Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.1.3 (ATPase)
 65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The carcinogenic agent benz(a)pyrene inhibits Na, K-ATPase activity of organ homogenates where it is capable of inducing tumors. It causes no significant changes in target organ homogenates.
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PMID:[Effect of benz(a)pyrene and its non-carcinogenic analog 1,2-benzopyrene on the Na, K-ATPase activity of homogenates of different mouse organs and rat heart membrane preparations]. 627 Dec 89

The direct oncogenic potential of radiation and chemicals is demonstrable in cell cultures, where host-mediated influences do not prevail. These systems afford the opportunity of investigating factors that modulate neoplastic transformation. Agents such as retinoids modulate late events and inhibit the expression of transformation and the promotional effects of 12-O-tetradecanoylphorbol-13-acetate. Thyroid hormones play a role in early events, in initiation of transformation. Interaction of triiodothyronine (T3) in a culture medium with single cells is a prerequisite for the initiation of transformation following exposure to X-rays and to benzo[a]pyrene. When cloned hamster embryo cells and mouse 10T 1/2 cells are maintained in a medium containing serum without thyroid hormones (hypothyroid conditions) and exposed to 3 or 4 Gy X-rays, no transformation is observed, although cell survival and cell growth are unaffected by thyroid hormone level. Supplementation of the medium with 10-12M to 10-7M T3 12 h before exposure to X-rays results in a transformation frequency related to the dose of T3, with a peak at 10-10M. The curve is similar to that induced by Na/K ATPase. Addition of T3 at the time of radiation results in a lower transformation frequency; if it is added after radiation no transformation is observed. The effect of T3 in the process of initiation is not mimicked by reverse T3 and is abolished by addition of 100 ng cyclohexamide. The data suggest that the effect of T3 in rendering the cell competent to transform involves synthesis of a cellular 'transforming protein'. Ongoing experiments indicate that exposure to 1 microgram/ml benzo[a]-pyrene results in transformation only in the presence of T3. Under hypothyroid conditions, no transformation is observed.
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PMID:Hormones and the single cell: a relationship prerequisite for transformation. 629 33

The fluorescent maleimide derivatives, 2-(4'-maleimidylanilino)naphthalene 6-sulfonic acid (Mal-ANS) and N-(1-pyrene)-maleimide (Mal-pyrene), both alkylate sulfhydryl groups on the alpha subunit of the (Na,K)-ATPase to inhibit (Na,K)-ATPase and p-nitrophenyl phosphatase activities and phosphoenzyme formation. Reaction of the enzyme with Mal-pyrene, but not with Mal-ANS, also inhibits MgPi- and Mg.ATP.Na-supported [3H]ouabain-binding to the enzyme. Mal-pyrene and Mal-ANS react, in part, with different sulfhydryl groups on the enzyme protein. On the average, the sulfhydryl groups which react with Mal-pyrene are located in a more shielded or hydrophobic environment than are those which react with Mal-ANS. It is the reaction of Mal-pyrene with sulfhydryl groups, which are not accessible to Mal-ANS, that results in the decreased [3H]ouabain-binding capacity of the (Na,K)-ATPase. The results indicate that phosphorylation of (Na,K)-ATPase is not required for Mg.ATP.Na-stimulated ouabain binding, and suggest that the ATP and sodium sites which modulate the interaction of ouabain with the (Na,K)-ATPase may be different from those which promote phosphorylation.
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PMID:Reaction of (Na,K)-ATPase with fluorescent maleimide derivatives. Probes for studying ATP site(s) function. 630 Jan 9

