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)

In cultured alveolar epithelial cells, hypoxia induces a downregulation of the two main Na proteins, the epithelial Na channel (ENaC) and the Na,K-ATPase. However, the in vivo effects of hypoxia on alveolar epithelial transport have not been well studied. Therefore, the objectives of this study were to investigate in an in vivo rat model if hypoxia induces a reduction in vectorial Na and fluid transport across the alveolar epithelium in vivo, and if a change in net fluid transport is associated with modification in the expression and/or activity of Na transport proteins. Rats were exposed to 8% O(2) from 3 to 24 h. Hypoxia induced a progressive decrease in alveolar liquid clearance (ALC) reaching 50% at 24 h, an effect that was related primarily to a decrease in amiloride-sensitive transepithelial Na transport. On RNase protection assay of alveolar type II (ATII) cells isolated immediately after hypoxic exposure, steady state levels of mRNA were increased for alpha-rENaC and beta(1)-Na, K-ATPase, whereas the levels of gamma-rENaC and alpha(1)-Na,K-ATPase were unchanged. On Western blots of ATII cell membranes, alpha-ENaC subunit protein slightly increased, whereas the amount of alpha(1)- and beta(1)-Na,K-ATPase protein were unchanged with hypoxia. Thus, the decrease in transepithelial Na transport was not explained by a parallel change in gene expression or the quantity of transport proteins. Interestingly, hypoxia-induced decrease in ALC was completely reversed by intra-alveolar administration of the beta(2) agonist, terbutaline (10(-4) M). These results suggest that hypoxia-induced decrease in Na transport is not simply related to a downregulation of Na transport proteins but rather to a decrease in Na protein activity by either internalization of the proteins and/or direct alteration of the protein in the membrane. The dramatic increase of ALC with beta(2)-agonist therapy indicates that the decrease of transepithelial Na and fluid transport during hypoxia is rapidly reversible, a finding of major clinical significance.
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PMID:Hypoxia reduces alveolar epithelial sodium and fluid transport in rats: reversal by beta-adrenergic agonist treatment. 1171 96

We have found using differential display of mRNA that the growth factor heregulin beta 1 (HRG), a combinatorial ligand for human epidermal growth factor receptors (HERs), induced expression of G3BP, the Ras GTPase-activating protein SH3 domain-binding protein, in breast cancer cells. G3BP is a downstream effector protein of Ras signaling with ATP-dependent RNase and helicase activities, which may link Ras signaling with RNA turnover and cell cycle progression. In human breast cancer cells, HRG induced G3BP mRNA and protein expression. Up-regulation of G3BP was found in MCF7 breast cancer cells overexpressing HER2. G3BP was also overexpressed in human breast tumors in parallel with HER2 overexpression and in an estrogen-independent manner, suggesting a role for G3BP in cancer progression. In addition, HRG stimulation of breast cancer cells promoted phosphorylation of G3BP and increased the association of G3BP with GTPase-activating protein, both of which are essential for G3BP activity. G3BP ATPase activity was also significantly increased by HRG treatment. Furthermore, HRG treatment resulted in G3BP translocation to the nucleus and colocalization with acetylated histone H3, a hallmark of active transcription sites. G3BP induction, phosphorylation, ATPase activity, and relocalization after HRG treatment could all be blocked by pretreatment with the anti-receptor HER2 monoclonal antibody Herceptin (trastuzumab), which may suggest additional applications for this therapeutic antibody. These findings demonstrate for the first time the receptor-dependent regulation of G3BP, a downstream effector of Ras signaling, by HRG, a growth factor with diverse functions in breast cancer cells.
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PMID:Heregulin induces expression, ATPase activity, and nuclear localization of G3BP, a Ras signaling component, in human breast tumors. 1188 85

The accurate classification of skeletal muscle fiber types according to myosin heavy chain (MyHC) polymorphism remains a difficult task in the pig. Combined myofibrillar ATPase and metabolic enzyme histochemistry, in situ hybridization, and immunocytochemistry were performed on serial transverse sections of pig longissimus (L) and rhomboideus (R) muscles at 100 kg body weight to give a new insight into muscle fiber typing in the pig. Several monoclonal antibodies (MAbs) either specific for a single MyHC (I, IIa, or IIb) or of multiple MyHCs (IIa + IIx or I + IIx + IIb) were used. No monospecific IIx antibody was available for the pig. All three adult Type II isoforms were expressed in the white L muscle, whereas no IIb was observed in the red R muscle, which was confirmed using RNase protection analysis. In most fibers, the distribution of the transcripts closely matched that of the corresponding proteins. When observed, co-expression of MyHCs mostly occured for IIx and IIb in L muscle, and was more common at the protein (11.5%) than at the mRNA (2.2%) level. A minor proportion of myofibers showed a mismatch between MyHC mRNA and protein. According to the type grouping distribution of myofibers encountered in pig muscle, MyHC isoform expression followed the rank order of I-->IIa-->IIx-->IIb from the center to the periphery of the islets, concomitantly with a decrease in oxidative metabolism and an increase in fiber size. The developmental origin and functional significance of the type grouping distribution are discussed.
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PMID:New insights into muscle fiber types in the pig. 1196 83

