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

---

Query: EC:3.6.1.3 (ATPase)
65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pituitary tumorigenesis occurs in a transgenic line of mice, alpha-T7, which carries a hybrid transgene composed of the 5' flanking region of the human glycoprotein hormone alpha-subunit gene (1.8 kb) linked to the coding region of the SV40 T-antigen gene (alpha-Tag). Tumor foci were identified within the anterior pituitary of both male and female transgenic mice. In addition to a parenchyma with hypertrophied endocrine cells, mostly of the gonadotrope lineage, we here report the unexpected presence of neural tissue within the anterior pituitary, either as foci as large as 1.0 mm in diameter or greater, or in delicate bundles ramifying amongst the granulated parenchymal cells. Areas richest in neural tissue frequently were associated with tumor tissue composed of giant cells of three varieties, all with electron-lucent cytoplasm and similar organellar distribution including small secretory granules (80-160 nm diameter). In type I cells, the secretory granules were aligned at the plasma membrane; in type II cells, the secretory granules were distributed throughout the cytoplasm; type III cells formed colloid-filled follicles and their secretory granules rarely exceeded 100 nm diameter. These giant cells frequently had bizarre pleomorphic nuclei intensely immunopositive for T-antigen and cytoplasm which was lightly immunopositive for alpha-subunit, and immunopositive either for the LH-beta or TSH-beta subunits. Neural tissue contacted the normal granulated parenchymal cells directly, i.e., without a basal lamina or any connective tissue intervening, but only rarely formed synaptoid junctions with these granulated cells. Synaptoid junctions containing round, smooth vesicles, as well as dense core vesicles, were numerous between the neural processes themselves and between the neural tissue and the giant cells of the tumor tissue. These data suggest that in alpha-T7 transgenic mice the giant cells represent highly transformed gonadotropes or thyrotropes, and that a neurotrophic factor may be expressed by these transformed pituitary parenchymal cells.
...
PMID:Neural tissue within anterior pituitary tumors generated by oncogene expression in transgenic mice. 133 36

Cytochrome-c-oxidase (complex IV) was histochemically studied in oncocytic adenoma (n = 10) and carcinoma of the thyroid gland (n = 3), cystadenolymphomas and oncocytic adenomas of the major salivary glands (n = 9), oncocytic neoplasia of the kidney (n = 1) and in 21 parathyroid glands with primary hyperparathyroidism and adenomatous proliferation (n = 17) and secondary hyperparathyroidism with hyperplasia (n = 4). Only in the parathyroids defects of cytochrome-c-oxidase were found being expressed in all 4 glands with hyperplasia (14 defects) and in 5 of the 17 adenomas (11 defects). All defects were confined to foci with oxyphil cell differentiation, the defect areas varying from 0.09 to 21.10 sq mm in hyperplastic glands and from 0.11 to 13.88 sq mm in adenomas, the size of the oxyphil foci varying from 0.12 sq mm-105.38 sq mm. However, not every oxyphil nodule of a gland was devoid of cytochrome-c-oxidase activity. Of 6 predominantly oxyphil adenomas, 4 showed no defects. No defects were observed either in 2 adenomas without oxyphil cells. Further enzymes of the respiratory chain, succinate dehydrogenase (complex II) and ATP synthetase, (complex V) were devoid of defects. In parathyroids with hyperplasia and oxyphil areas, defects of cytochrome-c-oxidase occurred significantly more often and tended to be larger than in adenomas, statistical analysis revealing a significant correlation between the occurrence of defects and the number of oxyphil foci but not with the total oxyphil area.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Random cytochrome-C-oxidase deficiency of oxyphil cell nodules in the parathyroid gland. A mitochondrial cytopathy related to cell ageing? 133 5