Incubation of primary cultures of hamster embryo cells (HEC) or mouse fibroblasts (C3H/10T1/2 cells) in media depleted of thyroid hormones does not alter cell growth or survival but renders the cells resistant to neoplastic transformation by benzo[a]pyrene (B[a]P) or N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), carcinogens which yield transformation rates of 10(-4)-10(-2) in media supplemented with triiodothyronine (T3). In C3H/10T1/2 cells, the times of addition or removal of the hormone indicate that T3 exerts maximum effect when added 12 hr prior to treatment with B[a]P and that the progression of transformation from the time of initiation by the carcinogen to full expression and the appearance of transformed foci was independent of the presence or absence of the hormone in the medium. Dependence of transformation on T3 concentration in the medium was observed over the physiological range of 1 pM to 100 nM in C3H/10T1/2 cells treated with B[a]P. These results were similar to our previous findings on the T3 dose-related induction of radiogenic transformation and of Na+,K+-ATPase activity. The latter effect was used as a measure of T3 induction of protein synthesis. A further indication of the potential involvement of protein synthesis in T3 action is the suppression of T3- and B[a]P-dependent transformation by cycloheximide at concentrations that inhibit protein synthesis by approximately equal to 50% in the C3H/10T1/2 cells. We suggest that thyroid hormone induces the synthesis of a host protein that plays a key role in neoplastic transformation by direct-acting chemical carcinogens and by those requiring metabolic activation. In our previous studies, similar T3-dependent mechanisms were implicated in radiogenic transformations.
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PMID:Critical role played by thyroid hormone in induction of neoplastic transformation by chemical carcinogens in tissue culture. 631 May 91

It is shown that cholesterol incorporation into the membranes of lymphocytes, lymphoblast leikose cells L1210 and into those of ovary tumor causes an increase in the membrane phospholipid bilayer microviscosity measured by pyrene as a fluorescent probe. An increase in the membrane lipid microviscosity resulted in a decrease in the activity of Na+, K+-ATPase and 51-nucleotidase of the normal and tumor cells. After the injection of the tumor cells with an elevated cholesterol/phospholipid ratio an increase of the life span in the experimental animals as compared with the control group was observed.
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PMID:[Change in the properties of plasma membranes of normal and neoplastic cells after incorporation of cholesterol]. 632 87

The temperature behaviour of the fluorescent probes--1,6- diphenyl-1,3,5-hexatriene (DPH) and pyrene--in the outer and intracellular membranes differs markedly. Fluorescence polarization of DPH in microsomal preparations of duck salt gland and bovine brain enriched with Na,K-ATPase decreases nonmonotonously with an increase in temperature, the critical temperature being coincident with that for Na,K-ATPase. In preparations of sarcoplasmic reticulum intracellular membranes enriched with Ca-ATPase, the DPH fluorescence polarization changes linearly with temperature. Studies of the lipid composition of membrane preparations demonstrated that intracellular membranes are more fluid than outer plasma membranes. At the same time, these membranes reveal a critical temperature for another parameter that characterizes the changes in the hydrophobic volume of the bilayer, i.e., the degree of pyrene excimerization. The Arrhenius plots for this reaction coincide with that for Ca-ATPase in the same preparations.
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PMID:Diphenylhexatriene and pyrene as tools for characterization of biological membranes. 647 33

We have observed quantitative and qualitative differences in the mutability and mutagen-specificity of various drug-resistance marker loci in Chinese hamster ovary (CHO) cells, which suggest that mammalian gene loci may differ in their relative mutability by a given mutagenic agent. We have used the CHO-AT3-2 multiple-marker mutagenesis assay system to examine the dose-dependent induction and kinetics of expression of mutations at four well-characterized, drug-resistance marker loci, after treatment with chemical agents which produce various types of DNA damage. The CHO-AT3-2 subline allows simultaneous quantitation and direct comparison of induced mutation frequencies at the hgprt, oua (Na+/K+ ATPase), aprt, and tk loci. The agents tested in this study included ethyl methanesulfonate, methyl methanesulfonate, mitomycin C, ICR-191, benzo[a]pyrene, and dimethylnitrosamine. The expression kinetics and optimal expression times for each drug-resistance marker were determined in dose-response experiments in which cells from mutagen-treated populations were plated at 1-2-day intervals over a period of 10 days following mutagenesis. Comparison of induced mutation frequencies for each drug-resistance marker after mutagen treatments yielding equivalent cell survivals (equitoxic doses resulting in relative cell survivals of 0.37) revealed locus-specific differences in the relative mutagenicities of the agents tested. These results indicate that the apparent mutagenicity of a particular agent at a single genetic locus may not necessarily be an accurate indicator of that agent's mutagenic potential for the genome as a whole.
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PMID:Induction and expression of mutations at multiple drug-resistance marker loci in Chinese hamster ovary cells. 657 8

