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)

Since DDA [bis(p-chlorophenyl)acetic acid] has been shown to be transported and concentrated by the renal proximal tubule, this metabolite of DDT has been postulated to be a potential nephrotoxic agent. The present study explored the renal transport of DDA in the isolated, perfused rat kidney and the effects of DDA on renal function. When DDA (0.6 microM) was present in a dextran perfusate which eliminated DDA-colloid binding, the DDA/inulin clearance ratio was congruent to 0.05; however, some metabolism of DDA was apparent. During these studies, DDA had no effect on the glomerular filtration rate and the fractional reabsorption of Na, K or H2O. To determine the concentration of DDA which would produce an effect on renal cellular function, studies were performed with renal cortical slices. DDA at media concentrations greater than or equal to 0.1 mM were needed to produce significant alterations in tetraethylammonium transport, tissue oxygen consumption and intracellular electrolyte composition; however, no effect was demonstrated on Na-K-ATPase activity although DDA did affect Mg-ATPase activity. In conclusion, DDA at a 0.6 microM perfusate concentration undergoes net tubular reabsorption and metabolism without affecting the function of the perfused kidney. Only high concentrations of DDA were shown to produce alterations in cellular function.
 ...
PMID:Renal tubular transport and nephrotoxicity of DDA. 625 51

The effect of a single oral dose of pp'DDT (100 mg/kg body wt.) has been studied on the intestinal uptake of certain nutrients and on brush border enzymes in rats. Intestinal uptake of leucine, and phenylalanine was considerably increased but there was no change in the absorption of glucose and alanine in DDT fed rats, compared to controls. The activities of brush border sucrase, alkaline phosphatase and Na+, K+-ATPase were significantly depressed in pesticide treated animals, but leucine aminopeptidase levels remained unaffected under these conditions. Analysis of the chemical composition of the microvillus membranes revealed a considerable enhancement in total lipids, phospholipids and triglyceride contents of the membranes in DDT exposed rats, but membrane protein, sialic acid and cholesterol fractions did not record any change. 1-14C-acetate incorporation into various lipid classes was studied to explain the observed increase in membrane lipids in DDT exposed animals.
 ...
PMID:Effect of a single oral dose of pp'DDT on the absorption of nutrients in vitro and on brush border enzymes in rat intestine. 627 79

Efforts were made to understand the nature of the site of 1,1-bis-(p-chlorophenyl)-2,2,2-trichloroethane (DDT) inhibition of nerve ATPase. THe phospholipid content of nerve preparations from the walking leg of the lobster was reduced by treating them with phospholipase A, or with a chloroform-methanol mixture at -75 degrees. By these treatments the enzymes lost approximately 70 or 95% of their phospholipids and 50-80% of their Na,K- and Ca-ATPase activities. The lost ATPase activities could be partially restored by the addition of phospholipids, either the ones extracted from the lobster nerves or those from commercial sources. ATPase inhibition by DDT and permethrin was found to be highest in preparations where the phospholipids were removed by the above treatments, next highest with the untreated original enzyme, and least with the reconstituted ATPase regardless of the source of phospholipids used for reconstitution. This tendency was more pronounced in the case of Ca-ATPase. The effects of DDT and permethrin on inhibition of reconstituted Ca-ATPase were higher when the insecticide was first added to the protein portion and the enzyme was then reconstituted with the phospholipids, than when the same amount of insecticide was first added to the phospholipids which were then used for reconstitution.
 ...
PMID:Role of phospholipids in the inhibitory action of DDT and permethrin on the nerve ATPase of lobster, Homarus americanus. 628 78

Gossypol occurs naturally in the pigment glands in cotton. It has a role in protecting cotton plants from insect pests such as bollworms, yet it was not toxic to the cotton leafworm larvae Spodoptera littoralis up to 2-5% concentration in artificial diet or at 125 micrograms/ larva by topical application. The compound inhibited protease and lipid peroxidase activities in larvae with in vitro I50 values of 1.5 X 10(-3)M, and 4.4 X 10(-4)M respectively. When gossypol was fed to Spodoptera larvae, it stimulated the microsomal N-demethylase in vitro. This inductive effect was time-dependent similar to that of phenobarbital. Gossypol stimulates ATPase at lower concentrations and inhibited it at higher concentrations. The I50 for mitochondrial ATPase was 1.7 X 10(-4)M, while the corresponding values for DDT and fenvalerate were 1.1 X 10(-4)M and 7.0 X 10(-4)M respectively. Gossypol at 1.5% concentration in the diet reduced the larval weight to 50% of the control within two days, and increased the duration of each larval stage. The number of eggs and their hatchability was seriously decreased in larvae treated for three consecutive generations. Such an effect can be attributed to the ability of gossypol to interfere with protein bio-synthesis.
 ...
PMID:Gossypol as an inducer or inhibitor in Spodoptera littoralis larvae. 645 17

