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)

The phosphoprotein P of Borna disease virus (BDV) is an essential cofactor of the viral RNA-dependent RNA polymerase. It is preferentially phosphorylated at serine residues 26 and 28 by protein kinase C epsilon (PKCepsilon) and, to a lesser extent, at serine residues 70 and 86 by casein kinase II (CKII). To determine whether P phosphorylation is required for viral polymerase activity, we generated P mutants lacking either the PKCepsilon or the CKII phosphate acceptor sites by replacing the corresponding serine residues with alanine (A). Alternatively, these sites were replaced by aspartic acid (D) to mimic phosphorylation. Functional characterization of the various mutants in the BDV minireplicon assay revealed that D substitutions at the CKII sites inhibited the polymerase-supporting activity of P, while A substitutions maintained wild-type activity. Likewise, D substitutions at the PKC sites did not impair the cofactor function of BDV-P, whereas A substitutions at these sites led to increased activity. Interestingly, recombinant viruses could be rescued only when P mutants with modified PKCepsilon sites were used but not when both CKII sites were altered. PKCepsilon mutant viruses showed a reduced capacity to spread in cell culture, while viral RNA and protein expression levels in persistently infected cells were almost normal. Further mutational analyses revealed that substitutions at individual CKII sites were, with the exception of a substitution of A for S86, detrimental for viral rescue. These data demonstrate that, in contrast to other viral P proteins, the cofactor activity of BDV-P is negatively regulated by phosphorylation.
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PMID:Functional characterization of the major and minor phosphorylation sites of the P protein of Borna disease virus. 1737 20

A new porous, thermoresponsive, partially biodegradable, chemically crosslinked hydrogel system was developed, characterized, and tested as a cartilage tissue-engineering scaffold for in vitro chondrocyte culture over a 4-week period. The hydrogel system was composed of poly(N-isopropylacrylamide), poly(D,L-lactic acid), and dextran segments. Pores in the hydrogels were generated using a salt leaching technique. The hydrogels showed thermoresponsive properties, with a lower critical solution temperature at approximately 32 degrees C. They continuously swelled at physiological temperature in phosphate buffered saline (pH 7.4) for at least 1 month. Chondrocytes isolated from embryonic chick sterna were seeded into the hydrogel scaffolds at room temperature and cultured at 37 degrees C for 4 weeks. Real-time reverse-transcriptase polymerase chain reaction quantification was conducted every week to study messenger ribonucleic acid levels of 3 chondrocyte phenotypic markers: type II collagen, type X collagen, and Indian hedgehog. Results suggested that chondrocytes maintained their phenotype during the 4-week in vitro culture and could mimic in vivo development. Chondrocytes were non-enzymatically harvested from the hydrogel scaffold at the end of the fourth week by simply lowering the temperature from 37 degrees C to room temperature. The harvested chondrocytes kept a round morphology, confirming the maintenance of the chondrocyte phenotype in the hydrogel scaffolds.
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PMID:Porous thermoresponsive-co-biodegradable hydrogels as tissue-engineering scaffolds for 3-dimensional in vitro culture of chondrocytes. 1768 45

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 importance of fibroblast growth factor 23 (FGF-23) in the pathogenesis of phosphate wasting disorders has been established, but controversy remains about how parathyroid hormone (PTH), which also stimulates urinary phosphate excretion, regulates the circulating level of FGF-23. We found that the serum FGF-23 concentration was higher in PTH-cyclin D1 transgenic mice, a model of primary hyperparathyroidism, than in wild-type mice. The serum FGF-23 concentration was significantly and directly correlated with serum PTH and calcium, and inversely correlated with phosphate levels in 90- to 118-week-old mice (all P < 0.005). Quantitative real-time reverse-transcriptase PCR revealed abundant expression of fgf23 in bone, especially in calvaria. The fgf23 expression in calvaria was significantly higher in the transgenic mice compared to the wild-type mice, and correlated well with serum FGF-23 levels. There was a direct correlation between the expression of fgf23 and the expression of osteocalcin and ALP, suggesting that activation of osteoblasts is important in the regulation of FGF-23. Serum FGF-23 levels decreased in the transgenic mice after parathyroidectomy. In conclusion, PTH plays a major role in the regulation of serum FGF-23 level in primary hyperparathyroidism, likely via activation of osteoblasts in bone.
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PMID:Parathyroid hormone regulates fibroblast growth factor-23 in a mouse model of primary hyperparathyroidism. 1785 36

