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 respiratory deficiency of two noncomplementing mutants of Saccharomyces cerevisiae (C41 and N28) has been shown to be due to mutations in HEM2, the structural gene for delta-aminolevulinate dehydratase. The mutants are unable to convert delta-aminolevulinic acid to porphobilinogen and are not complemented by the hem2 mutant GL4 (Gollub, E. G., Liu, K.-P., Dagan, J., Adlersberg, M., and Sprinson, D. B. (1977) J. Biol. Chem. 252, 2846-2854). A gene capable of complementing the respiratory deficiency of C41 and N28 has been cloned by transformation of a hem2 mutant with a recombinant plasmid library of wild type yeast nuclear DNA. The sequence of the protein encoded by the cloned gene exhibits extensive homology to the recently reported sequence of human delta-aminolevulinate dehydratase (Wetmur, J. G., Bishop, D. F., Cantelmo, C., and Desnick, R. J. (1986) Proc. Natl. Acad. Sci. U. S. A. 83, 7703-7707). Several approaches were taken to study the effect of heme on transcription of PET genes known to code for subunit components of respiratory enzymes and of mitochondrial ATPase. The first involved measurements of the steady state levels of mRNAs for subunit 5 of cytochrome oxidase and the beta subunit of F1 ATPase in wild type and in a hem2 mutant. Secondly, transcription of the genes coding for the cytochrome oxidase and ATPase subunits as well as of the COR1 gene coding for the 44-kDa core 1 subunit of coenzyme QH2-cytochrome c reductase was quantitated by fusing the 5'-flanking and part of the coding region of each gene to the lacZ gene of Escherichia coli in vectors capable of integrating into yeast chromosomal DNA. The different lacZ fusions were integrated into nuclear DNA of a wild type strain and of hem2 mutants allowing expression of beta-galactosidase to be studied as a function of intracellular heme. These experiments indicate that the promoters of the genes for subunits of the respiratory complexes are regulated by heme. In contrast, the expression of the ATPase subunit appears to be heme-independent. Because neither subunit 5 of cytochrome oxidase nor the core 1 subunit of coenzyme QH2-cytochrome c reductase are hemoproteins, transcriptional regulation by heme may be a general mechanism for controlling the synthesis of mitochondrial proteins involved in respiration.
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PMID:Characterization of the yeast HEM2 gene and transcriptional regulation of COX5 and COR1 by heme. 244 51

One-day old American kestrel (Falco sparverius) nestlings were orally dosed daily with 5 microliters/g of corn oil (controls), 25, 125 or 625 mg/kg of metallic lead in corn oil for 10 days. Forty per cent of the nestlings receiving 625 mg/kg of lead died after 6 days and growth rates were significantly depressed in the two highest lead dosed groups. At 10 days hematocrit values were significantly lower in the two highest lead treated groups, and hemoglobin content and red blood cell delta-aminolevulinic acid dehydratase (ALAD) activity was depressed in all lead treated groups. Plasma creatine phosphokinase decreased in the two highest treatment groups. Brain, liver and kidney ALAD activities, brain RNA to protein ratio and liver protein concentration decreased after lead exposure whereas liver DNA, DNA to RNA ratio and DNA to protein ratio increased. Brain monoamine oxidase and ATPase were not significantly altered. Measurements of the ontogeny of hematological variants and enzymes in normal development, using additional untreated nestlings, revealed decreases in red blood cell ALAD, plasma aspartate amino transferase, lactate dehydrogenase, brain DNA and RNA and liver DNA, whereas hematocrit, hemoglobin, plasma alkaline phosphatase, brain monoamine oxidase, brain ALAD and liver ALAD increased during the first 10 days of posthatching development. Biochemical and hematological alterations were more severe than those reported in adult kestrels or precocial young birds exposed to lead. Alterations may be due in part to delayed development.
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PMID:Biochemical and hematological effects of lead ingestion in nestling American kestrels (Falco sparverius). 286 Oct 31

