brain and testicular thiobarbituric acid reactive substances (TBARS) was elevated after 3 and 6 weeks of Cd administration, indicating increased lipid peroxidation (LPO) and oxidative stress. Cellular damage was indicated by inhibition of adenosine triphosphatase (ATPase) activity and increased lactate dehydrogenase (LDH) activity in brain and testicular tissues. Chronic Cd administration resulted in a decline in glutathione (GSH) content and a decrease of superoxide dismutase (SOD) and glutathione S-transferase (GST) activity in both organs. Administration of beta-carotene (250 IU/kg i.g.) concurrent with Cd ameliorated Cd-induced LPO. The brain and testicular antioxidants, SOD, GST, and GSH, decreased by Cd alone, were restored by beta-carotene cotreatment. Concurrent treatment with beta-carotene also ameliorated the decrease in ATPase activity and the increase in LDH activity in brain and testis of Cd-treated rats, indicating a prophylactic action of beta-carotene on Cd toxicity. Therefore, the results indicate that the nutritional antioxidant beta-carotene ameliorated oxidative stress and the loss of cellular antioxidants and suggest that beta-carotene may control Cd-induced brain and testicular toxicity.
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PMID:Role of beta-carotene in ameliorating the cadmium-induced oxidative stress in rat brain and testis. 1096 95

Curcumin, a yellow pigment of turmeric (Curcuma longa), is a commonly used spice and a coloring agent in foods, drugs, and cosmetics. Curcumin is known to possess chemopreventive properties in various animal tumor models. In the present study the effect of curcumin on the development of altered hepatic foci (AHF), by using a medium term liver bioassay, has been evaluated. AHF were analyzed by quantitative stereology using the Leica Qwin Image Analysis system from frozen liver sections stained for g-glutamyl transferase, adenosine triphosphatase, glucose-6-phosphatase, alkaline phosphatase, and placental isozyme of glutathione S-transferase. A significant protection on diethylnitrosamine (DEN) initiated and 2-acetylaminofluorene (AAF) promoted AHF by curcumin was observed on these biological markers. The curcumin administration was found to restore the normal levels of the enzymes glutathione S-transferase and g-glutamyl transferase in rat liver following DEN-AAF exposure. Similarly, a significant protection was provided by curcumin in the enzyme-deficient foci for the adenosine triphosphatase-, alkaline phosphatase-, and glucose-6-phosphatase-treated groups in comparison to the DEN-AAF-treated group. These results show that curcumin can effectively suppress the DEN-induced development of AHF in rat liver.
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PMID:Suppression of altered hepatic foci development by curcumin in wistar rats. 1279 5

The high-affinity ligand-binding form of unactivated steroid receptors exists as a multicomponent complex that includes heat shock protein (Hsp)90; one of the immunophilins cyclophilin 40 (CyP40), FKBP51, or FKBP52; and an additional p23 protein component. Assembly of this heterocomplex is mediated by Hsp70 in association with accessory chaperones Hsp40, Hip, and Hop. A conserved structural element incorporating a tetratricopeptide repeat (TPR) domain mediates the interaction of the immunophilins with Hsp90 by accommodating the C-terminal EEVD peptide of the chaperone through a network of electrostatic and hydrophobic interactions. TPR cochaperones recognize the EEVD structural motif common to both Hsp90 and Hsp70 through a highly conserved clamp domain. In the present study, we investigated in vitro the molecular interactions between CyP40 and FKBP52 and other stress-related components involved in steroid receptor assembly, namely Hsp70 and Hop. Using a binding protein-retention assay with CyP40 fused to glutathione S-transferase immobilized on glutathione-agarose, we have identified the constitutively expressed form of Hsp70, heat shock cognate (Hsc)70, as an additional target for CyP40. Deletion mapping studies showed the binding determinants to be similar to those for CyP40-Hsp90 interaction. Furthermore, a mutational analysis of CyP40 clamp domain residues confirmed the importance of this motif in CyP40-Hsc70 interaction. Additional residues thought to mediate binding specificity through hydrophobic interactions were also important for Hsc70 recognition. CyP40 was shown to have a preference for Hsp90 over Hsc70. Surprisingly, FKBP52 was unable to compete with CyP40 for Hsc70 binding, suggesting that FKBP52 discriminates between the TPR cochaperone-binding sites in Hsp90 and Hsp70. Hop, which contains multiple units of the TPR motif, was shown to be a direct competitor with CyP40 for Hsc70 binding. Similar to Hop, CyP40 was shown not to influence the adenosine triphosphatase activity of Hsc70. Our results suggest that CyP40 may have a modulating role in Hsc70 as well as Hsp90 cellular function.
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PMID:Interaction of the Hsp90 cochaperone cyclophilin 40 with Hsc70. 1549 3

