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)

We have recognized an experimental confluence between oxidative phosphorylation and chemical carcinogenesis and, therefore, became interested in the mitochondrial target of hydrazine, which is not only a potential environmental hazard as a carcinogen but is also a likely metabolite of many drugs. Hydrazine induced a Pi dependent transitory uncoupling of rat liver mitochondria when beta-hydroxybutyrate was the substrate. Uncoupling was inhibited by rutamycin; accordingly, the mitochondrial target for nucleophilic hydrazine is an electrophilic site, presumably involving activated Pi. The protective action of ATP2, ADP, PPi and Mg++ was attributed to a conformational change of the phosphorylating enzyme which participated in oxidative phosphorylation. In a mitochondrial system which included ATP gramicidin potassium ion and sulfate, hydrazine, acting as a large cation but not as a nucleophile, blocked mitochondrial swelling and the increment in ATPase activity associated with potassium ion. These data in conjunction with our previous reports dealing with other carcinogens and certain of their derivatives also contribute to an experimental confluence between oxidative phosphorylation and chemical carcinogenesis and are compatible with toxic effects of hydrazine on mitochondria observed previously by others.
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PMID:A requirement of Pi for the transitory uncoupling of rat liver mitochondria by hydrazine, when beta-hydroxybutyrate is the substrate. 8 99

After topical treatment of cheek pouches of 10 hamsters with 9,10-dimethyl-1,2-benzanthracene and 2,4-dinitrophenol for 10 weeks no carcinomas developed in any of the animals. After treatment of 10 animals with the carcinogen only, there were 49 carcinomas in the 8 survivors. Inhibition of chemical carcinogenesis by dinitrophenol was tentatively attributed to suppression of ATP synthesis and to activation of ATPase by dinitrophenol.
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PMID:Inhibition by 2,4-dinitrophenol of 9,10-dimethyl-1,2-benzanthracene carcinogenesis in the hamster cheek pouch. 12 26

In a search to determine common molecular features in potential carcinogenic dietary fatty acids, Swern et al. (1970) found that 12-hydroxystearic acid and its methyl ester were carcinogenic. This was surprising to Swern et al. (1970) and Van Duuren et al. (1972), as it was not readily apparent how such agents could be converted to alkylating agents. We have observed that the carcinogens 12-hydroxystearic acid and its methyl ester disrupted oxidative phosphorylation in rat liver mitochondria. The in vitro mitochondrial effects induced by the agents included: a) uncoupled respiration, b) ATPase activity, c) energized volume changes linked either to respiration or ATP. Mitochondria mediated the enzymic conversion of the ester to the acid. Conversion was retarded by the thiol reagent showdomycin. These data in conjuction with our previous reports dealing with other carcinogens and their derivatives contribute to an experimental confluence between oxidative phosphorylation and chemical carcinogenesis.
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PMID:The disturbance of oxidative phosphorylation in rat liver mitochondria by the carcinogens 12-hydroxystearic acid and its methyl ester. 15 99

Uvomorulin (E-cadherin), a cell adhesion molecule, and Na+,K(+)-adenosine triphosphatase (ATPase), a marker protein of the basal-lateral cell membrane domains of polarized epithelial cells, were investigated in a group of mouse skin tumors induced by a two-stage chemical carcinogenesis protocol and in cell lines derived from mouse skin papillomas and squamous cell carcinomas (SCC). Although these two markers were present in benign tumors and in nontumorigenic cell lines, the Na+,K(+)-ATPase showed an altered pattern of distribution that included the presence of enzyme not only in the basolateral domain but also on the apical domain of the cell membrane of basal and spinous cells in well-differentiated squamous cell carcinomas (SCC). In higher grade SCC, a loss of Na+,K(+)-ATPase immunoreactivity was simultaneously detected with a marginal or absent expression of uvomorulin. The more differentiated SCC and papillomas expressed less uvomorulin immunoreactivity than normal epidermal cells. Both markers were seen in tumor cell lines that produced well-differentiated SCC after subcutaneous inoculation into nude mice. Neither Na+,K(+)-ATPase nor uvomorulin could be detected in cell lines that produced high grade, poorly differentiated SCC. Northern blots confirmed the absence of uvomorulin mRNA in these highly malignant cell lines. These data indicate that progression from premalignant papilloma to low-grade SCC and subsequently to high-grade SCC is accompanied by loss of epithelial cell polarity as detected by changes in Na+,K(+)-ATPase and by decreased or absent expression of uvomorulin in tumors and cell lines characterized by an advanced malignant phenotype.
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PMID:Alterations in the expression of uvomorulin and Na+,K(+)-adenosine triphosphatase during mouse skin tumor progression. 131 85

During chemical carcinogenesis Langerhans cells (LC) are depleted from the epidermis, disrupting the normal immunological functions of the skin. Tumor promotors but not initiators, have been shown to deplete adenosine triphosphatase (ATPase)-positive LC from the skin and therefore the cutaneous immune system may be impaired during tumor promotion but not initiation. The present study shows that the tumor promotor 12-O-tetradecanoylphorbol 13-acetate (TPA) but not the initiator urethane depletes Ia-positive LC from BALB/c murine ear epidermis, and beta-glucuronidase-positive LC from C57BL mouse tail skin. Sensitization with 2,4-dinitrofluorobenzene (DNFB) through urethane-treated skin resulted in a normal contact sensitivity response when the mice were challenged 5 days later. In contrast, tolerance resulted from sensitization through TPA-treated skin as a result of the generation of suppressor cells. In addition, TPA but not urethane-treated C57BL mouse tail skin survived for an extended time when grafted onto histoincompatible BALB/c mice. Therefore, impairment of the normal immunological functions of skin resulted from treatment with the tumor promotor TPA but not the tumor initiator urethane, which suggests that a loss of LC during tumor promotion may impair immunological protection against skin tumors.
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PMID:Suppressor cell activation and enhanced skin allograft survival after tumor promotor but not initiator induced depletion of cutaneous Langerhans cells. 296 90

