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)

NAD+ reduction catalyzed by transhydrogenase (EC 1.6.1.1) from E. coli membrane particles at the expense of NADPH oxidation is coupled with phenyldicarbaundecaborate (PCB-) absorption by the particles. This process is inhibited by oxidative phosphorylation protonophorous uncouplers and by equilibration of concentrations of the substrates and products of the transhydrogenase reaction. Elimination of the water-soluble part of membrane ATPase results in the inhibition of PCB- absorption at the expense of the transhydrogenase reaction energy. Treatment of the particles by dicyclohexyl carbodiimide increases the transhydrogenase-coupled absorption of PCB-. The transhydrogenase-induced increase of pPCB in the suspension of particles is directly correlated with the ratio of ([NADPH].[NAD+])/([NADP+].[NADH]). When this value is equal to 1, no energy-dependent increase of pPCB was observed. NADP+ reduction at the expense of NADH oxidation leads to a decrease in the amount of PCB- absorbed by the particles at the expense of ATP hydrolysis energy. The experimental data suggest that NADPH oxidation in the course of the transhydrogenase reaction is coupled with the formation of a membrane potential with a positive charge localized inside the particles.
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PMID:[Transhydrogenase as an additional site of energy accumulation in the E. coli respiratory chain]. 3 31

In the present study the promoting activity of various PCB and PBB isomers and congeners in rat liver has been studied and compared with a variety of primary xenobiotic-mediated enzymatic changes in this target organ. Female Wistar rats were given diethylnitrosamine (DEN; 10 mg/kg body wt for 10 days) and were subsequently treated once weekly with polychlorinated biphenyls (150 or 15 mumol/kg body wt) for a total of 8 weeks. Additional groups of rats were administered 3,3',4,4'-tetrabromobiphenyl or 3-methylcholanthrene (8 weekly injections of 15 or 150 mumol/kg body wt, respectively) or were given phenobarbital (0.05% in the diet) until the end of the experiment. Reference groups were treated with the various test compounds without prior initiation. One week and 9 weeks after cessation of promoter treatment rats were killed and the volumetric fraction of enzyme-altered foci characterized by changes in adenosine triphosphatase and gamma-glutamyl transpeptidase activity was determined as a means to quantitatively assess the extent of preneoplastic response in this organ. Out of the series of polyhalogenated biphenyls tested, promoting effects were seen with the following compounds: 2,2',4,5'-tetrachlorobiphenyl, 3,3',4,4'-tetrachlorobiphenyl, 2,3,4,4',5-pentachlorobiphenyl, and 3,3',4,4'-tetrabromobiphenyl, whereas no significant effects were obtained with 4-monochlorobiphenyl. In rats not treated with DEN, the two strongly promoting agents 2,3,4,4',5-pentachlorobiphenyl and 3,3',4,4'-tetrachlorobiphenyl also significantly increased the volume fraction of enzyme-altered foci over the respective controls when analyzed at the second time point of investigation. In parallel experiments, induction of liver growth and of microsomal cytochrome P450 content in liver was found to correlate well with the promoting activity of the various xenobiotics, suggesting that these parameters may be used to predict the promoting activity of polyhalogenated biphenyls in a short term assay.
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PMID:Effects of polychlorinated biphenyls in rat liver: correlation between primary subcellular effects and promoting activity. 168 70