Diallyl sulphide (DAS) is a sulphur-containing volatile compound present in garlic (Allium sativum). It has been shown to inhibit a number of chemically induced forms of cancer in experimental animals. The present study demonstrates the inhibitory effect of DAS on the development of diethylnitrosamine (DEN) initiated and 2-acetyl-aminofluorene (2-AAF) promoted preneoplastic altered hepatic foci (AHF) in Wistar rats. AHF were scored and analysed by quantitative stereology using the Image Analysis system from frozen liver sections stained for biological markers, namely glutathione S-transferase, placental form (GST-P), gamma-glutamyl transpeptidase (GGT), adenosine triphosphatase (ATPase), glucose-6-phosphatase (G6 Pase) and alkaline phosphatase (AlkPase). DAS-supplemented rats were found to restore the near-normal levels of enzymes GST-P and GGT when exposed to DEN and 2-AAF. DAS administration following DEN and 2-AAF exposure led to the restoration of enzymic activity of ATPase, G6 Pase and AlkPase, as evident by number and area of the foci. These findings suggest the protective role of DAS in rat hepatocarcinogenesis, by suppressing DEN- and 2-AAF-induced AHF development.
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PMID:Modulation of altered hepatic foci induction by diallyl sulphide in Wistar rats. 1555 53

Indole-3-carbinol (I3C) is a cleavage product of glucobrassicanin, a natural compound present in a wide variety of plant food substances including members of the family Cruciferae. I3C is known to possess cancer-chemopreventive potential in various animal models. The present study reveals the protective effect of I3C on the development of diethylnitrosamine (DEN)-initiated and 2-acetylaminofluorene (AAF)-promoted preneoplastic, altered hepatic foci (AHF) in Wistar rats. I3C was given at dose levels of 0.5 and 1 mg/kg body weight for five consecutive days along with DEN and AAF. AHF were scored and analyzed by quantitative stereology using the Image Analysis System from frozen liver sections stained for positive and negative biological markers of AHF, that is, glutathione S-transferase (GST-P), gamma-glutamyl transpeptidase (GGT), glucose-6-phosphatase (G6Pase), adenosine triphosphatase (ATPase), and alkaline phosphatase (AlkPase). Results revealed the chemopreventive effect of I3C on the DEN-initiated AHF in Wistar rats. The expression of G6Pase, ATPase, and AlkPase was restored in the I3C-supplemented animal. Similarly the induced expression GST-P and GGT also decreased in the animals with I3C administration. The recovery of altered levels of these biomarkers was of comparatively higher magnitude in the animals given a higher dose of I3C (1 mg/kg body weight) in comparison with the animals given 0.5 mg/kg body weight dose of I3C, although no dose-dependence pattern was recorded in I3C-supplemented groups. These results thus suggest the chemopreventive effect of I3C in rat hepatocarcinogenesis by suppressing DEN- and AAF-induced AHF development.
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PMID:Chemopreventive effect of indole-3-carbinol on induction of preneoplastic altered hepatic foci. 1562 69

