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)

ATPase activity of crythroyte membranes was determined in 25 cases of Down's syndrome verified by cytological and psychological examinations. The age range of the patients was 8-25 years; 16 males and 9 females. Thirty health male volunteers were selected as the control group. There was a marked reduction of total ATPase, Na+, K+-ATPase, Mg++ATPase activities and rate of ouabain inhibition in the patients with Down's syndrome. The authors suggest that there might exist transport defects in the red cell membranes in such patients.
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PMID:ATPase activity of erythrocyte membrane in patients with trisomy 21 (Down's syndrome). 609 54

Disturbance of central serotoninergic system has been suggested in Down's syndrome (DS). In this syndrome the 5-HT concentration in blood platelets is below normal, but the mechanism behind this has been controversial. Recently, evidence has accumulated indicating a decreased active transport of 5-HT possibly due to lowered activity of Mg++-dependent Na+-K+-stimulated adenosine triphosphatase. In the present study the kinetic analysis of 5-HT uptake by blood platelets from DS patients revealed a decreased Vmax, suggesting decreased transport function but an unchanged affinity to the uptake receptors, as indicated by normal Km values. The controls were mentally retarded patients from the same institute. The uptake continued in a linear fashion up to 20 min., suggesting an unchanged storage of 5-HT. Also the effect of zinc on the 5-HT uptake was studied; plasma zinc levels have been noted to be lowered in DS infants. In vitro zinc caused a dose-dependent inhibition of uptake at 10(-5) and 10(-4) M. In vivo, after 2 weeks treatment 135 mg/day orally no significant effect was noted.
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PMID:Nature of lowered 5-hydroxytryptamine uptake by blood platelets of patients with Down's syndrome. 645 3

Exon trapping was used to clone portions of potential genes from human chromosome 21. One trapped sequence showed striking homology with the bovine and rat ATP synthase OSCP (oligomycin sensitivity conferring protein) subunit. We subsequently cloned the full-length human ATP synthase OSCP cDNA (GDB/HGMW approved name ATP50) from infant brain and muscle libraries and determined its nucleotide and deduced amino acid sequence (EMBL/GenBank Accession No. X83218). The encoded polypeptide contains 213 amino acids, with more than 80% identity to bovine and murine ATPase OSCP subunits and over 35% identity to Saccharomyces cerevisiae and sweet potato sequences. The human ATP5O gene is located at 21q22.1-q22.2, just proximal to D21S17, in YACs 860G11 and 838C7 of the Chumakov et al. (Nature 359:380, 1992) YAC contig. The gene is expressed in all human tissues examined, most strongly in muscle and heart. This ATP5O subunit is a key structural component of the stalk of the mitochondrial respiratory chain F1F0-ATP synthase and as such may contribute in a gene dosage-dependent manner to the phenotype of Down syndrome (trisomy 21).
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PMID:Cloning of the cDNA for the human ATP synthase OSCP subunit (ATP5O) by exon trapping and mapping to chromosome 21q22.1-q22.2. 749 82

At 10-14 weeks of gestation about 80% of fetuses with chromosomal defects have abnormal accumulation of subcutaneous fluid in the nuchal region that is visualized by ultrasonography as nuchal translucency. A possible cause for this translucency is cardiac dysfunction due to the associated defects in the heart and great arteries. The aim of this study was to investigate whether in cardiac tissue from trisomic fetuses, compared to normals, there is an alteration in the steady state levels of expression of the genes encoding sarcoplasmic reticulum calcium ATPase (calcium ATPase), which is known to be downregulated in postnatal heart failure. After termination of pregnancy at 10-18 weeks of gestation, mRNA was extracted from cardiac tissue in 11 trisomy 21 and 4 trisomy 18 fetuses. Densitometric analysis of the Northern and slot blots was used to determine the steady state levels of expression of calcium ATPase and the values from the trisomic fetuses were compared to those of 30 normal controls at 10-18 weeks. Calcium ATPase gene expression did not change significantly with gestation at 10-18 weeks. In trisomic fetuses there was no significant decrease in calcium ATPase expression and expression levels of calcium ATPase were not related to increased nuchal translucency. However, the levels expressed in fetuses are already very low and cardiac dysfunction as a potential etiological factor cannot be excluded.
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PMID:Cardiac expression of sarcoplasmic reticulum calcium ATPase in fetuses with trisomy 21 and trisomy 18 presenting with nuchal translucency. 943 Feb 6