1. The effects of the specific protein kinase C (PKC) inhibitor, GF109203X, were measured on the cytoplasmic Ca2+ concentration ([Ca2+]i), and on histamine H1 receptor- and thapsigargin-mediated increases in [Ca2+]i in DDT1 MF-2 smooth muscle cells. 2. After pretreatment of cells with GF109203X (5 microM, 45 min), the histamine (100 microM)-induced initial rise in [Ca2+]i, representing Ca2+ mobilization from internal stores, was inhibited (by 59 +/- 7%). The slowly declining phase of the histamine induced Ca2+ response, reflecting Ca2+ entry, was enhanced (83 +/- 26%) in the presence of the PKC inhibitor. 3. The histamine induced release of Ca2+ from internal stores, measured after blocking Ca2+ entry with LaCl3 was inhibited by GF109203X in a concentration-dependent manner (IC50: 3.1 +/- 1.1 microM). 4. Histamine-induced formation of inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) was not changed in the presence of GF109203X. 5. The PKC activating phorbol ester, phorbol 12-myristate 13-acetate (PMA, 1 microM), strongly reduced histamine-induced Ins(1,4,5)P3 formation (58 +/- 16%). This effect was reversed by GF109203X (5 microM). Furthermore, PMA diminished histamine evoked Ca2+ release (50 +/- 6%) and blocked Ca2+ entry completely. 6. The rise in [Ca2+]i caused by blocking endoplasmic reticulum Ca2(+)-ATPase with thapsigargin (1 microM), was strongly reduced (57 +/- 3%) after pretreatment of cells with GF109203X. Downregulation of PKC by long-term pretreatment of cells with PMA (1 microM, 48 h) did not abolish this effect of GF109203X (48 +/- 3% inhibition). 7. In permeabilized DDT, MF-2 cells preloaded with 45Ca2+ in the presence of GF109203X, the amount of 45Ca2+ released by Ins(1,4,5)P3 (10 microM) was markedly reduced (42 +/- 9%). GF109203X did not release Ca2+ itself and did not impair Ins(1,4,5)P3 receptor function. 8. Uptake of 45Ca2+ by intact cells, representing Ca2+ entry, was enhanced by GF109203X (65 +/- 11%), by histamine (24 +/- 6%) and also by thapsigargin (121 +/- 10%). The GF109203X- and the thapsigargin-induced uptake of 45Ca2+ were not additive. 9. These data suggest that GF109203X reduces the filling-state of intracellular Ins(1,4,5)P3 sensitive Ca2+ stores by inhibiting the Ca2+ uptake into these stores, thereby promoting store-dependent (capacitive) Ca2+ entry.
 ...
PMID:The effect of the PKC inhibitor GF109203X on the release of Ca2+ from internal stores and Ca2+ entry in DDT1 MF-2 cells. 890 48

The effects of DDE (2,2-bis(p-chlorophenyl)-1,1-dichloroethylene), the major metabolite of DDT (2,2-bis(p-chlorophenyl)-1,1,1-trichloroethane), on rat liver mitochondrial bioenergetic activities were examined. The approach developed by M. D. Brand (Biochim Biophys Acta 1018: 128-133, 1990) was used to assess the effects of DDE because it is possible to discriminate the sites of action of compounds having pleiotypic effects on oxidative phosphorylation. Data were further confirmed using a "classical" approach, including measurements of transmembrane potential, respiratory indexes, enzymatic activities and membrane permeability to protons. DDE up to 40 nmol/mg protein affected the proton motive force generating system. In fact, DDE interacted with succinate dehydrogenase (complex II), decreasing respiration and membrane potential. In this concentration range, the permeability of the inner membrane to protons remained intact. Only higher concentrations (> or = 80 nmol/mg) increased permeability to protons, uncoupling oxidation from phosphorylation. The phosphorylative system was not affected because the rate of ATP synthesis was unchanged. In addition, data from carbonyl cyanide m-chlorophenylhydrazone-uncoupled rotenone-inhibited preparations or submitochondrial particles indicated that F0F1 ATPase activity is not affected by DDE. Therefore, DDE inhibition of complex II and putative inhibition of succinate translocation explain the depression of mitochondrial respiration. The use of appropriate substrates and assay conditions indicates that complexes I, III and IV were not affected by DDE. The uncoupling of oxidative phosphorylation at high concentrations (> 80 nmol DDE/mg protein) was probably related to deleterious effects on the integrity of the mitochondrial membrane. We confirmed that the technique originally proposed by Brand is useful for characterizing the effects of xenobiotics on oxidative phosphorylation. In addition, data provided by this technique closely agree with data from classical studies.
 ...
PMID:Interactions of 2,2-bis(p-chlorophenyl)-1,1-dichloroethylene with mitochondrial oxidative phosphorylation. 906 33

