Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.7.48 (transcriptase)
9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A key protein in the production and in the maintenance of the endocochlear potential is the Na,K-ATPase. Previously, we have shown that FXYD6 is a modulator of the Na,K-ATPase expressed in the inner ear (Delprat et al. [2007] J Biol Chem 282:7450-7456). To investigate the potential role of FXYD6 in inner ear function, we studied the developmental expression of FXYD6. Reverse transcriptase-polymerase chain reaction analysis demonstrates that FXYD6 is present as two splice variants. Both variants coimmunoprecipitate with Na,K-ATPase after expression in Xenopus oocytes. Immunohistochemistry of the cochlea (from birth to postnatal day 30) shows that FXYD6 is expressed in several epithelial cells important for endolymph homeostasis. Marked similarities were found in the developmental expression patterns of FXYD6 and Na,K-ATPase, suggesting functional cooperation between the two proteins in the generation and maintenance of the endocochlear potential and ion composition of the endolymph.
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PMID:Dynamic expression of FXYD6 in the inner ear suggests a role of the protein in endolymph homeostasis and neuronal activity. 1767 40

The establishment of a symbiotic interaction between plant roots and arbuscular mycorrhizal (AM) fungi requires both partners to undergo significant morphological and physiological modifications which eventually lead to reciprocal beneficial effects. Extensive changes in gene expression profiles recently have been described in transcriptomic studies that have analyzed the whole mycorrhizal root. However, because root colonization by AM fungi involves different cell types, a cell-specific gene expression pattern is likely to occur. We have applied the laser microdissection (LMD) technology to investigate expression profiles of both plant and fungal genes in Lycopersicon esculentum roots colonized by Glomus mosseae. A protocol to harvest arbuscule-containing cells from paraffin sections of mycorrhizal roots has been developed using a Leica AS LMD system. RNA of satisfactory quantity and quality has been extracted for molecular analysis. Transcripts for plant phosphate transporters (LePTs), selected as molecular markers for a functional symbiosis, have been detected by reverse-transcriptase polymerase chain reaction assays and associated to distinct cell types, leading to novel insights into the distribution of LePT mRNAs. In fact, the transcripts of the five phosphate transporters (PTs) have been detected contemporaneously in the same arbusculated cell population, unlike from the neighboring noncolonized cells. In addition, fungal H(+)ATPase (GmHA5) and phosphate transporter (GmosPT) mRNAs were found exclusively in arbusculated cells. The discovery that five plant and one fungal PT genes are consistently expressed inside the arbusculated cells provides a new scenario for plant-fungus nutrient exchanges.
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PMID:Laser microdissection reveals that transcripts for five plant and one fungal phosphate transporter genes are contemporaneously present in arbusculated cells. 1784 8

The brine shrimp Artemia thrives at extreme conditions of up to 300 g/l salt in hypersaline lakes, but the molecular aspects of this salt adaptation are not clarified. To examine the influence of salt on the expression of two isoforms of Na,K-ATPase, adult Artemia franciscana were cultured for 39 days with the microalga Dunaliella salina as fodder at increasing salt from 30 to 280 g/l. Quantitative reverse-transcriptase polymerase chain reaction showed that the abundance of mRNA of the lysine-substituted alpha(2)(KK)-subunit was very low at 30 g/l salt but rose steeply in the range of 70-200 g/l to a level at 200-280 g/l salt, similar to the abundance of the mRNA of the alpha(1)(NN)-subunit, which was insignificantly affected by increasing salt. Site-directed mutagenesis showed that Asn324Lys and Asn776Lys in the alpha(1)-subunit of pig kidney Na,K-ATPase reduced the stoichiometry of (204)Tl binding from 2 to about 1 Tl(+)(K(+)) per alpha-subunit and Na(+)-dependent phosphorylation from ATP to 25-30%. In structure models, the epsilon-amino group of Lys776 is located at cation site 1 in the E(1)P form and near cation site 2 in the E(2) conformation, while the side chain of Lys324 points away from the cation sites. Salt-induced expression of the alpha(2)(KK)-subunit Na,K-ATPase in A. franciscana may reduce the Na(+)/ATP ratio and enable the Na,K pump to extrude Na(+) against steeper gradients and, thus, contribute to salt adaptation.
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PMID:Regulation and function of lysine-substituted Na,K pumps in salt adaptation of Artemia franciscana. 1807 67

cDNAs specifically expressed at the basidiome stage were isolated by using PCR-selected cDNA subtraction in order to study gene regulation during porous-hymenium basidiomatal formation in Antrodia cinnamomea. blastx results suggested that most of the expressed sequence tags (52.4-69.5%) had no significant protein homology to genes from other published living things. cDNAs particularly expressed at different growing conditions were identified using cDNA microarray analysis. Reverse transcriptase PCR analyses confirmed that the clone putative to P-type ATPase, various cytochrome P450s and some unknown genes were abundant at natural basidiomes while endoglucanase was abundant at the tissue from artificial medium.
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PMID:Isolation and analysis of genes specifically expressed during basidiomatal development in Antrodia cinnamomea by subtractive PCR and cDNA microarray. 1821 21

