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)

Cockayne's syndrome (CS) is a disease characterized by developmental and growth defects, sunlight sensitivity, and a defect in transcription-coupled nucleotide excision repair. The two principle proteins involved in CS, CSA and CSB/ERCC6, have been hypothesized to bind RNA polymerase II (Pol II) and link transcription to DNA repair. We have tested CSA and CSB in assays designed to determine their role in transcription-coupled repair. Using a unique oligo(dC)-tailed DNA template, we provide biochemical evidence that CSB/ERCC6 interacts with Pol II molecules engaged in ternary complexes containing DNA and nascent RNA. CSB is a DNA-activated ATPase, and hydrolysis of the ATP beta-gamma phosphoanhydride bond is required for the formation of a stable Pol II-CSB-DNA-RNA complex. Unlike CSB, CSA does not directly bind Pol II.
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PMID:Recruitment of the putative transcription-repair coupling factor CSB/ERCC6 to RNA polymerase II elongation complexes. 937 11

The objective of this study was to analyse the effects of isoflurane anesthesia (lasting for 15 or 60 min) and isoflurane anesthesia termination (after 1 or 24 h) on met-enkephalin (MENK) and leu-enkephalin (LENK) levels in discrete brain areas and spinal cord segments in rabbits. Moreover histochemical analysis of activities of succinate dehydrogenase, magnesium-dependent adenosine triphosphatase (Mg++ATP-ase) and acid phosphatase in the striatum and hypothalamus were carried out to evaluate the effects of isoflurane anesthesia on energetic, transport and catabolic processes. Throughout anesthesia (15 and 60 min) and after its termination (1 h) the LENK contents were increased in hypothalamus, hippocampus, mesencephalon and lumbar segment of spinal cord. Moreover, during isoflurane anesthesia and after its termination (1 h) MENK and LENK levels decreased in cervical segment and MENK content dropped in thoracic segment of spinal cord. Histochemical data indicated, that isoflurane enhanced energetic processes as well as exchange processes in neurocytes, glial cells, capillary walls and ependymal cells of the third ventricle. Measurements of acid phosphatase activity provided evidence of no signs of toxicity of isoflurane in the examined areas. The changes in enkephalin levels observed during the isoflurane anesthesia and after its termination depended on the type of examined neuropeptides, as well as on parts of the brain and spinal cord studied. The changes observed after isoflurane administration in enkephalinergic system are discussed with regard to our earlier experiments with halothane and enflurane.
Pol J Pharmacol
PMID:Influence of isoflurane on enkephalin levels and on some indicatory enzymes in the central nervous system of rabbits. 943 56

The influence of thapsigargin, a selective inhibitor of sarcoplasmic reticulum (SR) Ca2+ ATPase, on the positive inotropic effects of digoxin before and after pretreatment with rimalkalim [(3S,4R)-3-hydroxy-2,2-dimethyl-4-(oxopyrrolidinyl)-6-phenyl-su lfonylchroman hemihydrate (formerly HOE 234)], a known activator of ATP-sensitive K+ channels, was studied in the guinea pig heart. The isolated papillary muscles from the guinea pig heart were used to study these effects. The following parameters were measured: force of contraction (Fc), rate of rise (+dF/dt) and rate of fall (-dF/dt) of Fc, time to peak contraction (ttp) and time to 10% of the total amplitude of force (tt10). After pretreatment with rimalkalim (1 microM), digoxin caused a significant increase in the amplitude of Fc and significant shortening of ttp and tt10 (p < 0.05 compared with the values obtained with digoxin alone). Thapsigargin (1 microM), a selective inhibitor of sarcoplasmic reticulum Ca2+ ATPase, added to rimalkalim, prevented the enhancement of the amplitude of Fc induced by digoxin after pretreatment with rimalkalim but had no significant influence on the effects of digoxin itself. The results demonstrate significant influence of activation of KATP channels on digoxin-induced positive inotropic effects in the guinea pig heart. Attenuation of this effects of rimalkalim by addition of thapsigargin suggests that activation of SR Ca2+ ATPase can be included in this interaction.
Pol J Pharmacol
PMID:Thapsigargin attenuates the potentiation of positive inotropic effect of digoxin induced by pretreatment with rimalkalim in the guinea pig heart. 956 46