Ubiquinol:cytochrome c oxidoreductase (complex III) and ATP synthase (complex V) are important enzymes in the mitochondrial electron transport chain. Defects in mitochondrial respiratory enzymes have been reported for several neurodegenerative diseases. In this study, we applied the proteomic approach to investigate protein levels of complex III core protein and complex V beta chain in brain regions of Alzheimer's disease (AD) and Down syndrome (DS) patients. Complex III core protein 1 was significantly reduced in the temporal cortex of AD patients. Complex V beta chain was significantly reduced in the frontal cortex of DS patients. We conclude that decreased mitochondrial respiratory enzymes could contribute to the impairment of energy metabolism observed in DS. These decreases could also cause the generation of reactive oxygen species and neuronal cell death (apoptosis) in DS as well as AD.
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PMID:Decreased levels of complex III core protein 1 and complex V beta chain in brains from patients with Alzheimer's disease and Down syndrome. 1113 Jan 85

The isoprenoid pathway related cascade was assessed in trisomy 21 and Huntington's disease. Membrane Na+-K+ ATPase activity, serum magnesium and ubiquinone were decreased while HMG CoA reductase activity, serum digoxin and dolichol levels were increased in both the disorders. There were increased levels of tryptophan catabolites (nicotine, strychnine, quinolinic acid and serotonin) and decreased levels of tyrosine catabolites (dopamine, noradrenaline and morphine) in both trisomy 21 and Huntington's disease. There was an increase in dolichol levels, carbohydrate residues of glycoproteins, glycolipids, total/individual GAG fractions and lysosomal enzymes in both disorders. Reduced levels of ubiquinone, reduced glutathione and free radical scavenging enzymes as well as increased lipid peroxidation products and nitric oxide were noticed in both the disorders. The role of hypothalamic digoxin and a disordered isoprenoid pathway in the pathogenesis of trisomy 21 and Huntington's disease is discussed.
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PMID:Endogenous sodium-potassium ATPase inhibition related biochemical cascade in trisomy 21 and Huntington's disease: neural regulation of genomic function. 1213 82

The study assessed the isoprenoid pathway, digoxin synthesis, and neurotransmitter patterns in individuals of differing hemispheric dominance, neurogenetic disorders, and neoplasms. The HMG CoA reductase activity, serum digoxin, magnesium, tryptophan catabolites, tyrosine catabolites, and RBC membrane Na+-K+ ATPase activity were measured in individuals of differing hemispheric dominance. The digoxin status, membrane Na+-K+ ATPase activity, and serum magnesium were assessed in Huntington's disease, trisomy 21, glioblastoma multiforme, and non-Hodgkin's lymphoma (high grade lymphoma). The results showed that right hemispheric, chemically dominant individuals had elevated digoxin synthesis, increased tryptophan catabolites, and reduced tyrosine catabolites, and membrane Na+-K+ ATPase with hypomagnesemia. Left hemispheric, chemically dominant individuals had the opposite patterns. In neurogenetic disorders and neo plasms also hyperdigoxinemia induced membrane Na+-K+ ATPase inhibition, and hypomagnesemia similar to right hemispheric chemical dominance could be demonstrated. The role of hemispheric chemical dominance and hypothalamic digoxin secretion play a key role in the regulation of cell differentiation/proliferation and genomic function. Ninety-five percent of the patients with neurogenetic disorders and neoplasms were right-handed/left hemispheric dominant by dichotic listening test. However, all of them had biochemical patterns similar to right hemispheric chemical dominance. Hemispheric chemical dominance has no correlation to cerebral dominance detected by handness/dichotic listening test.
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PMID:Cerebral chemical dominance and neural regulation of cell division, cell proliferation, neoplastic transformation, and genomic function. 1274 28

