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

The effect of changing the format of administration as well as the total dose of the promoting agent phenobarbital (PB) on the development of altered hepatic foci (AHF) was determined in an initiation-promotion protocol with female rats fed the purified AIN-76 diet. Effects on the total number of AHF and the volume percentage of liver occupied by AHF were determined for four histochemical markers, the placental form of glutathione S-transferase, gamma-glutamyl-transpeptidase canalicular ATPase, and glucose-6-phosphatase after 16 and 60 weeks of promotion with varying doses and formats of PB, as well as for a further 16-week period in which no PB was administered. At the 16-week point, animals fed 0.1% PB continuously exhibited the largest number and volume percentage of AHF, whereas rats fed 0.1% PB for 4 days followed by 10 days of no PB with continuous repetition of this pattern during the 16-week treatment period exhibited no increase in the number of AHF over control and only a slight increase in volume percentage. Rats fed a continuous repetition of 0.2% PB for 2 days followed by 12 days of no PB exhibited an intermediate increase in the number of AHF as well as the volume percentage fraction after 16 weeks of this regimen. After 60 weeks of feeding PB by these three different formats, the numbers of AHF observed in these groups were equivalent and had increased above those seen after 16 weeks of feeding. The volume percentage occupied by the AHF in these three groups was also similar, although animals receiving 0.2% PB intermittently showed a significantly lower volume percentage than animals receiving 0.1% PB continuously for 60 weeks. When animals were maintained for an additional 16 weeks without PB feeding, the numbers of AHF decreased dramatically, much more so in animals fed PB intermittently, whereas the volume percentage fraction of AHF in livers of animals receiving 0.1% PB continuously for 60 weeks almost doubled. In contrast, the volume percentage fraction of AHF in livers of animals receiving PB intermittently for 60 weeks followed by 16 weeks of no PB was slightly less. Examination of the individual size classes of AHF showed little change in their distribution at 16 and 60 weeks, but after 16 weeks of PB withdrawal (76 weeks total time), the distribution of AHF in animals that had received 0.1% PB continuously for 60 weeks exhibited a decidedly greater shift to larger AHF than animals receiving PB intermittently for the 60-week period.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The effect of the format of administration and the total dose of phenobarbital on altered hepatic foci following initiation in female rats with diethylnitrosamine. 204 80

Critical parameters in the quantitation of altered hepatic foci (AHF) developing during multistage hepatocarcinogenesis in the rat include: 1) the enumeration of AHF induced by test agents as well as those AHF occurring spontaneously in livers of untreated animals; 2) the volume percentage or fraction of the liver occupied by all AHF as a reflection of the total number of altered cells within the liver and the degree of tumor promotion which has occurred; and 3) the phenotype of individual AHF as determined by multiple markers with serial sections. These parameters, especially the number of AHF, should be corrected by the presence of spontaneous AHF which increase with the age of the animal, more so in males than females. While accurate estimation of the background level of spontaneous AHF can be important in demonstrating that a carcinogenic agent does not possess the ability to increase the numbers of AHF above the background level, a better method to distinguish the effectiveness and relative potencies of agents as initiators or promoters is reviewed. The relative effectiveness of four different markers--gamma-glutamyltranspeptidase (GGT), a placental form of glutathione S-transferase (GST), canalicular ATPase, and glucose 6-phosphatase (G6Pase)--was described for the chemicals C.I. Solvent Yellow 14 and chlorendic acid as promoting agents in males and females. C.I. Solvent Yellow 14 is a more effective promoting agent in females than males, and AHF exhibit extremely low numbers scored by GGT. On the other hand, the numbers of AHF present in livers of male rats promoted by this agent are more than twice those seen in livers of female animals, possibly owing to the effectiveness of this agent as an initiator in the male but not the female. Very few AHF, especially in the male, are scored by GGT during chlorendic acid promotion. The distribution of phenotypes with these markers also differs in the spontaneous AHF appearing in the livers of animals fed 0.05% phenobarbital on either a crude NIH-07 or AIN-76 purified diet. Such studies emphasize the extreme dependence of the promoting stage of hepatocarcinogenesis on environmental factors of sex, diet, and the molecular nature of the promoting agent itself. The hallmark of the final stage of progression in the development of hepatocellular carcinomas is aneuploidy, which may be reflected by phenotypic heterogeneity within individual AHF, termed foci-in-foci. The implications of such quantitative analyses during hepatocarcinogenesis induced by specific agents in relation to the specific action of the agent at one or more of the stages of hepatocarcinogenesis are discussed.
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PMID:Critical parameters in the quantitation of the stages of initiation, promotion, and progression in one model of hepatocarcinogenesis in the rat. 269 39

