Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.1.25 (triphosphatase)
 1,529 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A number of closely related post-transcriptional facets of RNA metabolism show nuclear compartmentation, including capping, methylation, splicing reactions, and packaging in ribonucleoprotein particles (RNP). These nuclear 'processing' events are followed by the translocation of the finished product across the nuclear envelope. Due to the inherent complexity of these interrelated events, in vitro systems have been designed to examine the processes separately, particularly so with regard to translocation. A few studies have utilized nuclear transplantation/microinjection techniques and specialized systems to show that RNA transport occurs as a regulated phenomenon. While isolated nuclei swell in aqueous media and dramatic loss of nuclear protein is associated with this swelling, loss of RNA is not substantial, and most studies on RNA translocation have employed isolated nuclei. The quantity of RNA transported from isolated nuclei is related to hydrolysis of high-energy phosphate bonds in nucleotide additives. The RNA is released predominantly in RNP: messenger-like RNA is released in RNP which have buoyant density and polypeptide composition similar to cytoplasmic messenger RNP, but which have distinctly different composition from those in heterogeneous nuclear RNP. Mature 18 and 28S ribosomal RNA is released in 40 and 60S RNP which represent mature ribosomal subunits. RNA transport proceeds with characteristics of an energy-requiring process, and proceeds independently of the presence or state of fluidity of nuclear membranes. The energy for transport appears to be utilized by a nucleoside triphosphatase (NTPase) which is distributed mainly within heterochromatin at the peripheral lamina. Photoaffinity labeling has identified the pertinent NTPase as a 46 kD polypeptide which is associated with nuclear envelope and matrix preparations. The NTPase does not appear to be modulated via direct phosphorylation or to reflect kinase-phosphatase activities. A large number of additives (including RNA and insulin) produce parallel effects upon RNA transport and nuclear envelope NTPase, strengthening the correlative relationship between these activities. Of particular interest has been the finding that carcinogens induce specific, long-lasting increases in nuclear envelope (and matrix) NTPase; this derangement may underlie the alterations in RNA transport associated with cancer and carcinogenesis.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Nucleocytoplasmic RNA transport. 241 44

Three rat liver foci bioassays have been compared with respect to their sensitivity by the histochemical demonstration of preneoplastic foci, and by the biochemical determination of alterations in enzyme activities of serum indicating hepatotoxicity. We studied the initiation/promotion schedules according to Oesterle and Deml (A), and according to Pereira (B, Broad Spectrum Protocol), and the initiation/selection protocol according to Tatematsu et al. (C), with diethylnitrosamine (DEN), given as a single initiating dose of 10 and 30 mg/kg body wt respectively. With all schedules Sprague-Dawley rats, either females, 3 weeks old (A), or males, 6 weeks old (B, C) were used. For promotion polychlorinated biphenyls (A) or phenobarbital (B) were administered. Selection was performed with 2-acetylaminofluorene (C). The rats in schemes (B) and (C) underwent partial hepatectomy one day prior to initiation. The number and total area of foci deficient in adenosine-5'-triphosphatase (ATPase) and positive in gamma-glutamyltranspeptidase (GGTase) was evaluated. In the complete schedule with 30 mg of DEN in system (A) foci incidence exceeded that of the other systems by about 7-fold (ATPase) and 2-fold (GGTase) respectively. The lower dose of DEN and all control experiments resulted in a respective lower foci yield. With scheme (C), but not with schemes (A) and (B), e.g. serum fructose-1.6-bisphosphatase and alkaline phosphatase were increased, suggesting liver cell damage. Thus tested with DEN, scheme (A) is most sensitive and causes a low impairment of animals' welfare.
Carcinogenesis 1989 Oct
PMID:Comparison of three rat liver foci bioassays--incidence of preneoplastic foci initiated by diethylnitrosamine. 257 25