Physical interactions of simian virus 40 (SV40) large tumor (T) antigen with cellular DNA polymerase alpha-primase (Pol/Prim) and replication protein A (RPA) appear to be responsible for multiple functional interactions among these proteins that are required for initiation of viral DNA replication at the origin, as well as during lagging-strand synthesis. In this study, we mapped an RPA binding site in T antigen (residues 164 to 249) that is embedded within the DNA binding domain of T antigen. Two monoclonal antibodies whose epitopes map within this region specifically interfered with RPA binding to T antigen but did not affect T-antigen binding to origin DNA or Pol/Prim, ATPase, or DNA helicase activity and had only a modest effect on origin DNA unwinding, suggesting that they could be used to test the functional importance of this RPA binding site in the initiation of viral DNA replication. To rule out a possible effect of these antibodies on origin DNA unwinding, we used a two-step initiation reaction in which an underwound template was first generated in the absence of primer synthesis. In the second step, primer synthesis was monitored with or without the antibodies. Alternatively, an underwound primed template was formed in the first step, and primer elongation was tested with or without antibodies in the second step. The results show that the antibodies specifically inhibited both primer synthesis and primer elongation, demonstrating that this RPA binding site in T antigen plays an essential role in both events.
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PMID:The replication protein A binding site in simian virus 40 (SV40) T antigen and its role in the initial steps of SV40 DNA replication. 981 12

The influence of exogenous inorganic pyrophosphate on the transport of oleanolic acid monoglucoside and monoglucuronide to vacuoles isolated from Calendula officinalis leaf protoplasts was studied. The results indicate that the transport of both monoglycosides is carrier-mediated; however, the transport of the monoglucuronide is passive, and that of the monoglucoside active. The active transport of the monoglucoside is dependent on tonoplast energization created as a result of cooperation of two vacuolar proton pumps: H+-ATPase and H+-PPase.
Acta Biochim Pol 1998
PMID:The effect of inorganic pyrophosphate on the transport of oleanolic acid monoglycosides into vacuoles isolated from Calendula officinalis leaves. 991 10

The aim of this study was to evaluate the effect of 5-, 15-, and 60-min enflurane anesthesia on the levels of Met-enkephalin, Leu-enkephalin and neuropeptide Y in discrete areas of the rabbit brain. We also evaluated the effect of enflurane anesthesia on energetic, transport and catabolic processes by measuring the activities of succinate dehydrogenase, magnesium-dependent adenosine triphosphatase and acid phosphatase in the rabbit striatum and hypothalamus. Induction of anesthesia (5 min) decreased Met-enkephalin levels in the hypothalamus and striatum, and increased them in the hippocampus and mesencephalon. Induction of anesthesia increased Leu-enkephalin levels in all brain areas studied, except for the striatum, and increased neuropeptide Y content in the hippocampus. 15- and 60-min enflurane anesthesia increased Met-enkephalin content in the hypothalamus and hippocampus. After 15- and 60-min anesthesia, and after cessation of anesthesia, Leu-enkephalin levels were increased in the hypothalamus and mesencephalon, and were decreased in the striatum and hippocampus. In the striatum, neuropeptide Y content was significantly decreased during anesthesia and after cessation of anesthesia. Histochemical analysis revealed that enflurane enhanced ATP production, catabolic processes, and the rates of exchange and transport of energetic substrates in the striatum and hypothalamus. In conclusion, enflurane affects the levels of Met, Leu-enkephalins and NPY in a manner depending on the duration of anesthesia and the brain structure. Compared with isoflurane , which was studied in our previous study enflurane produces stronger alterations in the activities of enzymatic marker in the rabbit brain. This suggests that enflurane may be less safe than isoflurane.
Pol J Pharmacol
PMID:Effect of enflurane on selected neuropeptides and marker enzymes in rabbit brain. 1009 16

Mutations in the gene for the conserved, essential nuclease-helicase Dna2 from the yeast Saccharomyces cerevisiae were found to interact genetically with POL1 and CTF4, which encode a DNA Polymerase alpha subunit and an associated protein, suggesting that Dna2 acts in a process that involves Pol alpha. DNA2 alleles were isolated that cause either temperature sensitivity, sensitivity to alkylation damage, or both. The alkylation-sensitive alleles clustered in the helicase domain, including changes in residues required for helicase activity in related proteins. Additional mutations known or expected to destroy the ATPase and helicase activities of Dna2 were constructed and found to support growth on some media but to cause alkylation sensitivity. Only damage-sensitive alleles were lethal in combination with a ctf4 deletion. Full activity of the Dna2 helicase function is therefore not needed for viability, but is required for repairing damage and for tolerating loss of Ctf4. Arrest of dna2 mutants was RAD9 dependent, but deleting this checkpoint resulted in either no effect or suppression of defects, including the synthetic lethality with ctf4. Dna2 therefore appears to act in repair or lagging strand synthesis together with Pol alpha and Ctf4, in a role that is optimal with, but does not require, full helicase activity.
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PMID:Dna2 mutants reveal interactions with Dna polymerase alpha and Ctf4, a Pol alpha accessory factor, and show that full Dna2 helicase activity is not essential for growth. 1010 Nov 69