A disulfide, n-butyl 2-imidazolyl disulfide (III-2), recently reported to be more toxic to EMT6 tumor cells under hypoxia has also been shown to be preferentially toxic to KHT/iv cells under hypoxia with an IC90 value 3-fold lower versus that measured in air. The IC90 values for both cell lines were markedly affected when the pHe was decreased. Uptake studies revealed that the disulfide is metabolized at the cell membrane with only one of the metabolites, n-butanethiol, being taken up into the cell. There were no differences in the amount of uptake under oxia or hypoxia. Investigation of potential membrane damage revealed that III-2 was a mixed inhibitor of the enzyme Na+,K(+)-ATPase, from isolated plasma membrane. DNA damage, when examined using plasmid DNA in the absence or presence of glutathione, was absent. Minor single-strand breaks to EMT6 DNA could only be observed following exposure to III-2 at the highest concentrations tested, with no differences observed between treatments in air or under hypoxia.
...
PMID:Effect of a hypoxic tumor cell cytotoxic disulfide on the membrane and DNA of tumor cells in culture. 133 6

Drug-resistant tumor cells actively extrude a variety of chemotherapeutic agents by the action of the multi-drug resistance (MDR1) gene product, the plasma membrane P-glycoprotein. In this report we show that the expression of the human MDR1 gene in cultured Sf9 insect cells via a baculovirus vector generates a high activity vanadate-sensitive membrane ATPase. This ATPase is markedly stimulated by drugs known to interact with the P-glycoprotein, such as vinblastine and verapamil, and the ability of the various drugs to stimulate the ATPase corresponds to their previously observed affinity for this transporter. The drug-stimulated ATPase is not present in uninfected or mock-infected Sf9 cells, and its appearance correlates with the appearance of the MDR1 gene product detected with a monoclonal anti-MDR protein antibody and by labeling with 8-azido-ATP. The drug-induced ATPase requires magnesium ions, does not utilize ADP or AMP as substrates, exhibits a half-maximal activation at about 0.5 mM MgATP, and its maximal activity (about 3-5 mumol/mg MDR protein/min) approaches that of the well characterized ion transport ATPases. These results provide the first direct demonstration of a high capacity drug-stimulated ATPase activity of the human multidrug resistance protein and offer a new and simple assay for the investigation of functional interactions of various drugs with this clinically important enzyme.
...
PMID:Expression of the human multidrug resistance cDNA in insect cells generates a high activity drug-stimulated membrane ATPase. 134 44

Experiments were designed to determine the efficacy of different types of liver cell proliferative stimuli given during exposure to several liver tumor-promoting regimens, on the formation of foci of enzyme-altered hepatocytes. Male Wistar rats were initiated with diethylnitrosamine (150 mg/kg body wt). After a 2 week recovery period animals were subjected to promoting regimens, the resistant hepatocyte model, the phenobarbital model and the orotic acid model. While the rats were on these regimens they were given liver cell proliferative stimulus, either a compensatory type (two-thirds partial hepatectomy or a necrogenic dose of carbon tetrachloride) or a direct hyperplastic stimulus such as that induced by the primary mitogen, lead nitrate. Initiated cells so promoted by these regimens were monitored as foci of enzyme-altered hepatocytes positive for gamma-glutamyltransferase and placental glutathione S-transferase or deficient for adenosine triphosphatase. While carbon tetrachloride and partial hepatectomy-induced compensatory regeneration stimulated the promoting ability of the regimens used, direct hyperplasia could not stimulate the formation of foci and/or nodules from initiated hepatocytes. Evaluation of thymidine incorporation indicated that there was no significant difference in the extent of DNA synthesis in both the proliferative stimuli irrespective of the promoting procedure used.
...
PMID:Mitogen-induced liver hyperplasia does not substitute for compensatory regeneration during promotion of chemical hepatocarcinogenesis. 134 15