The effect of co-administration of diethylnitrosamine (DEN) and Clophen A 50, a commercial mixture of polychlorinated biphenyls (PCB), on pre-neoplastic enzyme-altered islands in livers of female Sprague-Dawley rats was studied. The islands were identified by the loss of adenosine-5'-triphosphatase (ATPase), emergence of gamma-glutamyltranspeptidase (GGTase) and glycogen storage after fasting. DEN was given p.o. (0.4 or 4 mg/kg body wt respectively) twice a week for 11 consecutive weeks. Clophen A 50 (1 or 5 mg/kg body wt respectively) was given alternatively three times a week for 11 weeks. Four groups of rats each received either DEN or PCBs in the respective doses. Control animals were treated with the vehicle or remained untreated. All animals were killed at week 12. In rats treated with 4 mg DEN/kg body wt approximately 80 ATPase-deficient islands/cm2 were observed. Additional treatment with Clophen A 50 enhanced the island number 3-fold. Treatment with 0.4 mg/kg body wt DEN induced 17 islands/cm2. Additional application of Clophen A 50 enhanced the island number approximately 3-fold. The total island area was enhanced to the same extent in both groups. The island incidence in PCB-treated rats and controls was below 1/cm2 with all markers tested. The results indicate that PCBs may exhibit a co-carcinogenic activity.
Carcinogenesis 1986 Oct
PMID:Enhancing effect of co-administration of polychlorinated biphenyls and diethylnitrosamine on enzyme-altered islands induced by diethylnitrosamine in rat liver. 287 10

Preneoplastic liver lesions were produced in female Wistar rats by oral administration of 2-acetylaminofluorene for 165 days succeeded by a carcinogen-free standard diet up to 420 days. During the treatment numerous altered hepatic foci (AHF) and hyperplastic nodules (HN) were detected histochemically by a focal decrease or lack of adenosine-5-triphosphatase and glucose-6-phosphatase (G-6-Pase) activities. In addition, the immunohistochemically demonstrable amount of L-type pyruvate kinase was clearly reduced. The histochemically demonstrated decrease of G-6-Pase was substantiated by microbiochemical determination of the enzyme activity in microdissected material. Moreover, during the experimental period a continuous decrease in glucokinase and an increase in hexokinase was detected microbiochemically within AHF and HN. These alterations indicate a shift in the carbohydrate metabolism from gluconeogenesis to glucose utilization and pentose-phosphate-pathway for biosynthesis of nucleic acids. Beside other oncofetal markers, HK may be used as indicator of the early stages of liver carcinogenesis.
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PMID:Decrease in glucokinase and glucose-6-phosphatase and increase in hexokinase in putative preneoplastic lesions of rat liver. 304 Jul 65

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

The effect of the technical mixture of polychlorinated biphenyls (PCBs) Clophen A 50 on the appearance of enzyme-altered islands initiated by diethylnitrosamine (DEN) in livers of 6 and 3 weeks old female Sprague-Dawley rats was studied. The loss of adenosine-5'-triphosphatase (ATPase), the emergence of gamma-glutamyltranspeptidase (GGTase), and the glycogen storage were used as histochemical markers. Islands were initiated by gastric intubation of 12 X 8 mg DEN/kg body weight/day in adults, or with 1 X 8 mg DEN/kg body weight in weanlings. Clophen A 50 alone initiated only few islands. A dose-dependent enhancement in number and area of islands by an additional treatment with Clophen A 50 of DEN-pretreated animals (2-100 mg/kg body weight/weekly, for 7 weeks) was observed in both age groups. In adults, doses between 2 and 100 mg/kg body weight increased number and area of ATPase-deficient islands 2 to 12-fold. In weanlings, application of 10-100 mg/kg body weight resulted in an increase of number and area up to 7- and 12-fold, respectively. No promoting effect was found with 2 mg/kg body weight compared to DEN-treated weanlings. The number of islands with coincidence of the three histochemical markers was enhanced dose-dependently in adults, and less marked also in weanlings after the application of the promoter.
Carcinogenesis 1984 Mar
PMID:Dose-dependent promoting effect of polychlorinated biphenyls on enzyme-altered islands in livers of adult and weanling rats. 614 72

Female Wistar rats were treated sequentially with 4-dimethylaminoazobenzene (4-DAB) and N-nitrosodiethanolamine ( NDEOL ) for periods of 6 weeks. One group received first 4-DAB (0.06% in the diet) and NDEOL (2000 p.p.m. in the drinking water) thereafter, while the second group was treated in the reversed sequence; control groups received the single agent alone. The extent of foci negative for adenosine-triphosphatase (ATPase) or positive for gamma-glutamyl-transpeptidase (gamma-GT)-activity was quantitated in liver as a means to assess carcinogenic efficacy. A very low response was obtained in rats treated first with 4-DAB and then with NDEOL whereas a strong increase in number and especially in size of foci was observed when 4-DAB was given after NDEOL . The response in this latter group was clearly over-additive. Treatment of rats with either carcinogen alone resulted in similar pattern of increases in the volumetric fraction of liver occupied by ATPase-deficient foci. A differential behaviour, however, was observed with respect to islet size. NDEOL produced large numbers of small foci whereas with 4-DAB only few foci were obtained which grew rapidly in the presence of the carcinogen. These findings are consistent with the hypothesis that 4-DAB, besides acting as an initiator, has very strong promoting activity as was to be expected from the characteristic relationship between carcinogen dose and time of liver tumour induction.
Carcinogenesis 1984 Jun
PMID:Promoting effect of 4-dimethylaminoazobenzene on enzyme altered foci induced in rat liver by N-nitrosodiethanolamine. 614 2