Aged individuals have impaired diastolic relaxation-lusitropic function. Dobutamine, a selective B1-adrenergic agonist, is used to augment systolic cardiac function at the termination of cardiopulmonary bypass (CPB). However, our question is whether dobutamine will also enhance the lusitropic function in the aged individual. The myocyte mechanism for the rate of ventricular relaxation is dependent on the velocity of calcium removal from the myocyte contractile elements by sarcoplasmic reticulum (SR) Ca(2+)-ATPase (SERCA2a), which is regulated by an inhibitory protein, phospholamban (PLB). Ventricular tissues harvested from young (4 month) and aged (20 months) mice were analyzed to compare the protein levels of SERCA2a and PLB with immunoblot and gene expression for PLB with reverse-transcriptase-polymerase chain reaction. The molecular analyses were compared with in vivo left ventricular function in the young and old mice before and during an intravenous infusion of dobutamine (5 microg/kg/min). The SERCA2a levels were not different between the groups; however, there was a 2-fold increase in PLB in the aged group compared with the young group (p < .05). The gene expression for PLB was increased by 5-fold in the aged group compared with the young group (p < .01). There were significant differences between the young and aged groups related to the lusitropic parameters, tau and dP/dt(min), and dobutamine infusion increased these parameters in the aged group to that of the young group. This report supports the concept that altered PLB levels correspond with the respective lusitropic function and that dobutamine administration in the aged group increased lusitropic function that was comparable with the young group. Because the patient population requiring CPB is aging, these data suggest that the use of dobutamine at the terminal phase of CPB is warranted to increase systolic and diastolic function.
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PMID:Lusitropic effects of dobutamine in young and aged mice in vivo. 1838 60

Influenza is a disease for deeply affecting millions of people every year. Recently, there has been considerable concern regarding the highly pathogenic H5N1 avian influenza virus, and its human pandemic potential. With developments in viral biology, there are more novel antiviral strategies targeting these viruses. In this review, we will discuss several proven and potential anti-influenza targets, including viral factors (such as hemagglutinin (HA), M2 ion channel protein, RNA-dependent RNA polymerase (RdRp), nucleoprotein (NP), non-structural protein (NS) and neuraminidase (NA)) and host factors (such as v-ATPase, protease, inosine monophosphate dehydrogenase (IMPDH) and intracellular signalling cascades), and their relevant inhibitors.
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PMID:Potential targets and their relevant inhibitors in anti-influenza fields. 1974 44

There are two protein primers involved in picornavirus RNA replication, VPg, the viral protein of the genome, and VPgpUpU(OH). A cis-acting replication element (CRE) within the open reading frame of poliovirus (PV) RNA allows the viral RNA-dependent RNA polymerase 3D(Pol) to catalyze the conversion of VPg into VPgpUpU(OH). In this study, we used preinitiation RNA replication complexes (PIRCs) to determine when CRE-dependent VPg uridylylation occurs relative to the sequential synthesis of negative- and positive-strand RNA. Guanidine HCl (2 mM), a reversible inhibitor of PV 2C(ATPase), prevented CRE-dependent VPgpUpU(OH) synthesis and the initiation of negative-strand RNA synthesis. VPgpUpU(OH) and nascent negative-strand RNA molecules were synthesized coincident in time following the removal of guanidine, consistent with PV RNA functioning simultaneously as a template for CRE-dependent VPgpUpU(OH) synthesis and negative-strand RNA synthesis. The amounts of [(32)P]UMP incorporated into VPgpUpU(OH) and negative-strand RNA products indicated that 100 to 400 VPgpUpU(OH) molecules were made coincident in time with each negative-strand RNA. 3'-dCTP inhibited the elongation of nascent negative-strand RNAs without affecting CRE-dependent VPg uridylylation. A 3' nontranslated region mutation which inhibited negative-strand RNA synthesis did not inhibit CRE-dependent VPg uridylylation. Together, the data implicate 2C(ATPase) in the mechanisms whereby PV RNA functions as a template for reiterative CRE-dependent VPg uridylylation before and during negative-strand RNA synthesis.
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PMID:Conversion of VPg into VPgpUpUOH before and during poliovirus negative-strand RNA synthesis. 1981 61