Six groups of F344/N female rats were fed either a modified AIN-76 diet (20% casein, 5% corn oil, 65% cornstarch, 5% cellulose) (AIN) or a diet formulated by Dr. M. Pariza (PD) (30% casein, 10% partially hydrogenated corn oil, 40% sucrose, 15% cornstarch) beginning four days before 70% partial hepatectomy. One day after the surgery, one group fed each diet was intubated with 10 mg/kg diethylnitrosamine (DEN). One week later, these groups plus one control group fed each diet were given 0.05% phenobarbital in the diet for 6 or 14 months. After the rats were killed, blocks of liver tissue were frozen on dry ice and stored at -70 degrees C. Three frozen serial sections were stained for gamma-glutamyltransferase, ATPase, and glucose-6-phosphatase. Numbers and volume of altered hepatic foci (AHF) were analyzed by stereological techniques. After 14 months of feeding these regimens, rats initiated with DEN and fed the AIN + PB had significantly greater numbers and a higher percent volume of the liver of most phenotypes of AHF than all other groups, including those fed PD + PB following initiation with DEN. The numbers of AHF exhibiting more complex phenotypes (i.e., scored by more than one marker) remained unaltered between 6 and 14 months. These findings indicate that the effectiveness of PB as a promoting agent in multistage hepatocarcinogenesis is significantly altered when fed with two different diets of known composition. Therefore, dietary composition can be a significant factor in studies of the stage of promotion in hepatocarcinogenesis.
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PMID:A semipurified diet that suppresses phenobarbital promotion of hepatocarcinogenesis in the rat. 277 2

Sprague-Dawley rats were fed a basal AIN-76 diet containing 80, 200, 350, 500 or 650 mg of magnesium per kilogram of diet for 6 wk. Ventricular slices, as well as microsomal fractions, were prepared from the hearts and were used to determine sodium-potassium pump activity. Sodium-potassium pump activity was assessed in the microsomal membranes by determining the ouabain-inhibitable Na+, K+-ATPase activity and [3H]ouabain binding, and in the ventricular slices, by determining ouabain-sensitive 86Rb uptake under K+-free conditions. The ATPase activity increased with increasing dietary magnesium, so that in the hearts of those animals that were fed 500 and 650 mg of magnesium/kg diet, it was significantly greater than the activity in the hearts of the animals fed 80 and 200 mg/kg diet. Similarly, 86Rb uptake by heart slices from rats fed 500 and 650 mg of magnesium/kg diet was significantly greater than the uptake by heart slices from animals fed 80 and 200 mg/kg diet. [3H]Ouabain binding did not change with increasing dietary magnesium. Thus, magnesium deficiency appears to have no effect on the number of sodium-potassium pump sites, but does decrease the activity of the pump. It is suggested that this leads to an increase in intracellular Na+, resulting in a change in the membrane potential, and may contribute to the arrhythmias associated with magnesium deficiency.
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PMID:Effects of dietary magnesium on sodium-potassium pump action in the heart of rats. 282 28

Female F344/N rats were initiated with DEN (10 mg/kg) 24 h after a 70% partial hepatectomy. Groups of 10 rats were fed (a) AIN, group-1; (b) PD, group-2; or (c) NIH, group-3, for 1 week after initiation and were then fed NIH plus the promoting agent PB at a level of 0.05% in the diets for 6 months. Other groups were fed NIH for 1 week after initiation and then NIH without PB (group-4), AIN + PB (group-5), AIN without PB (group-6), PD + PB (group-7), or PD without PB (group-8) for 6 months. The numbers and volume percentages of AHF were quantified by stereologic methods from frozen serial sections, stained consecutively for GGT, ATPase, and G6Pase. For the groups fed different diets during the 1st week after initiation, the numbers and volume of AHF were significantly greater in group-2 than in groups 1 or 3. The numbers of AHF were significantly less in group-3 than in group-1. The numbers and volume of AHF were significantly greater in groups fed PB during the promotion phase, except in the case of group-7, whose focal volume did not differ from groups 6 or 8. Group-3 had significantly greater numbers of AHF than groups 5 and 7. These findings can be explained by the hypothesis that the NIH diet contained factors that acted synergistically with PB to enhance tumor promotion. The mean focal volume of both GGT positive and ATPase negative foci was significantly greater in group-5 than in all other groups; this indicates that the AIN + PB regimen selectively promoted the growth of a subpopulation of AHF. These findings show that alterations in the composition of diets fed during hepatocarcinogenesis significantly alter the effects of specific chemical agents acting during the stages of initiation and promotion in hepatocarcinogenesis.
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PMID:Dietary effects on initiation and promotion of hepatocarcinogenesis in rat. 289 12