The present study was designed to evaluate the protective role of zinc in attenuating the adverse effects induced by lithium in blood of female Wistar rats. Female Wistar rats received lithium in the form of lithium carbonate in diet at a dose level of 1.1 g/kg diet, zinc alone in the form of zinc sulfate in drinking water at a dose level of 227 mg/L drinking water, or lithium plus zinc treatments in the combined group for a total duration of 2 months. Effects of the treatments were studied on antioxidant defense system, various hematologic parameters, and percentage of (65)Zn-specific activity. Lithium treatment resulted in a significant increase in lipid peroxidation levels but caused a significant decrease in reduced glutathione levels and the activities of catalase, glutathione S-transferase, and superoxide dismutase. Lithium treatment also caused a significant decrease in the activities of aminolevulinic acid dehydratase and Na(+) K(+) adenosine triphosphatase. However, it resulted in a significant increase in total leukocyte counts, neutrophils, and lymphocyte counts as well as zinc protoporphyrin levels, whereas a significant decrease in counts of monocytes, eosinophils, and percentage specific activity of (65)Zn in blood and its various fractions was noticed. Furthermore, lithium treatment caused a significant decrease in serum zinc levels. However, zinc supplementation to lithium-treated rats effectively raised the reduced glutathione levels and also normalized lipid peroxidation and the activities of antioxidative enzymes, which included catalase, glutathione S-transferase, and superoxide dismutase. Moreover, zinc supplementation could raise the activities of the enzymes aminolevulinic acid dehydratase and Na(+) K(+) adenosine triphosphatase as well as the percentage uptake values of (65)Zn in blood and its fractions. The study suggests that zinc, as a nutritional supplement, has the potential in attenuating most of the adverse effects induced by lithium in rat blood.
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PMID:Zinc improves antioxidative enzymes in red blood cells and hematology in lithium-treated rats. 1908 87

Using rare minnow (Gobiocypris rarus) at early-life stages as experimental models, the developmental toxicity of five widely used triazole fungicides (myclobutanil, fluconazole, flusilazole, triflumizole, and epoxiconazole) were investigated following exposure to 1-15 mg/L for 72 h. Meanwhile, morphological parameters (body length, body weight, and heart rate), enzyme activities (superoxide dismutase (SOD), glutathione S-transferase (GST), adenosine triphosphatase (ATPase), and acetyl cholinesterase (AChE)), and mRNA levels (hsp70, mstn, mt, apaf1, vezf1, and cyp1a) were also recorded following exposure to 0.2, 1.0, and 5.0 mg/L for 72 h. Results indicated that increased malformation and mortality, decreased body length, body weight, and heart rate provide a concentration-dependent pattern; values of 72 h LC50 (median lethal concentration) and EC50 (median effective concentration) ranged from 3 to 12 mg/L. Most importantly, the results of the present study suggest that even at the lowest concentration, 0.2 mg/L, five triazole fungicides also caused notable changes in enzyme activities and mRNA levels. Overall, the present study points out that those five triazole fungicides are highly toxic to the early development of G. rarus embryos. The information presented in this study will be helpful in better understanding the toxicity induced by triazole fungicides in fish embryos.
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PMID:Triazole-induced toxicity in developing rare minnow (Gobiocypris rarus) embryos. 2502 28

Penconazole is one of the most widely used fungicides all over the world, and since it spreads to large environments, its toxic effects on non-target organisms are of great concern. The toxic effects of penconazole on crayfish (Astacus leptodactylus), which is a bioindicator in freshwater ecosystems and consumed economically, are not known. Therefore, in this study, the purpose was to contribute to the literature on the potential harmful effects of penconazole on a non-target species, Astacus leptodactylus. For this aim, the acute toxicity (96 h) of penconazole was examined. The 96-h LC50 value of penconazole was detected as 18.7 mg L-1. Four concentrations of penconazole (18.7 mg L-1, 9.35 mg L-1, 4.68 mg L-1, 2.34 mg L-1) were applied to crayfish for 96 h. The results showed that penconazole had destructive effects on esterase mechanisms by inhibiting acetylcholinesterase (AChE) and carboxylesterase (CaE) activities. Significant increases were observed in all antioxidant parameters (superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST), reduced glutathione (GSH), malondialdehyde (MDA)) in all doses except the lowest concentration (2.34 mg L-1). All adenosine triphosphatase (ATPase) activities (Na+/K+-ATPase, Mg2+-ATPase, Ca2+-ATPase, total ATPase) had significant dose-related inhibition in both gill and muscle tissues. In summary, our findings show that acute penconazole administration to crayfish causes significant toxic effects on esterase, antioxidative parameters, and metabolic enzymes.
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PMID:Acute exposure to the fungicide penconazole affects some biochemical parameters in the crayfish (Astacus leptodactylus Eschscholtz, 1823). 3260 70


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