The isoprenoid pathway related cascade was assessed in trisomy 21. Membrane Na+, K(+)-ATPase activity, serum magnesium, and ubiquinone were decreased while hydroxy methyl glutaryl CoA (HMG) coenzyme A (CoA) reductase activity, serum digoxin, and dolichol levels were increased in trisomy 21. There were increased levels of tryptophan catabolites--nicotine, strychnine, quinolinic acid, and serotonin--and decreased levels of tyrosine catabolites--dopamine, noradrenaline, and morphine in trisomy 21. There was an increase in dolichol levels, carbohydrate residues of glycoproteins, glycolipids, total/individual glycosaminoglycan (GAG) fractions, and lysosomal enzymes in trisomy 21. Reduced levels of ubiquinone, reduced glutathione, and free radical scavenging enzymes as well as increased lipid peroxidation products and nitric oxide were noticed in trisomy 21. Hypothalamic digoxin and a disordered isoprenoid pathway are important in the pathogenesis of trisomy 21.
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PMID:Hypothalamic digoxin-mediated model for trisomy 21. 1469 93

The success of the Human Genome Project (HGP) enables prediction of proteins by computer programs from nucleic acid sequences and for which there is no experimental evidence. Clues for function of hypothetical proteins are provided by sequence similarity with proteins of known function in model organisms. The availability of this bulk of new data is of immediate importance to Down's syndrome (DS) research. DS is the most common human chromosomal abnormality caused by an extra copy of chromosome 21 and is characterized by somatic anomalies and mental retardation. In addition, overexpression of chromosome 21 genes is directly or indirectly responsible for mental retardation and other phenotypic abnormalities of DS. To allow insight into how trisomy 21 represents the phenotype of DS, we constructed a two-dimensional protein map and investigated expression of 8 hypothetical proteins in fetal DS (n = 7) and control (n = 7) brains (cortex). Two-dimensional electrophoresis (2-DE) with subsequent in-gel digestion of spots and matrix-assisted laser desorption/ionization (MALDI) spectroscopic identification followed by quantification of spots with specific software was applied. Quantitative analysis of hypothetical protein FLJ10849, hypothetical protein FLJ20113, and activator of hsp90 ATPase homologue 1 (AHA1) revealed levels comparable between DS and controls. By contrast, expression levels of hypothetical protein KIAA1185, hypothetical protein 55.2 kDa, hypothetical protein 58.8 kDa, actin-related protein 3beta (ARP3beta), and putative GTP-binding protein PTD004 were significantly decreased (P < 0.05) in fetal DS brain, and domain analysis suggests involvement in cytoskeleton, signaling, and chaperone system abnormalities.
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PMID:Derangement of hypothetical proteins in fetal Down's syndrome brain. 1517 87

Spf1p is a P-type ATPase that is mainly localized to the endoplasmic reticulum (ER) in Saccharomyces cerevisiae. The protein is involved in the maintenance of ion homeostasis in the ER. To investigate the intracellular role of Spf1p in more detail, we performed a genetic screen for mutations that lead to synthetic lethality in combination with a disruption of SPF1; the mutations identified have been termed lws (for lethal with spf1) mutations. Mutant alleles of five LWS genes (MDM39, RIC1, LAS21, TUP1 and BTS1) were recovered. The identification of these genes provides clues to the physiological relationships between Spf1p function and the secretory pathway. Among the five genes identified, MDM39 encodes a membrane protein that is similar to the protein CHD5/WRB, which is involved in the pathogenesis of Down syndrome-associated congenital heart disease in humans. We localized Mdm39p to the ER. The Deltamdm39 mutant exhibited defects in glycosylation, cell wall organization and the unfolded protein response. It also showed calcium-related phenotypes and synthetic lethal interactions with deletion mutations in other LWS genes. Our findings imply a homeostatic role for Mdm39p, which may be related to the regulation of calcium ion fluxes in the ER, and is indispensable for mutants that lack Spf1p.
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PMID:Cooperative function of the CHD5-like protein Mdm39p with a P-type ATPase Spf1p in the maintenance of ER homeostasis in Saccharomyces cerevisiae. 1590 63


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