The dose-response characteristics of initiation of hepatocarcinogenesis by diethylnitrosamine (DEN) was investigated in the neonatal female rat by means of the quantitative stereologic estimation of altered hepatic foci (AHF) expressing multiple markers. At 5 days of age, female Sprague-Dawley rats were given a single i.p. dose of DEN (0.1-30 mg/kg body wt) or the vehicle (trioctanoin). The semisynthetic AIN-76A diet was provided to half of the rats in each treatment group, while the remainder received this diet containing 500 mg phenobarbital (PB)/kg for 8 months from weaning until the animals were killed. To ascertain more exactly the dose-response relationship for initiation by DEN, the number, volume percentage and phenotypes of the resulting AHF were determined by quantitative stereological analysis on serial sections of frozen tissue, each stained for one of four markers of preneoplasia. A linear relationship was observed between the dose of DEN (0-30 mg/kg) and the number and volume percentage of AHF detected, with each single marker or the total number of AHF detected when the placental isozyme of glutathione S transferase, gamma-glutamyl transpeptidase (GGT), canalicular adenosine triphosphatase, or glucose-6-phosphatase was used as the marker. For each dose, PB administration increased the number and volume of AHF scored compared with similarly initiated rats that did not receive a promoting stimulus. This was, in part, owing to enhanced GGT expression in AHF with PB administration. Promotion by PB resulted in a distribution of AHF phenotypes altered from that observed in rats not receiving PB. Initiation of AHF in neonatal female rats by DEN was linear with doses from 0 to 30 mg/kg for all four of the phenotypic markers employed. In addition, while PB administration stimulated the growth of all AHF phenotypes, the growth of a subset of AHF that expressed the widest variation in preneoplastic markers was specifically enhanced by PB administration.
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PMID:The effect of the dose of diethylnitrosamine on the initiation of altered hepatic foci in neonatal female rats. 809 61

The purpose of this study was to determine, whether previously reported ethanol-induced alterations to the smooth endoplasmic reticulum (SER), predispose Purkinje neurons (PN) to thapsigargin-induced endoplasmic reticulum (ER) stress. Thapsigargin blocks the sarco/endoplasmic Ca(2+) ATPase pump (SERCA 2), depleting the SER of calcium. Forty-one, eight month old Fischer 344 male rats were treated with either the AIN (American Institute of Nutrition) liquid control or ethanol diets for 10 (n=14), 20 (n=10), or 40(n=17) weeks. At the end of treatment, acute cerebellar slices were prepared by standard means. Cerebellar slices were treated with thapsigargin or as controls for three hours in oxygenated (95% CO2, 5% O2) ACSF (artificial cerebrospinal fluid). Slices were then fixed in 4% paraformaldehyde and sectioned on a freezing microtome. Free floating sections were stained with antibodies against activating transcription factor 6 (ATF6) or activated caspase 12 and calbindin. Results showed a significant increase in the activated caspase+PN dendrites in the EF rats along with a significant interaction due to enhanced expression of activated caspase 12 at 20 weeks. The density of ATF6 labeling was not different between the EF and PF groups and was confined to the PN soma. The finding of activated caspase and ATF6 expression in PN within both the EF and PF groups supports the finding of thapsigargin-induced ER stress. The finding of increased activated caspase 12 in the dendrites supports an increased tendency to ER stress and other dendritic deficits in the ethanol rats.
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PMID:ATF6 and caspase 12 expression in Purkinje neurons in acute slices from adult, ethanol-fed rats. 2497 82