Multidrug-resistant human tumor cells overexpress the MDR1 gene product P-glycoprotein, which is believed to function as an ATP-dependent efflux pump. In this study we demonstrate that the partially purified P-glycoprotein, when reconstituted in an artificial membrane, catalyzes drug-stimulated ATP hydrolysis. Plasma membrane proteins of a human multidrug-resistant cell line, KB-V1, were solubilized with 1.4% (wt/vol) octyl beta-D-glucopyranoside in the presence of 0.4% phospholipid and 20% (vol/vol) glycerol, and the crude detergent extract was chromatographed on DEAE-Sepharose CL-6B. The 0.1 M NaCl fraction, enriched in P-glycoprotein but devoid of Na,K-ATPase, was reconstituted by the detergent-dilution method. P-glycoprotein constituted 25-30% of the reconstituted protein in proteoliposomes. ATP hydrolysis by proteoliposomes was stimulated 3.5-fold by the addition of vinblastine but was unaffected by the hydrophobic antitumor agent camptothecin, which is not transported by P-glycoprotein. The stimulatory effect of vinblastine was observed only if the protein was reconstituted in proteoliposomes, suggesting that either the substrate binding site(s) was masked by detergent or that the conformation of the soluble P-glycoprotein might not be suitable for substrate-induced activation. Several other drugs that are known to be transported by P-glycoprotein enhanced the ATPase activity in a dose-dependent manner with relative potencies as follows: doxorubicin = vinblastine greater than daunomycin greater than actinomycin D greater than verapamil greater than colchicine. The basal and vinblastine-stimulated ATPase activities were inhibited by vanadate (50% inhibition observed at 7-10 microM) but were not affected by agents that inhibit other ATPases and phosphatases. These data indicate that the P-glycoprotein, similar to other ion-transporting ATPases, exhibits a high level of ATP hydrolysis (5-12 mumol per min per mg of protein).
...
PMID:Partial purification and reconstitution of the human multidrug-resistance pump: characterization of the drug-stimulatable ATP hydrolysis. 135 64

Patients with medically intractable temporal lobe epilepsy (TLE) undergo medial temporal lobectomy with hippocampectomy for one of two reasons. (1) A lesion (tumor or arteriovenous malformation) adjacent to, but not invasive of, the hippocampus, results in the removal of the lesion and adjacent hippocampus in order to ensure a tumor-free margin. This group will be referred to as tumor-related TLE (TTLE) patients. (2) The operation is performed when depth electrode recordings and other evaluative techniques point to the hippocampus as the focus of seizure initiation. This group will be referred to as cryptogenic TLE (CTLE) patients. Analysis of the hippocampi of these two groups of patients reveals that the TTLE hippocampus is quite similar to that of autopsy subjects in its chemical neuroanatomy. However, the dentate gyrus of the CTLE patients shows considerable morphological and cytochemical reorganization. This reorganization is characterized by a number of features. (1) There is a loss of granule cells which occurs either as a patchy loss and/or a thinning of the granule cell layer. (2) Remaining granule cells which contain dynorphin appear to produce recurrent collaterals into the inner molecular layer of the dentate gyrus. (3) In the subgranular region of the hilus (the polymorphic layer) there is a selective loss of interneurons immunoreactive for somatostatin, neuropeptide Y and substance P. (4) There appears to be an increase in fibers immunoreactive for somatostatin and neuropeptide Y which extend throughout the dentate molecular layer. Somatostatin fibers being less numerous than neuropeptide Y fibers (5). The distributions of a number of neurotransmitter receptors also show striking reorganization in the dentate gyrus of the CTLE hippocampus. (6) Second messenger systems protein kinase C and adenylate cyclase, and Na+, K(+)-ATPase activity, as determined by ouabain binding, is increased in the molecular layer of CTLE. This remodeling of the CTLE hippocampus may hold the key to the mechanisms of hyperexcitability of the granule cells in the hippocampus of this group, and consequently the generation of seizures. The removal of the hippocampus in CTLE patients results in good control of seizures, whereas removal of hippocampi that do not show such reorganization, in a group of patients classified as atypical CTLE patients, results in inadequate seizure control. These findings suggest a complex series of processes in converting the properly regulated granule cells into hyperexcitable ones.
...
PMID:Neurotransmitters and their receptors in human temporal lobe epilepsy. 136 31