Extracellular ATP facilitates the release of dopamine via P2 receptor activation in parts of the mesolimbic system. To characterize P2X/Y receptor subtypes in the developing dopaminergic system, their expression in organotypic slice co-cultures including the ventral tegmental area/substantia nigra (VTA/SN) complex and the prefrontal cortex (PFC) was studied in comparison to the receptor expression in 3-5 day-old and adult rats. Reverse transcriptase-polymerase chain reaction (RT-PCR) with specific primers for the P2X(1,2,3,4,6,7) and P2Y(1) receptors in the tissue extracts of organotypic co-cultures revealed the presence of the P2X and P2Y receptor mRNAs investigated. Multiple immunofluorescence labeling of the P2X/Y receptor protein indicated differences in the regional expression in the organotypic co-cultures after 10 days of cultivation (VTA/SN, P2X(1,2,3,4,6,7), P2Y(1,6,12); PFC, P2X(1,3,4,6,7), P2Y(1,2,4,6,12)). At postnatal days 3-5, an immunofluorescence mostly comparable to that of adult rats was observed (VTA/SN and PFC: P2X(1,2,3,4,6,7), P2Y(1,2,4,6,12)). There was one important exception: the P2X(7) receptor immunocytochemistry was not found in adult tissue, suggesting a potential role of this receptor in the development. Only few P2 receptors (e.g. P2X(1), P2Y(1)) were expressed at fibers interconnecting the dopaminergic VTA/SN with the PFC in the organotypic co-cultures. The treatment of the cultures with the ATP analogues 2-methylthio-ATP and alpha,beta-methylene-ATP induced an increase in axonal outgrowth and fiber density, which could be inhibited by pre-treatment with the P2X/Y receptor antagonist pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid. The co-localization of the dopamine-(D1) receptor with the P2X(1) receptor in organotypic slice cultures was evident. In the PFC of the co-cultures, and that of young but not adult rats, a number of tyrosine hydroxylase (TH)-positive cells also possessed P2Y(1)-immunoreactivity (IR). Additionally, a strong P2Y(1)-IR was observed on astrocytes. The present results show a time-, region- and cell type-dependent in vitro and in vivo expression pattern of different P2 receptor subtypes in the dopaminergic system indicating the involvement of ATP and its receptors in neuronal development and growth.
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PMID:P2 receptor expression in the dopaminergic system of the rat brain during development. 1786 6

Mesoscale physical processes (for example eddies, frontal meanders and planetary waves) can play important roles in controlling ocean biogeochemistry. We examined spatial variations in upper ocean (0-100 m) nutrient inventories, N(2) fixing microorganism diversity and abundance, and rates of N(2) fixation in an anticyclonic eddy near Station ALOHA (22 degrees 45' N, 158 degrees 00' W) in the North Pacific Subtropical Gyre (NPSG). In July 2005, satellite-based sea surface altimetry and ocean color observation revealed an anticyclonic eddy with enhanced chlorophyll in the upper ocean in the vicinity of Station ALOHA. Within the eddy, near-surface ocean chlorophyll concentrations were approximately 5-fold greater than in the surrounding waters. Inventories of nitrate and phosphate in the eddy were similar to the concentrations historically observed at Station ALOHA, while silicic acid inventories were significantly depleted (one-way analysis of variance, P<0.01). Quantitative PCR determinations of nifH gene copies revealed relatively high abundances of several N(2) fixing cyanobacteria, including Trichodesmium spp., Crocosphaera watsonii and Richelia intracellularis. Reverse transcriptase PCR (RT-PCR) amplified nitrogenase (nifH) gene transcripts were cloned and sequenced to examine the diversity of active N(2) fixing microorganisms; these clone libraries were dominated by sequence-types 97%-99% identical to the filamentous cyanobacteria Trichodesmium spp. Near-surface ocean rates of N(2) fixation were 2-18 times greater (averaging 8.6+/-5.6 nmol N per l per day) than previously reported measurements at Station ALOHA. These results suggest that mesoscale physical variability can play an important role in modifying the abundances of N(2) fixing microorganisms and associated rates of N(2) fixation in open ocean ecosystems.
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PMID:Nitrogen fixation in an anticyclonic eddy in the oligotrophic North Pacific Ocean. 1830 59

Endotoxins are amphipathic lipopolysaccharides (LPSs), major constituents of the outer membrane of gram-negative bacteria. They consist of a lipid region, covalently linked to a core oligosaccharide, to which may be linked a repetitive glycosidic chain carrying antigenic determinants. Most of the biological activities of endotoxins have been associated with the lipid moiety of the molecule: unique to gram-negative bacteria, LPS is a ligand of the mammalian TLR4-MD2-CD14 pathogen recognition receptor complex. Lipid A preparations are often heterogeneous with respect to both the numbers and the lengths of fatty acids and the natures of substituents on the phosphate groups when present. The variants can significantly affect host immune responses. Nine species in the Bordetella genus have been described, and the fine LPS structures of seven of them have been published. In this report, lipids A from Bordetella pertussis Tohama I and B. bronchiseptica strain 4650 were further characterized and revealed to have a glucosamine substituting both lipid A phosphate groups of the diglucosamine backbone. These substitutions have not been previously described for bordetellae. Moreover, a B. pertussis transposon mutation that maps within a gene encoding a Bordetella ArnT (formerly PmrK) glycosyl transferase ortholog does not carry this substitution, thus providing a genetic basis for the modification. Reverse transcriptase PCR of this locus showed that it is Bvg regulated, suggesting that the ability of Bordetella to modify lipid A via this glucosamine modification is a potential virulence trait.
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PMID:Glucosamine found as a substituent of both phosphate groups in Bordetella lipid A backbones: role of a BvgAS-activated ArnT ortholog. 1842 15