Age-dependent alterations of plasmatic membranes were studied in rabbit erythrocytes after separation of erythrocytes of various age by means of centrifugation. The membrane structure characteristics were studied using a fluorescent probe pyrene and spin-labelled probes--nitroxyl derivatives of stearic acid and carboline derivatives. Microviscosity of the membrane lipid phase was shown to increase depending on the cell age. Alterations in the membrane structure were accompanied by a decrease in activity of Na-, K+-ATPase. The content and ratio of membrane lipids were altered with an increase in the cell age, which could be one of reasons of the membrane microviscosity elevation. The age-dependent alterations in erythrocyte membranes may be related, firstly, to the mechanism of old erythrocyte elimination from circulation and, secondly, to be the common characteristic for cell ageing, according to the "membrane hypothesis" of ageing.
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PMID:[Lipid composition and structure-functional properties of membranes of erythrocytes of different ages]. 715 23

Toxicological studies of a leachable stabilizer Di-n-butyltin dilaurate (DBTL) were undertaken. Effects of DBTL after 15 days oral exposure to rats were studied on brain and liver enzyme activities. A significant decrease in body weight gain of DBTL exposed rats were observed. No effect was observed in the activities of brain enzymes, succinic dehydrogenase, adenosine triphosphatase, acetylcholine esterase and monoamine oxidase. In liver, DBTL treatment resulted in a significant decrease in the activities of microsomal enzymes glucose-6-phosphatase, aminopyrine-N-demethylase, benzphetamine-N-demethylase, aniline hydroxylase, benzo(a)pyrene hydroxylase and also on cytochrome P-450 content, whereas no difference in the activities of mitochondrial enzymes, succinic dehydrogenase, Mg2+-adenosine triphosphatase as well as in the activity of lysosomal enzyme acid phosphatase was observed. Duration of exposure dependent increase in pentabarbital induced sleeping time was also observed. DBTL treatment produced an induction in heme oxygenase activity whereas the activity of -aminolevulinic acid synthetase remained unaltered. The results demonstrate that DBTL significantly affects the biotransformation mechanism and heme metabolism of hepatocytes.
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PMID:Toxicological studies of a leachable stabilizer di-n-butyltin dilaurate(DBTL): effects on hepatic drug metabolizing enzyme activities. 726 48

The functional and structural properties of the monomeric and filamentous actin-myosin head (S1) complexes were compared under strictly controlled conditions which avoid the S1-induced polymerization of monomeric actin. Under these conditions, monomeric (G) and filamentous (F) actin were found to activate S1 Mg(2+)-ATPase by 3- and 120-fold, respectively, in the presence of a 5-fold excess of actin over S1. Using the change in fluorescence intensity of pyrene-G-actin induced by S1 binding in the presence of various nucleotide analogues, we discovered that the ternary G-actin-S1-AMPPNP complex could not be formed. Moreover, the association constants of G-actin to S1-ADP or of ADP to the G-actin-S1 complex were at least an order of magnitude lower than in the filamentous state. Such a low affinity between G-actin and the S1-nucleotide intermediates can reasonably explain the lack of ATPase activation by the monomeric complex. Analysis of the G-actin-S1 interface by chemical cross-linking and limited proteolytic experiments showed that, in the monomeric complex, S1 interacted almost exclusively by its positively charged segment 636-642 with the patch of negative residues located on the actin flexible loops 1-7, 20-28, and 90-100. Moreover, the variation in the cross-linking pattern and in the proteolytic susceptibility of S1 segment 636-642 demonstrated that this electrostatic interface was different in the monomeric and the filamentous complexes. Taken together, the results suggested that the G-actin-S1 interaction encompasses only a small fraction of the strong as well as of the weak F-actin-S1 interface. The monomeric complex would in fact resemble more the collision complex which takes place early in the F-actin-S1 interaction.
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PMID:Comparative studies of the monomeric and filamentous actin-myosin head complexes. 754 71


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