Although there is extensive data available on Ca2+ effects in normal tissues, comparatively little is known about its effects or regulation in tumor cells. The present studies were undertaken to investigate whether various extracellular calcium concentrations could modulate the expression of the tumor-associated antigen (TAA) recognized by monoclonal antibody (MAb) 44-3A6. It is highly expressed by the human lung adenocarcinoma cell line A549 and has been shown to be a 40-kD integral plasma membrane protein. Treatment of the A549 cell line with various concentrations of exogenous calcium showed a dose-dependent rise in the internal free calcium levels up to 2.4-2.9 mM (external calcium treatment). At higher concentrations, the internal calcium level showed a decline, indicating a higher calcium efflux. The calmodulin-dependent Ca(2+)-ATPase enzyme involved in calcium homeostasis was assayed under these same conditions. The enzyme activity increased with increasing external calcium concentrations showing a 5-fold increase in cells treated with 4.05 mM calcium. These data suggest that as the internal calcium approaches toxic levels, the Ca(2+)-regulated ATPase activity increases to reduce the calcium overload within the cell. Employing Western blot analysis and immunoperoxidase staining studies, this report shows that the antigen recognized by MAb 44-3A5 on A549 cells increased with an increase in calcium concentration. Evidence that this antigen is phosphorylated is presented using Western blot analysis of a radiolabeled antigen-enriched plasma membrane fraction. The previously reported subcellular localization, and now the phosphorylation and responsiveness to calcium by this TAA, gives it the properties predicted to be seen in a calcium 'pump-like' molecule. Thus, these studies support the hypothesis that this TAA may be important in intracellular calcium concentration control or that it is regulated via some calcium-mediated process.
Tumour Biol 1992
PMID:Changes in the expression of the tumor-associated antigen recognized by monoclonal antibody 44-3A6 in A549 cells due to calcium. 138 56

The observed interaction between p53 and the oncoproteins encoded by several DNA tumor viruses suggests that these viruses mediate their transforming activities at least in part by altering the normal growth regulatory function of p53. In this study we examined the effect of viral oncoprotein expression on the transcriptional transactivation function of wild-type p53 in human cells. Plasmids expressing human p53 were cotransfected with either SV40 large T-antigen or human papillomavirus (HPV) type 16 E6 expression plasmids and assayed for transactivation function using a reporter gene driven by a p53-responsive promoter containing multiple copies of the consensus p53 DNA binding motif, TGCCT. Both large T-antigen and E6 were able to inhibit transactivation by wild-type p53. Furthermore, SV40 T-antigen mutants that are defective for p53 binding were not able to inhibit transactivation and HPV E6 proteins that were either mutant or derived from non-oncogenic HPV types and unable to bind p53, had no effect on p53 transactivation. These results demonstrate the physiological relevance of the interaction of SV40 T-antigen and HPV E6 oncoproteins with p53 in vivo and suggest that the transforming functions of these viral oncoproteins may be linked to their ability to inhibit p53-mediated transcriptional activation.
...
PMID:The transcriptional transactivation function of wild-type p53 is inhibited by SV40 large T-antigen and by HPV-16 E6 oncoprotein. 146 23

A tumor appeared on the back of a transgenic mouse carrying the SV40 T-antigen under control of a mouse major urinary protein promoter. High levels of mRNA for the mitochondrial uncoupling protein (UCP) indicated that the tumor was a hibernoma. The tumor has been established as a transplantable tumor line in nude (nu/nu) mice and used as a source of cells to develop a tissue culture system for analyzing brown fat development and differentiation. Ucp expression in tumor cells cultured in Dulbecco's modified Eagle's medium and 10% fetal calf serum was virtually undetectable. Addition of 10(-7) M norepinephrine resulted in approximately a 30-fold induction of Ucp mRNA within 4 h. The induction by norepinephrine was independent of cell density and also independent of thyroid hormone and insulin during the first 5 days in culture. However, in order to maintain the inducibility of Ucp during prolonged culture periods, it was necessary to supplement the medium with insulin. In contrast to Ucp, the expression of Gdc-1, which encodes the cytoplasmic glycerol-3-phosphate dehydrogenase and which is also induced in brown fat by cold exposure, was repressed by norepinephrine and induced by the addition of insulin. Characterization of the adrenergic receptors required for Ucp induction with agonists and antagonists indicated that beta 1 receptors are predominantly utilized; there is no evidence for utilization of beta 3 and alpha 1 receptors for Ucp induction.
...
PMID:Adrenergic regulation of the mitochondrial uncoupling protein gene in brown fat tumor cells. 160 85


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---