The pesticide p-p'-DDT and its persistent metabolite p-p'-DDE cause thinning of the eggshells in several species of birds. In earlier investigations on ducks this thinning was found to be associated with a reduction of the ATP-dependent Ca2+ binding to a homogenate of the shell gland mucosal cells by DDE. The activity of a Ca2+-Mg2+-activated ATPase in the homogenate was also decreased on administration of DDE in vivo. We have therefore investigated the in vitro effects of some other chlorinated hydrocarbon pesticides of ecotoxicological interest on the ATP-dependent Ca2+ binding and the Ca2+-Mg2+-activated ATPase activity in a homogenate of the eggshell gland mucosa of the hen and determined the molar concentrations that produced 50% inhibition (=IC50). Several of the investigated compounds, namely toxaphene, chlordane, p-p'-DDD, o-p'-DDE, p-p'-DDT, methoxychlor and PCB (Arochlor 1242), had a similar IC50 to inhibit the Ca2+ binding as p-p'-DDE. Lindane, p-p'-DDA and biphenyl had an IC50 3.3-4 times higher and that of 2.4 D was 13.5 times higher than that of p-p'-DDE. When the IC50 of some of the compounds (p-p'-DDE, PCB, toxaphene, Lindane) was determined that decreased the Ca2+-Mg2+-activated ATPase of the homogenate it was found to be only 18 to 29 per cent of that needed to inhibit the Ca2+ binding by the homogenate. It is therefore probable that some other effect than inhibition of this enzyme is also involved in the Ca2+-binding process and affected by the compounds.
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PMID:The inhibitory effect of some chlorinated hydrocarbon pesticides on the ATP-dependent Ca2+ binding of the particulate fraction of the eggshell gland mucosa cells. 613 49

Polychlorinated biphenyl (PCBs) mixtures contain a number of different congeners, some of which have been proposed to be neuroactive. Recent studies have suggested that ortho-substituted PCBs may be neuroactive, while 'dioxin-like' non-ortho-substituted congeners are not. This study compared the in vitro effects of a putative neuroactive ortho-biphenyl (2,2'-dichlorobiphenyl; DCBP) with that of a putative non-neuroactive congener lacking ortho-chlorine substitutions (3,3',4,4',5-pentachlorobiphenyl; PCBP) on Mg(2+)-ATPase activity in mitochondrial and synaptosomal preparations from striatum, hypothalamus, cerebellum and hippocampus. In these studies, DCBP significantly inhibited oligomycin-sensitive (OS) Mg(2+)-ATPase activity in all four brain regions in a concentration-dependent manner; PCBP, on the other hand, had no effect on OS Mg(2+)-ATPase activity in any brain region examined at concentrations up to 100 microM. The striatum, a dopamine-rich region, was not preferentially sensitive to the effects of DCBP. Furthermore, DCBP did not inhibit synaptosomal Na+/K(+)-ATPase activity, suggesting a specificity of action on OS Mg(2+)-ATPase. These data support previous structure-activity relationships, suggesting that ortho-substituted PCB congeners are neuroactive while non-ortho-substituted congeners are not. Disruption of mitochondrial oxidative energy production may play a role in the neuroactivity of ortho-chlorinated PCBs.
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PMID:Sensitivity of adenosine triphosphatases in different brain regions to polychlorinated biphenyl congeners. 808 84

Activation of the hypothalamus-pituitary-interrenal (HPI) axis is characteristic of stress responses, which may result from a variety of environmental challenges. To investigate whether the stress response, and in particular the HPI axis, in tilapia (Oreochromis mossambicus) is compromised by short-term exposure to PCB 126, fish of both sexes were fed diets containing PCB 126 (50 microg/kg fish . day) for 5 days. In the first approach, which was performed twice, fish were acutely stressed for periods varying between 1 and 30 min at the end of the exposure period; in the second approach fish were sampled at the end of the exposure period either at rest or after 2 h of stress (confinement). After 5 days, the body weights in all experiments were significantly lower in PCB-fed fish than in control fish. There were no changes in basal plasma glucose levels, plasma ion concentrations, or branchial, renal, and intestinal Na,K-ATPase activity following PCB exposure. In the first experimental approach, in which fish experienced acute sampling stress, plasma cortisol levels reached lower levels in PCB-fed fish than in controls. This suggests an impaired ability to acutely activate interrenal steroidogenesis in PCB-treated tilapia. Adrenocorticotropic hormone (ACTH)- and cAMP-stimulated in vitro cortisol release from superfused head kidneys was lower in tissues from tilapia exposed to PCB 126 than in tissues from control animals. This effect persisted after 24 h in vitro, which, together with the high PCB 126 concentrations measured in the head kidneys of PCB-fed fish, may indicate direct toxic effects on the interrenal cells. The second experimental approach demonstrated that basal plasma cortisol and ACTH levels were not influenced by PCB treatment, but that the basal ACTH content of the rostral pars distalis (RPD) of the pituitary gland of PCB-fed fish was lower than that of control fish. After 2 h confinement, plasma cortisol levels and ACTH content of the RPD rose to similar values in both groups, whereas plasma ACTH levels were higher in confined PCB-fed fish than in confined controls. PCB-fed fish showed a lower hyperglycemic response to confinement than control fish. Confinement resulted in similarly elevated renal and intestinal Na,K-ATPase activities in both PCB-fed and control fish; branchial enzyme activities were not affected. Since PCB did not affect Na,K-ATPase activities and plasma ion concentrations, it is concluded that the effects of PCB 126 on the HPI axis in tilapia are not secondary to ionoregulatory dysfunction.
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PMID:Interrenal stress responsiveness of tilapia (Oreochromis mossambicus) is impaired by dietary exposure to PCB 126. 940 23