A thermogenic organ is found beneath the brain of billfishes (Istiophoridae), swordfish (Xiphiidae) and the butterfly mackerel (Scombridae). The heater organ has been shown to warm the brain and eyes up to 14 degrees C above ambient water temperature. Heater cells are derived from extraocular muscle fibers and express a modified muscle phenotype with an extensive transverse-tubule (T-tubule) network and sarcoplasmic reticulum (SR) enriched in Ca(2+)-ATPase (SERCA) pumps and ryanodine receptors (RyRs). Heater cells have a high mitochondria content but have lost most of the contractile myofilaments. Thermogenesis has been hypothesized to be associated with release and reuptake of Ca(2+). In this study, Ca(2+) fluxes in heater SR vesicles derived from blue marlin (Makaira nigricans) were measured using fura-2 fluorescence. Upon the addition of MgATP, heater SR vesicles rapidly sequestered Ca(2+). Uptake of Ca(2+) was thapsigargin sensitive, and maximum loading ranged between 0.8 micro mol Ca(2+) mg(-1) protein and 1.0 micro mol Ca(2+) mg(-1) protein. Upon the addition of 10 mmol l(-1) caffeine or 350 micro mol l(-1) ryanodine, heater SR vesicles released only a small fraction of the loaded Ca(2+). However, ryanodine could elicit a much larger Ca(2+) release event when the activity of the SERCA pumps was reduced. RNase protection assays revealed that heater tissue expresses an RyR isoform that is also expressed in fish slow-twitch skeletal muscle but is distinct from the RyR expressed in fish fast-twitch skeletal muscle. The heater and slow-twitch muscle RyR isoform has unique physiological properties. In the presence of adenine nucleotides, this RyR remains open even though cytoplasmic Ca(2+) is elevated, a condition that normally closes RyRs. The fast Ca(2+) sequestration by the heater SR, coupled with a physiologically unique RyR, is hypothesized to promote Ca(2+) cycling, ATP turnover and heat generation. A branch of the oculomotor nerve innervates heater organs, and, in this paper, we demonstrate that heater cells contain large 'endplate-like' clusters of acetylcholine receptors that appear to provide a mechanism for nervous control of thermogenesis.
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PMID:Characterization of ryanodine receptor and Ca2+-ATPase isoforms in the thermogenic heater organ of blue marlin (Makaira nigricans). 1254 35

Lactoferrin (LF) is a Fe3+-binding glycoprotein, first recognized in milk and then in other human epithelial secretions and barrier fluids. Many different functions have been attributed to LF, including protection from iron-induced lipid peroxidation, immunomodulation and cell growth regulation, DNA binding, and transcriptional activation. Its physiological role is still unclear, but it has been suggested to be responsible for primary defense against microbial and viral infection. We present evidence that different subfractions of purified human milk LF possess five different enzyme activities: DNase, RNase, ATPase, phosphatase, and malto-oligosaccharide hydrolysis. LF is the predominant source of these activities in human milk. Some of its catalytically active subfractions are cytotoxic and induce apoptosis. The discovery that LF possesses these activities may help to elucidate its many physiological functions, including its protective role against microbial and viral infection.
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PMID:Multiple enzymic activities of human milk lactoferrin. 1289 92

Mice lacking the mesenchymal winged helix transcription factor Foxl1 exhibit markedly abnormal small intestinal epithelia and postnatal growth retardation. We investigated whether defects in intestinal nutrient uptake and specific transport processes exist in mice homozygous for a Foxl1 null allele (Foxl1-/-). Foxl1-/- mice and controls on a defined genetic background were weighed regularly and killed at 2, 4, and 12 wk of age. Intestinal uptake studies, quantitative real-time PCR, RNase protection assays, and Western blot analyses were performed. Foxl1-/- mice have dysmorphic small intestinal epithelia and postnatal growth retardation. Foxl1-/- mice demonstrate decreased small intestinal uptake of D-glucose in all age groups studied. Intestinal uptake of D-fructose and two amino acids, L-proline and L-leucine, is not altered. Consistent with these findings, Foxl1-/- mice show decreased levels of the intestinal D-glucose transporter SGLT1. Expression of sucrase-isomaltase, lactase, GLUT2, and Na+-K+ ATPase are not changed. Foxl1-/- mice demonstrate markedly abnormal intestinal epithelia, postnatal growth retardation, and decreased intestinal uptake of D-glucose. The specific effect of Foxl1 on intestinal d-glucose uptake is due to decreased production of SGLT1 protein in the small intestine. Thus we identified, for the first time, a link between a mesenchymal factor, Foxl1, and the regulation of a specific epithelial transport process.
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PMID:Foxl1 null mice have abnormal intestinal epithelia, postnatal growth retardation, and defective intestinal glucose uptake. 1515 78