Following boron intake, multiple effects have been observed in animal experiments. However, human data is lacking, and no data is available on the ability of boron to accumulate in fetal tissues. Positive responses in animal species suggest that developmental toxicity may be an area of concern in humans, following exposure to boron. Two hypotheses have seemed to account for the multiple effects described in scientific findings. One hypothesis is that boron is a negative regulator that influences a number of metabolic pathways by competitively inhibiting some key enzyme reactions. The other hypothesis is that boron has a role in ionic membrane transport regulations. To better understand boron potential toxicity, the present study examined the relationship between boron exposure and some key enzymes, well-known for their affinity for mineral elements, such as delta-aminolevulinic acid dehydratase (ALA-D), and two fundamental enzymes having a role in ionic membrane transport regulations (Ca-pump and Na(+)K(+)-ATPase). We investigated the potential effects of an environmental boron exposure on the activity of these enzymes in an urban population of 197 "normal" newborns. Environmental boron exposure was assessed in placental tissue. Because of the well-known inhibiting effect of lead on these enzymes, cord blood and placental lead were also analyzed. After adjustment for potential confounders, including lead, placental boron levels were negatively significantly correlated to ALA-D activity while Ca-pump and Na(+)K(+)-ATPase activities did not seem to be affected by the level of boron exposure. Given boron's ability, as a Lewis acid, to complex with hydroxyl groups, we suggest that such a mechanism would explain the inhibiting effect of boron on ALA-D.
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PMID:Environmental boron exposure and activity of delta-aminolevulinic acid dehydratase (ALA-D) in a newborn population. 1514 Oct 99

This study examined the impact of elevated dietary Ca(2+) on the responses to chronic dietary Pb exposure in juvenile rainbow trout. Trout were fed reference (0.3microgPb/g, approximately 20mgCa(2+)/g) and Pb-enriched diets ( approximately 50 or 500microgPb/g) in the presence of background Ca(2+) ( approximately 20mgCa(2+)/g) or ( approximately 60mgCa(2+)/g) of added Ca(2+) (as CaCO(3)) for 42 days. The quantitative order of Pb accumulation in tissues reflected the exposure pathway of Pb via the diet (per tissue wet weight): gut>bone>kidney>liver>spleen>gill>carcass>brain>white muscle. The anterior intestine accumulated the most Pb per tissue wet weight, while the bone accumulated the most Pb per fish weight. Pb concentrations were much higher in the posterior kidney than the anterior kidney. Simultaneous addition of Ca(2+) to the diet had an overall protective effect in all the tissues analysed in reducing Pb accumulation. The RBCs accumulated 100 times more Pb when compared to the plasma, while the whole blood delta-aminolevulinic acid dehydratase was inhibited in the high treatment group without added Ca(2+), by the end of the exposure. Neither plasma Cl(-), K(+), Mg(2+) nor Na(+), K(+)-ATPase activities in the gills, mid- and posterior intestine were affected. However, there were mild disruptions in plasma Na(+) and Ca(2+) levels in the elevated Pb and Ca(2+) treatment groups, and a significant up-regulation in Na(+), K(+)-ATPase activity at the anterior intestine in fish fed the high Pb diets with background or added Ca(2+). By day 42, Pb levels in most tissues had either stabilized or started to decrease, indicating some capacity for regulation of accumulated loads. We conclude that elevated dietary Ca(2+) levels will be protective in reducing Pb burdens in freshwater juvenile rainbow trout exposed to environments contaminated with waterborne Pb.
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PMID:The chronic effects of dietary lead in freshwater juvenile rainbow trout (Oncorhynchus mykiss) fed elevated calcium diets. 1663 Jun 65