Studies have shown that polychlorinated biphenyls may affect cognitive functions both in human and also in experimental animals. One of the neurochemical parameters that is changed after exposure to these compounds is a reduction in the dopamine level in the brain, although the mechanism behind this reduction is not known. We have therefore investigated whether this reduction could be caused by an effect on vesicular uptake. ortho-Chlorinated biphenyls are found to be competitive inhibitors of dopamine transport into synaptic vesicles from rat brain with K(i) concentrations as low as 4 microM. In contrast, several nonortho-chlorinated biphenyls did not inhibit vesicular uptake. The inhibition was specific for dopamine, in that the uptake of glutamate and GABA was inhibited at higher PCB concentrations under identical conditions. The vesicular Mg-ATPase proton pump was also inhibited at higher concentrations of PCBs than the dopamine transport. Uptake of methylamine gave no indication of any disruption of the vesicular proton gradient. The inhibition of dopamine vesicular uptake by PCBs was competitive. Several of the ortho-PCBs also inhibited the binding of tetrabenazine, which is known to bind to a site close to the dopamine binding site, at the vesicular transporter. The results show that inhibition of vesicular uptake may contribute to the decrease of dopamine reported in nervous tissue after exposure to PCBs under different conditions.
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PMID:The effect of polychlorinated biphenyls on the uptake of dopamine and other neurotransmitters into rat brain synaptic vesicles. 1062 Apr 85

Mitochondrial proteins and phospholipids were estimated and SDH, Na(+)-K(+)-ATPase and Mg(2+)-ATPase activities were analysed in the gill, liver and heart tissues of PCB 1232 (sublethal doses) treated fish A. caelatus. Protein and phospholipids were found to be decreased significantly and SDH, Na(+)-K(+)-ATPase, Mg(2+)-ATPase and other enzyme systems displayed an inverse relationship with PCB dosage. Statistical analysis was carried out to indicate the relationship between sublethal doses of varying concentration and the activities of the enzyme systems involved in energy metabolism. The studies indicated impairment in mitochondrial functions.
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PMID:Toxicity of PCB 1232 on mitochondria of fish Arius caelatus (Valenciennes). 1525 43

Only few data are available on the carcinogenic potency of individual PCB congeners. In this study, we tested the 'non-dioxinlike' congeners PCB 28 and 101 for their potency as liver tumor promoters in female rats which received diethyl-N-nitrosamine as an initiator. After 8 or 16 weeks of PCB treatment (50 and 150 micromol/kg body weight per week), each congener was recovered in the liver according to the dose levels applied, with PCB 28, at the same dose level, showing nine- to 16-fold higher hepatic levels than PCB 101 (approximately, 44 micromol/kg versus 5 micromol/kg liver at low dose, 145 micromol/kg versus 9 micromol/kg liver at high dose). PCB 28 was found to mildly induce hepatic EROD activity, while both congeners induced PROD activity. With each congener, no significant increase in the number of ATPase-deficient or GSTP-positive preneoplastic foci was obtained, while a significant increase in the relative hepatic volume of ATPase-deficient foci was found in the livers of DEN pre-treated animals having received 50 micromol/kg body weight of PCB 101 per week over 16 weeks. Our results revealed that neither the accumulative PCB 28 nor the more readily metabolisable PCB 101 was an efficacious tumor promoter in the livers of female rats.
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PMID:Tumor promoting potency of PCBs 28 and 101 in rat liver. 1642 74