High levels of resistance to thapsigargin (TG), a specific inhibitor of intracellular Ca2+ transport ATPases (SERCAs), can be developed in culture by stepwise exposure of mammalian cells to increasing concentrations of TG. We have identified, in two independently selected TG-resistant hamster cell lines of different lineages, mutant forms of SERCA. In the TG-resistant Chinese hamster lung fibroblast cell line DC-3F/TG, a T --> C change at nucleotide 766 introduces a Phe256 --> Leu alteration within the first cytosolic loop of the SERCA. In contrast, in the TG-resistant Syrian hamster smooth muscle cell line DDT/TG 4 microM, a T --> C change at nucleotide 767 introduces a Phe256 --> Ser mutation at that position. When these specific mutations are introduced into a wild-type full-length avian SERCA1 cDNA, transfection experiments reveal that Ca2+ transport function and ATP hydrolytic activity are not altered by such mutations. However, a 4-5-fold resistance to TG inhibition of Ca2+ transport function occurs upon the introduction of either the Phe256 --> Leu or the Phe256 --> Ser mutation into wild-type SERCA1. These specific mutations also render the hydrolytic activity of the ATPase resistant to inhibition by TG. Our results not only implicate amino acid 256 in TG-SERCA interactions, but also demonstrate that specific mutations within SERCA can mediate resistance to TG.
 ...
PMID:Specific substitutions at amino acid 256 of the sarcoplasmic/endoplasmic reticulum Ca2+ transport ATPase mediate resistance to thapsigargin in thapsigargin-resistant hamster cells. 945 80

In the present study the effects of organochlorine pesticides: o,p'-DDT, p,p''-DDT, methoxychlor, and lindane on ATPase activities of microsomal fractions of bovine oviductal and endometrial cells were investigated. We were not able to characterize a Ca2+ stimulated ATPase, whereas 57 and 15% of the total ATPase activity were sensitive to Mg2+ in the oviductal and endometrial fractions, respectively. After 10 min preincubation with the four organochlorines, a significant inhibition was found only with o,p''-DDT at 32 microM (27.9%) and 64 microM (35.6%) in the oviductal microsomal fraction and at 64 microM (32.2%) in that of the endometrium. Increasing the preincubation time to 30 min, the Mg2+ ATPase in the endometrial fraction was significantly inhibited by all four pesticides at 64 microM, but in the oviductal fraction only at 64 microM o,p''-DDT. It is suggested that organochlorine pesticides can have an influence on cells responsible for reproduction.
 ...
PMID:Influence of organochlorine pesticides on ATPase activities of microsomal fractions of bovine oviductal and endometrial cells. 1004 52

1,1-bis-(p-Chlorophenyl)-2,2,2-trichloroethane (DDT) inhibited the ATP hydrolytic activity of the ATP synthase from a DDT-susceptible insect (Apis mellifera) as well as a DDT-tolerant insect (Spodoptera littoralis), and from rat liver and bovine heart in a parallel way to its insecticidal properties and selectivity of action. Inhibition of the ATPase activity of these preparations by DDT was parallel to the poisoning of the source organism with DDT. Furthermore, both the inhibition and poisoning of insects were affected similarly by temperature. Inhibition of the insect enzyme activity by DDT was specific and differed from that by oligomycin or N,N-dicyclohexylcarbodi-imide (DCCD). PAGE analysis of the various preparations of the enzyme showed that the inhibition of the enzyme activity by DDT was associated with the presence of a selective protein band with an apparent molecular mass of 23 kDa. This protein band exists in the preparations from the DDT-susceptible insects but was absent from the preparations of the enzyme from the DDT-insensitive sources. Removal of this protein band from the enzyme rendered its activity insensitive to inhibition by DDT. The protein was purified directly from mitochondria and the DDT sensitivity was reconstituted upon its addition to the DDT-insensitive F1-ATPase. We conclude that this identified protein of the ATP synthase is the DDT target protein in insects.
 ...
PMID:Resolving the DDT target protein in insects as a subunit of the ATP synthase. 1183 25

ACF is a chromatin-remodeling complex that catalyzes the ATP-dependent assembly of periodic nucleosome arrays. This reaction utilizes the energy of ATP hydrolysis by ISWI, the smaller of the two subunits of ACF. Acf1, the large subunit of ACF, is essential for the full activity of the complex. We performed a systematic mutational analysis of Acf1 to elucidate the functions of specific subregions of the protein. These studies revealed DNA- and ISWI-binding regions that are important for the chromatin assembly and ATPase activities of ACF. The DNA-binding region of Acf1 includes a WAC motif, which is necessary for the efficient binding of ACF complex to DNA. The interaction of Acf1 with ISWI requires a DDT domain, which has been found in a variety of transcription and chromatin-remodeling factors. Chromatin assembly by ACF is also impaired upon mutation of an acidic region in Acf1, which may interact with histones during the deposition process. Lastly, we observed modest chromatin assembly defects on mutation of other conserved sequence motifs. Thus, Acf1 facilitates chromatin assembly via an N-terminal DNA-binding region with a WAC motif, a central ISWI-binding segment with a DDT domain, and a C-terminal region with an acidic stretch, a WAKZ motif, PHD fingers, and bromodomain.
 ...
PMID:Binding of Acf1 to DNA involves a WAC motif and is important for ACF-mediated chromatin assembly. 1219 34


<< Previous 1 2 3 4 Next >>