In the present study the potential neurotoxicity of diphenyl diselenide, as measured by the manifestation of seizures in rat pups (postnatal days, PND, 12-14) was evaluated. The results suggest that the latency for the appearance of tonic-clonic seizures, characterized by rearing and falling of rat pups body, was dependent of the dose tested. Diphenyl diselenide at high doses induced seizure episodes in rat pups. The highest dose of diphenyl diselenide (500 mg/kg) increased the levels of lipid peroxidation and catalase activity as well as decreased delta-ALA-D (delta-aminolevulinate dehydratase) and Na(+), K(+) ATPase activity in the brain of rat pups. Our results indicate the possible involvement of free radical oxygen injury in diphenyl diselenide-induced seizures. The data obtained with the dose of 150 mg/kg in the brain of rats that exhibited seizures are: an increase in lipid peroxidation levels; the lack of effect on catalase activity; an inhibition of delta-ALA-D activity, supporting that the enzyme activity is more sensitive than other parameters analyzed as an indicator of oxidative stress. The lowest dose of diphenyl diselenide emphasizes the relationship between the appearance of seizures and the latency for the onset of the first episode. Taken together, this paper could add to our understanding of diphenyl diselenide neurotoxic effect demonstrated by the appearance of seizures which are, at least in part, related to the oxidative stress.
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PMID:Involvement of oxidative stress in seizures induced by diphenyl diselenide in rat pups. 1732 Aug 26

The present study sought to evaluate the effect of a newly synthesized selenium compound, dicholesteroyl diselenide (DCDS) and diphenyl diselenide (DPDS) on the activities of delta-aminolevulinate dehydratase and Na+/K+-ATPase in the rat brain. The glutathione peroxidase mimetic activity of the two compounds as well as their ability to oxidize mono- and di- thiols were also evaluated. The antioxidant effects were tested by measuring the ability of the compounds to inhibit the formation of thiobarbituric acid reactive species and also their ability to inhibit the formation of protein carbonyls. The results show that DPDS exhibited a higher glutathione peroxidase mimetic activity as well as increased ability to oxidize di-thiols than DCDS. In addition, while DPDS inhibited the formation of thiobarbituric acid reactive species and protein carbonyls, DCDS exhibited a prooxidant effect in all the concentration range (20-167 microM) tested. Also the activities of cerebral delta-aminolevulinate dehydratase and Na+/K+ ATPase were significantly inhibited by DPDS but not by DCDS. In addition, the present results suggested that the inhibition of Na+/K+ ATPase by organodiselenides, possibly involves the modification of the thiol group at the ATP binding site of the enzyme. In conclusion, the results of the present investigation indicated that the non-selenium moiety of the organochalcogens can have a profound effect on their antioxidant activity and also in their reactivity towards SH groups from low-molecular weight molecules and from brain proteins.
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PMID:Comparative studies on dicholesteroyl diselenide and diphenyl diselenide as antioxidant agents and their effect on the activities of Na+/K+ ATPase and delta-aminolevulinic acid dehydratase in the rat brain. 1771 May 41

This study was designed to examine if diphenyl diselenide (PhSe)(2), an organoselenium compound, attenuates pulmonar and cerebral oxidative stress caused by sub-chronic exposure to CdCl(2). Male adult Swiss albino mice received CdCl(2) (10 micromol/kg, subcutaneously), 5 times/week, for 4 weeks. (PhSe)(2) (10 micromol/kg or 20 micromol/kg, orally) was given concomitantly with CdCl(2) to mice. A number of toxicological parameters in lung and brain of mice were examined including delta-aminolevulinic acid dehydratase (delta-ALA-D), superoxide dismutase (SOD) and catalase activities, lipid peroxidation, non-protein thiols (NPSH) and ascorbic acid content. Na(+),K(+)-ATPase activity, acetylcholinesterase (AChE) activity, [(3)H]glutamate uptake and [(3)H]glutamate release were also carried out in brain. Cadmium concentration and histopathological analysis were carried out in lung tissue. (PhSe)(2) at the dose of 20 micromol/kg protected the inhibition of delta-ALA-D, SOD and CAT activities, the reduction of vitamin C content and the increase of lipid peroxidation levels caused by CdCl(2) in lungs. At 10 micromol/kg, (PhSe)(2) protected cerebral AChE and CAT activities inhibited by CdCl(2). There were no histopathological alterations in the lung of mice after CdCl(2) exposure. The pulmonary cadmium concentration was higher (2.8-fold) in the group exposed to CdCl(2) than in control mice. (PhSe)(2) at dose of 20 micromol/kg reduced cadmium concentration towards the control level. The results suggest that oral administration of (PhSe)(2) attenuated the oxidative damage induced by CdCl(2) in lung and brain of mice.
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PMID:Efficacy of diphenyl diselenide against cerebral and pulmonary damage induced by cadmium in mice. 1782 62