The activity of glutamate dehydrogenase (GDH), an important enzyme in carbon and nitrogen metabolism, is routinely assayed by photometry. The RNA synthetic activity of the enzyme provides new technologies for assaying its activity. The enzyme was made to synthesize RNAs in the absence of DNA and total RNA but with different mixes of the four nucleoside triphosphates (NTPs) in order to investigate the RNA characteristics. RNase VI (hydrolyzes base-paired residues) digested the poly (U,A) RNA completely because the U and A residues were evenly distributed to produce many base-paired regions. Therefore, the synthesis of RNA by GDH was by random addition of NTPs. The RNA synthetic activity of the enzyme was at least 50-fold more active in the deamination than in the amination direction, thus providing a robust technology for assay of the enzyme's activity. cDNAs prepared from the RNAs were subjected to restriction fragment differential display polymerase chain reaction analyses. Sequencing of the cDNA fragments showed that some of the RNA synthesized by GDH shared sequence homology with total RNA. Database searches showed that the RNA fragments shared sequence homologies with the G proteins, adenosine triphosphatase, calmodulin, phosphoenol pyruvate (PEP) carboxylase, and PEP carboxykinase, thus explaining the molecular mode of their functions in signal transduction.
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PMID:RNA synthetic activity of glutamate dehydrogenase: determination of enzyme purity, RNA characteristics, and deamination/amination ratio. 1559 15

The ABC ATPase RNase-L inhibitor (RLI) emerges as a key enzyme in ribosome biogenesis, formation of translation preinitiation complexes, and assembly of HIV capsids. To help reveal the structural mechanism of RLI, we determined the Mg2+-ADP bound crystal structure of the twin cassette ATPase of P. furiosus RLI at 1.9 A resolution and analyzed functional motifs in yeast in vivo. RLI shows similarities but also differences to known ABC enzyme structures. Twin nucleotide binding domains (NBD1 and NBD2) are arranged to form two composite active sites in their interface cleft, indicating they undergo the ATP-driven clamp-like motion of the NBDs of ABC transporters. An unusual "hinge" domain along the NBD1:NBD2 interface provides a frame for association and possibly ATP-driven conformational changes of the NBDs. Our results establish a first structural basis for ABC domain heterodimers and suggest that RLI may act as mechanochemical enzyme in ribosome and HIV capsid biogenesis.
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PMID:X-ray structure of RLI, an essential twin cassette ABC ATPase involved in ribosome biogenesis and HIV capsid assembly. 1583 86

During pregnancy and immediately after delivery (i.e. at the beginning of lactation), the female organism is frequently characterized by an immune status similar to that of patients with autoimmune diseases. In addition, lactation is associated with an appearance of catalytically active antibodies or abzymes (Abzs) with DNAse, RNase, ATPase, amylolitic, protein kinase and lipid kinase activities in breast milk. However, until now there were no examples of human milk Abzs with a proteolytic activity. We present the first evidence that electrophoretically and immunologically homogeneous human milk sIgAs possess a beta-casein-hydrolyzing activity different from known proteases. Abzs specifically hydrolyze both human and bovine beta-caseins but not many other proteins tested. Using different methods including in situ analysis of proteolytic activity in a gel after SDS-PAGE it was shown that the observed proteolytic activity is an intrinsic property of human milk polyclonal sIgAs. Specific inhibitors of acidic and thiol proteases demonstrated a weak effect on proteolytic activity of Abzs, while a specific inhibitor of serine proteases (AEBSF) significantly inhibited the proteolytic activity of the abzymes. The K(M) value for human casein as a substrate was estimated (7.3 microM). Our findings suggest that the immune system of clinically healthy mothers can generate IgAs with a beta-casein-specific serine protease-like activity.
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PMID:Casein-hydrolyzing activity of sIgA antibodies from human milk. 1595 46

RecQ DNA helicases are multidomain enzymes that play pivotal roles in genome maintenance pathways. While the ATPase and helicase activities of these enzymes can be attributed to the conserved catalytic core domain, the role of the Helicase-and-RNase-D-C-terminal (HRDC) domain in RecQ function has yet to be elucidated. Here, we report the crystal structure of the E. coli RecQ HRDC domain, revealing a globular fold that resembles known DNA binding domains. We show that this domain preferentially binds single-stranded DNA and identify its DNA binding surface. HRDC domain mutations in full-length RecQ lead to surprising differences in its structure-specific DNA binding properties. These data support a model in which naturally occurring variations in DNA binding residues among diverse RecQ homologs serve to target these enzymes to distinct substrates and provide insight into a mechanism whereby RecQ enzymes have evolved distinct functions in organisms that encode multiple recQ genes.
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PMID:Conferring substrate specificity to DNA helicases: role of the RecQ HRDC domain. 1608 89


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