Hepatitis E virus (HEV) is a causative agent of acute hepatitis, and it is the sole member of the genus Hepevirus in the family Hepeviridae. The open reading frame 1 (ORF1) protein of HEV encodes nonstructural polyprotein with putative domains for methyltransferase, cysteine protease, helicase and RNA-dependent RNA polymerase. It is not yet known whether ORF1 functions as a single protein with multiple domains or is processed to form separate functional units. On the basis of amino acid conserved motifs, HEV helicase has been grouped into helicase superfamily 1 (SF-1). In order to examine the RNA helicase activity of the NTPase/helicase domain of HEV, the region (amino acids 960 to 1204) was cloned and expressed as histidine-tagged protein in Escherichia coli (HEV Hel) and purified. HEV Hel exhibited NTPase and RNA unwinding activities. Enzyme hydrolyzed all rNTPs efficiently, dATP and dCTP with moderate efficiency, while it showed less hydrolysis of dGTP and dTTP. Enzyme showed unwinding of only RNA duplexes with 5' overhangs showing 5'-to-3' polarity. We also expressed and purified two HEV Hel mutants. Helicase mutant I, with substitution in the nucleotide-binding motif I (GKS to GAS), showed 30% ATPase activity. Helicase mutant II, with substitutions in the Mg(2+) binding motif II (DEAP to AAAP), showed 50% ATPase activity. Both mutants completely lost ability to unwind RNA duplexes with 5' overhangs. These findings represent the first report demonstrating NTPase/RNA helicase activity of the helicase domain of HEV ORF1.
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PMID:NTPase and 5' to 3' RNA duplex-unwinding activities of the hepatitis E virus helicase domain. 2007 63

Picornaviridae is one of the largest viral families and is composed of 14 genera, six of which include human pathogens. The best known picornaviruses are enteroviruses (including polio, PV, and rhinoviruses), foot-and-mouth disease virus (FMDV), and hepatitis A virus (HAV). Although infections often are mild, certain strains may cause pandemic outbreaks accompanied with meningitis and/or paralysis. Vaccines are available for PV, HAV and FMDV. When the oral vaccines are given to immunocompromised individuals, they may be chronically infected, and remain secretors of vaccine-derived variants of virus for years. There is no effective prophylaxis available for these or other picornaviruses. So far, only the 3C protease from viruses in three genera has been fully characterized as an anti-viral target, whereas the mode of action of compounds targeting other non-structural proteins have remained largely unaddressed. Within the EU-supported FP6 project-VIZIER (Comparative Structural Genomics of Viral Enzymes Involved in Replication), the non-structural proteins were studied to identify conserved binding sites for broadly reactive anti-virals. The putative 2C helicase from echovirus-30 was shown to form ring-shaped hexamers typical for DNA-encoded SF3 helicases, and to possess ATPase activity. Hexamer formation of 2C from enterovirus 76 was in vitro shown to be dependent on the 44 N-terminal residues. Crystal structures of three enterovirus 3C proteases were solved and shown to be similar to those of other picornaviruses. A new binding site of VPg to the bottom of the thumb domain of CV-B3 3D polymerase was identified as a potential target. Broad anti-enterovirus compounds against 2C and 3A proteins were also identified, including thiazolobenzimidazoles (active against 2C) and TTP-8307 (targeting 3A). There is a need for more potent inhibitors against PV and other picornaviruses, which are potential silent reservoirs for re-emerging PV-like disease.
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PMID:Picornavirus non-structural proteins as targets for new anti-virals with broad activity. 2123 2

FXYD proteins, small single-transmembrane proteins, have been proposed to be auxiliary regulatory subunits of Na(+)-K(+)-ATPase and have recently been implied in ion osmoregulation of teleost fish. In freshwater (FW) fish, numerous ions are actively taken up through mitochondrion-rich cells (MRCs) of the gill and skin epithelia, using the Na(+) electrochemical gradient generated by Na(+)-K(+)-ATPase. In the present study, to understand the molecular mechanism for the regulation of Na(+)-K(+)-ATPase in MRCs of FW fish, we sought to identify FXYD proteins expressed in MRCs of zebrafish. Reverse-transcriptase PCR studies of adult zebrafish tissues revealed that, out of eight fxyd genes found in zebrafish database, only zebrafish fxyd11 (zfxyd11) mRNA exhibited a gill-specific expression. Double immunofluorescence staining showed that zFxyd11 is abundantly expressed in MRCs rich in Na(+)-K(+)-ATPase (NaK-MRCs) but not in those rich in vacuolar-type H(+)-transporting ATPase. An in situ proximity ligation assay demonstrated its close association with Na(+)-K(+)-ATPase in NaK-MRCs. The zfxyd11 mRNA expression was detectable at 1 day postfertilization, and its expression levels in the whole larvae and adult gills were regulated in response to changes in environmental ionic concentrations. Furthermore, knockdown of zFxyd11 resulted in a significant increase in the number of Na(+)-K(+)-ATPase-positive cells in the larval skin. These results suggest that zFxyd11 may regulate the transport ability of NaK-MRCs by modulating Na(+)-K(+)-ATPase activity, and may be involved in the regulation of body fluid and electrolyte homeostasis.
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PMID:Identification of zebrafish Fxyd11a protein that is highly expressed in ion-transporting epithelium of the gill and skin and its possible role in ion homeostasis. 2142 71


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