Previous research by the authors had suggested that uridine-diphosphate-glucuronyl-transferase (UDP-GT) is a useful preneoplastic marker in chemical carcinogenesis. Recently the authors report that they found typical clear cell foci in a macroscopically normal liver surrounding focal nodular hyperplasia with a 6 cm diameter in a 27-year old woman who had been using oral contraceptives (OCs) containing ethinyl-estradiol and lynestrenol for 9 years. These foci were further characterized by a reduction of canalicular and cytoplasmic ATPase activity, an increased glycogen content, and a positive immunohistochemical reaction for UDP-GT. OC users develop 2 basic types of benign liver tumors: hepatic adenoma and focal nodular hyperplasia. Hepatic adenoma appears to be caused by OCs, whereas the relationship between OC use and focal nodular hyperplasia is less clear. The tumorigenic action of OCs has been ascribed to a promotor action on liver cells; however, there is no evidence that OCs are initiators of liver tumors. The case reported shows 2 manifestations of toxic lesions promoted by OC use: the development of focal nodular hyperplasia and enzyme-altered foci comparable to those seen in experimental liver carcinogenesis. Further studies are needed to get more information about the preneoplastic potential of these foci in humans. Since enzyme-altered foci could not be identified in the liver tissue of healthy women, these foci may be of prognostic significance in longterm OC users.
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PMID:Increased UDP-glucuronyltransferase in putative preneoplastic foci of human liver after long-term use of oral contraceptives. 392 52

Enzyme biochemical and histochemical assays during chemical carcinogenesis in rat liver have revealed that several adult enzyme activities are lost and some fetal enzyme activities are re-expressed in the hyperplastic foci as well as in the developed hepatomas. How these enzyme alterations are acquired and to what extent these changes are specifically related to the growth alterations leading to neoplastic development are decisive questions. Using a carcinogenesis protocol that combines a single dose of diethylnitrosamine and phenobarbital given continuously as the promoting agent and by assaying serial liver sections for glucose-6-phosphatase, adenosine-5'-triphosphatase and 5'-nucleotidase, we have identified the three-enzyme pattern of 1,746 islands and measured their section areas. We found a clear trend that clones with more deviated enzyme pattern grow faster than less deviated ones.
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PMID:Enzyme pattern and growth rate of liver preneoplastic clones during carcinogenesis by diethylnitrosamine. 608 33

Radiation-induced carcinogenesis of the rat liver using iridium-192 seeds as an intrahepatic radioactive source was studied by enzyme histochemical means. Rats were divided into six groups according to various combinations of one or two iridium-192 or stainless steel seeds and whether they were given a diet containing 0.05% phenobarbital (PB) or a basal diet (BD). Each group were sacrificed at 20, 40, and 60 weeks after intrahepatic insertion of the iridium-192 or stainless steel seeds. gamma-Glutamyl transpeptidase (GGT), glucose-6-phosphatase (G6Pase), and adenosine triphosphatase (ATPase) were stained in the liver tissues, and GGT-positive foci were quantified. Liver neoplasm was not evident, but enzyme-altered foci (EAF) were induced by gamma-ray irradiation. At every point (20, 40, and 60 weeks) after the insertion of the seeds, the GGT-positive area was larger in the rats given than those given BD. Moreover, despite the iridium-192 radioactivity decay, EAF developed continuously in the rats given PB, and persisted in those given BD from 40 to 60 weeks after insertion. These results indicated that phenobarbital promotes the development of EAF initiated by irradiation, as it promotes the process of chemical carcinogenesis in the rat liver.
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PMID:Promoting effects of phenobarbital on the enzyme-altered foci induced by intrahepatic gamma-ray-irradiation in the rat liver. 884 57

A novel spermatogenesis associated factor (SPAF) was found to be aberrantly expressed at the malignant conversion stage in a clonal epidermal model of chemical carcinogenesis. Sequence analysis revealed two ATPase modules, classifying this gene as a new member of the AAA-protein family (ATPase associated with diverse activities). Immunohistochemical staining of mouse testis sections with SPAF antibody localized expression to spermatogonia and early spermatocytes in the basal compartment of the seminiferous tubules. Northern and Western analysis of SPAF expression in testes of mice at different developmental stages confirmed its expression at early stages of spermatogenesis. In view of a mitochondrial-localization-like signal, sequence similarities to membrane-associated proteins, ATP binding properties, and intracellular expression patterns in testis, we speculate that SPAF protein may be involved in morphological and functional mitochondrial transformations during spermatogenesis. Ectopic expression of the SPAF gene in malignant epidermal cells may signify adoption of an early germ cell-like phenotype advantageous in malignant conversion.
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PMID:SPAF, a new AAA-protein specific to early spermatogenesis and malignant conversion. 1073 18