Some Vibrio anguillarum strains produce a catechol-type siderophore named vanchrobactin, whose biosynthetic pathway has not been completely elucidated. In addition to the previously described genes vabA, vabC, vabB, vabE, vabF, vabS and vabH, in the present study we have identified the genes encoding a DAHP (3-deoxy-d-arabino-heptulosonate-7-phosphate) synthetase (vabG), a phosphopantheteinyl transferase (vabD), a LysR-family transcriptional regulator (vabR) and a putative siderophore receptor (fvtA). A deletion affecting vabG or vabD greatly reduced growth under iron-limiting conditions, whereas deletion of vabR did not have significant effects. Vanchrobactin production was abolished in the vabD mutant, whereas the vabG mutant retained a residual vanchrobactin production ability. Reverse transcriptase-mediated PCR indicated that this 11-gene cluster is organized into six iron-regulated transcriptional units. Transcriptional lacZ fusions demonstrated that the ferric uptake regulator (Fur) protein is the main iron-responsive regulator of these genes. Interestingly, the vabG gene was strongly iron-repressed, but Fur was not essential for this repression. In addition, the maximal expression from the vabG promoter was achieved only in the presence of an intact copy of vabR. Analysis of the beta-galactosidase activities of a fvtA : : lacZ fusion in a vabB mutant and in the presence of added vanchrobactin suggested that a ferric-vanchrobactin-dependent activator plays a positive regulatory role in transcription of the fvtA-vabD operon. This possibility is reinforced by the presence of a predicted AraC box upstream of fvtA. We propose that vanchrobactin biosynthesis is subjected to a complex regulatory circuitry aimed at adjusting vanchrobactin production for the maintenance of iron homeostasis in V. anguillarum.
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PMID:Biosynthetic and regulatory elements involved in the production of the siderophore vanchrobactin in Vibrio anguillarum. 1845 Oct 49

The RNA-dependent RNA polymerase L protein of vesicular stomatitis virus (VSV) elicits GTPase and RNA:GDP polyribonucleotidyltransferase (PRNTase) activities to produce a 5'-cap core structure, guanosine(5')triphospho(5')adenosine (GpppA), on viral mRNAs. Here, we report that the L protein produces an unusual cap structure, guanosine(5')tetraphospho(5')adenosine (GppppA), that is formed by the transfer of the 5'-monophosphorylated viral mRNA start sequence to GTP by the PRNTase activity before the removal of the gamma-phosphate from GTP by GTPase. Interestingly, GppppA-capped and polyadenylated full-length mRNAs were also found to be synthesized by an in vitro transcription system with the native VSV RNP.
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PMID:Formation of guanosine(5')tetraphospho(5')adenosine cap structure by an unconventional mRNA capping enzyme of vesicular stomatitis virus. 1849 67

Tobacco BY-2 suspension cells were used to study the chemical damage and its associated mechanisms caused by Cu2+. Treatment with 100 micromol/L Cu2+ generated a large amount of H2O2 and thiobarbituric acid-reactive substances (TBARS) in cells. Using phospholipase D (PLD) specific inhibitor (1-butanol) or phosphatidic acid (PA), we demonstrated that PLD plays an important role in the generation of H2O2 and TBARS. Semi-quantitative reverse-transcriptase polymerase chain reaction and enzyme activity assays with wild type and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-overexpressing BY-2 cells revealed that PLD and PA are the key factors leading to NADPH oxidase activation, which is responsible for H2O2 and TBARS production induced by Cu2+. Moreover, the content of ascorbic acid (AsA), an effective antioxidant, was sharply reduced in BY-2 cells exposed to excessive Cu2+. Furthermore, a significant downregulation of the enzymes of AsA biosynthesis and the antioxidant system was found. This evidence suggests that excessive Cu2+-elevated reactive oxygen species (ROS) production is caused by upregulated PLD that elevates the activity of NADPH oxidase and its collapsed antioxidant systems that scavenges ROS.
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PMID:Excessive copper induces the production of reactive oxygen species, which is mediated by phospholipase D, nicotinamide adenine dinucleotide phosphate oxidase and antioxidant systems. 1871 37


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