In hepatocellular carcinoma HepG2 cells, free polymannose-type oligosaccharides appearing in the cytosol during the biosynthesis and quality control of glycoproteins are rapidly translocated into lysosomes by an as yet poorly defined process (Saint-Pol, A., Bauvy, C., Codogno, P., and Moore, S. E. H. (1997) J. Cell Biol. 136, 45-59). Here, we demonstrate an ATP-dependent association of [2-3H]mannose-labeled Man5GlcNAc with isolated rat liver lysosomes. This association was only observed in the presence of swainsonine, a mannosidase inhibitor, which was required for the protection of sedimentable, but not nonsedimentable, Man5GlcNAc from degradation, indicating that oligosaccharides were transported into lysosomes. Saturable high affinity transport (Kuptake, 22.3 microM, Vmax, 7.1 fmol/min/unit of beta-hexosaminidase) was dependent upon the hydrolysis of ATP but independent of vacuolar H+/ATPase activity. Transport was inhibited strongly by NEM and weakly by vanadate but not by sodium azide, and, in addition, the sugar transport inhibitors phloretin, phloridzin, and cytochalasin B were without effect on transport. Oligosaccharide import did not show absolute specificity but was selective toward partially demannosylated and dephosphorylated oligosaccharides, and, furthermore, inhibition studies revealed that the free reducing GlcNAc residue of the oligosaccharide was of critical importance for its interaction with the transporter. These results demonstrate the presence of a novel lysosomal free oligosaccharide transporter that must work in concert with cytosolic hydrolases in order to clear the cytosol of endoplasmic reticulum-generated free oligosaccharides.
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PMID:Cytosol-to-lysosome transport of free polymannose-type oligosaccharides. Kinetic and specificity studies using rat liver lysosomes. 1022 24

The discovery of opioid receptors and endogenous substances capable of specific binding to these receptors, i.e. endorphin and enkephalin, is one of the most spectacular indications suggesting that the presence of a receptor for a certain drug in the organism authenticates searching for an endogenous substances with high affinity at this receptor. Later, further studies were undertaken to detect other endogenous drug-like factors. Some experiments led to the discovery of digoxin-like factor in blood which could bind to a specific receptor on Na+, K(+)-ATPase subunit, showing also the affinity for cardiac glucosides. Digoxin-like factor was detected in blood of healthy people who did not receive any drug treatments. It has been estimated to be present in 15% of the population but in some diseases this value is much higher, e.g. digoxin-like factor was detected in 90% of patients with IDDM, and it can be used as a risk factor of the occurrence of vascular complications. In cases with NIDDM, the digoxin-like factor was detected in patients with insulin-resistance. The presence of digoxin-like factor was ascertained in patients with heart failure who did not take digitalis preparations. Endogenous digoxin-like factor can contribute to the detection of falsely increased digoxin blood concentrations during the monitoring of drug level in the course of the therapy. In our studies we ascertained the presence of the quinidine-, cyclosporin-, theophylline- and phenytoin-like substances in the blood of the healthy people who did not receive any drugs. It seems that these endogenous substances resembling drugs are synthesized in human organism when they are needed for maintaining the physiological equilibrium. We can suggest that stimulation of the production of drug-like factors in the organism can be used in the future in the therapy of some diseases.
Pol J Pharmacol
PMID:Endogenous drug-like factors. 1038 21

Disturbances of Na(+)-K(+)-ATPase activity in patients with respiratory insufficiency may cause the hypertonia of non-striated muscles, which leads to increased peripheral resistance or bronchoconstriction, and also may inhibit the uptake of catecholamines and therefore may intensify their action on the respiratory and circulatory systems. All this is very harmful in respiratory insufficiency. The aim of the study was the examination if there are any changes in sodium efflux through lymphocytic cell membrane in patients with chronic respiratory insufficiency and if retraction of insufficiency can influence the activity of Na(+)-K(+)-ATPase. The study was performed in 40 patients with chronic respiratory insufficiency, of these 11 were women aged from 58 to 72 years and 29 were men aged from 62 to 77 years. Control group consisted of 31 healthy persons, of these 9 were women aged from 37 to 55 and 22 years were men aged from 21 to 60 years. In the study we included patients with exacerbation of chronic obstructive pulmonary disease (COPD). Blood samples were obtained during the exacerbation of COPD and after partial improvement. We determined arterial blood gases and rates of total, ouabain-sensitive and furosemide-sensitive sodium efflux through lymphocytic cell membrane in venous blood. The rates of sodium efflux were estimated with the method described by Haegerty et al. In the study we showed that in patients with exacerbation of COPD rates of total and ouabain-sensitive sodium efflux through lymphocytic cell membrane were decreased, but after improvement of the disease these rates normalized. In patients with exacerbation of COPD rates of furosemide-sensitive sodium efflux were normal. Disturbances of activity of Na(+)-K(+)-ATPase in patients with exacerbation of chronic pulmonary insufficiency are due to hypoxia.
Pol Arch Med Wewn 1998 Dec
PMID:[Sodium efflux through lymphocytic cell membranes in patients with chronic respiratory insufficiency]. 1040 66


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