The aim of this study was to investigate the effects caused by subchronic exposure to diphenyl diselenide in rats. Adult Wistar rats were exposed to diphenyl diselenide (5-300 micromol kg(-1), subcutaneously) once a day for 14 days. The subchronic administration of diphenyl diselenide at a dose of 300 micromol kg(-1) significantly increased aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities in plasma. Conversely, this exposure did not alter lactate dehydrogenase (LDH) activity, urea and creatinine levels in plasma. The activity of delta-aminolevulinate dehydratase (delta-ALA-D) from liver and kidney was inhibited by high dosages of diphenyl diselenide. Diphenyl diselenide did not alter renal Na(+)/K(+)ATPase. A decline in body weight gain was associated with a decrease in food consumption in rats treated with 100 or 300 micromol kg(-1) diphenyl diselenide. At these dosages (100 and 300 micromol kg(-1)), diphenyl diselenide did not cause histological alterations in the liver of rats. Taken together, these results demonstrated that subchronic exposure to diphenyl diselenide at high doses induced minor toxicological effects.
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PMID:Toxicological evaluation of subchronic exposure to diphenyl diselenide in rats. 1797 52

In this study we evaluated the effect of diphenyl diselenide (PhSe)(2) on glycerol-induced acute renal failure in rats. Rats were pre-treated by gavage every day with (PhSe)(2 )(7.14 mg kg(-1)) for 7 days. On the eighth day, rats received an intramuscular injection of glycerol (8 mL kg(-1)). Twenty-four hours afterwards, rats were euthanized and the levels of urea and creatinine were measured in plasma. Catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST), delta-aminolevulinate dehydratase (delta-ALA-D) and Na(+), K(+)-ATPase activities and ascorbic acid levels were evaluated in renal homogenates. Histopathological evaluations were also performed. The results demonstrated that (PhSe)(2) was able to protect against the increase in urea and creatinine levels and histological alterations in kidney induced by glycerol. (PhSe)(2) protected against the inhibition in delta-ALA-D, CAT and GPx activities and the reduction in ascorbic acid levels induced by glycerol in kidneys of rats. In conclusion, the present results indicate that (PhSe)(2) was effective in protecting against acute renal failure induced by glycerol.
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PMID:Diphenyl diselenide protects against glycerol-induced renal damage in rats. 1948 1

Toxicological and pharmacological studies demonstrated that the introduction of functional groups into the aromatic ring of diphenyl diselenide alter its effect. The aim of this study was to evaluate the in vitro effect of m-trifluoromethyl-diphenyl diselenide (m-CF(3)-C(6)H(4)Se)(2), p-chloro-diphenyl diselenide (p-Cl-C(6)H(4)Se)(2) and p-methoxyl-diphenyl diselenide (p-CH(3)O-C(6)H(4)Se)(2) on delta-aminolevulinate dehydratase (delta-ALA-D) and Na(+), K(+)-ATPase activities in rat brain homogenates. Diselenides inhibited delta-ALA-D activity (IC(50) 4-6 microM [concentration inhibiting 50%]), and dithiothreitol (DTT) restored the enzyme activity. ZnCl(2) (100 microM) did not restore delta-ALA-D inhibition caused by (p-Cl-C(6)H(4)Se)(2) and (m-CF(3)-C(6)H(4)Se)(2). Na(+), K(+)-ATPase activity was more sensitive to (p-Cl-C(6)H(4)Se)(2) and (m-CF(3)-C(6)H(4)Se)(2) (IC(50) 6 microM) than (p-CH(3)O-C(6)H(4)Se)(2) and (PhSe)(2) (IC(50) 45 and 31 microM, respectively). DTT restored the activity of Na(+), K(+)-ATPase inhibited by diselenides. The effect of diselenides on Na(+)/K(+)-ATPase is dependent on their substitutions in the aromatic ring. The mechanism through which diselenides inhibit delta-ALA-D and Na(+), K(+)-ATPase activities involves the oxidation of thiol groups.
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PMID:Disubstituted diaryl diselenides inhibit delta-ALA-D and Na+, K+-ATPase activities in rat brain homogenates in vitro. 1950 2


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