Altered transport of nuclear RNA sequences is an early response to carcinogens. Nuclear envelopes (NE) were isolated and assayed for nucleoside triphosphatase activity (NTPase), on the premise that this enzymatic activity participates in RNA transport. A common feature of the action of five different carcinogens (thioacetamide, 2-acetylaminofluorene, 3'-methyl-4-dimethylaminoazobenzene, dimethylnitrosamine, and aflatoxin B1), at low doses without significant toxicity, was to increase NE NTPase activity and to increase RNA transport, as assessed by the appearance of rapidly labeled RNA in the cytoplasm and by in vitro assay. The increases in NTPase were specific for the NE fraction, and early toxic effects of higher doses initially masked the increases. The induced increases in NE NTPase were long-lived. In contrast, increases in NE NTPase were observed only during the regenerative phase of CCl4 intoxication; the CCl4-induced increase was short-lived and returned promptly to control levels. These changes in NTPase activity were not associated with parallel changes in phosphorylation/dephosphorylation of NE proteins. Increases in NE NTPase and alterations in RNA transport, without attendant nuclear replication, may relate to altered nuclear RNA restriction. This change in a regulatory phenomenon may make these cells more susceptible to further modification, potentially playing a role in the initiation phase of carcinogenesis.
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PMID:Increased nucleoside triphosphatase activity of rat liver nuclear envelope is associated with hepatocarcinogen exposure. 620 70

The promoting effect of Clophen A 50, a commercial mixture of polychlorinated biphenyls (PCBs) on preneoplastic islands, initiated by diethylnitrosamine (DEN), was studied in male and female Sprague-Dawley rats. The islands were identified histochemically by loss of adenosine-5'-triphosphatase (ATPase) and/or emergence of gamma-glutamyltranspeptidase (GGTase). Treatment with 12 X 8 mg DEN/kg body wt./day initiated a similar number and total area of islands in males and females. Additional weekly application of Clophen A 50 (50 or 100 mg/kg body wt./week, for 7 weeks) enhanced the number of ATPase-deficient islands 3-fold in males and 9-fold in females. The total area was increased 4-fold in males and 15-fold in females. Number and area of GGTase-positive islands were similarly enhanced. The emergence of a small number of islands after application of Clophen A 50 alone may indicate a weak carcinogenic potency. PCB treatment caused an increase in liver weight, which amounted to approximately 55% in males and 20% in females compared to controls. This increase is partly due to cell hypertrophy, as indicated by determination of cell size. The mitogenic activity of Clophen A 50 was evaluated by measurement of the mitotic index of unaltered hepatocytes at 24, 48 h, and 7 days after application of a single dose (100/mg/kg body wt.) of Clophen A 50. The mitotic index in control animals of both sexes was approximately 0.3%, and was enhanced approximately 8-fold in males, 24 h after PCB treatment. In females only a slight, non-significant increase was observed. The results indicate that the sex-dependent promoting effect of Clophen A 50 is independent from its mitogenic action.
Carcinogenesis 1982
PMID:Sex-dependent promoting effect of polychlorinated biphenyls on enzyme-altered islands induced by diethylnitrosamine in rat liver. 621 18

In the course of chemically induced liver carcinogenesis as one of the earliest changes, the histochemically demonstrable focal loss of nucleoside 5'-triphosphatase activities (ATPase) is detectable. The exact quantitation and differentiation of these alterations can be achieved by biochemical analysis in microdissected preneoplastic foci. The preparation of focal tissue was facilitated using a microscopic-microdissecting apparatus [1]. By microanalytic determination of hydrolytic cleavage of 32P from gamma 32P-ATP a decrease of total ATPase activity to about 70% was found. Furthermore, the alteration of ATPase activities in course of chemically induced liver carcinogenesis in rats will be described.
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PMID:Biochemical quantification of ATPase activities during liver carcinogenesis. 622 16


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