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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Perkinsus marinus is a protozoan parasite that causes high mortality in its commercially and ecologically important host, the Eastern oyster Crassostrea virginica. In order to understand the host-parasite relationship in lipid metabolism, the ability of P. marinus to synthesize phospholipids from polar headgroup precursors was investigated. Pulse/chase experiments were conducted using radiolabled serine, choline, ethanolamine and inositol. Timecourse incubations revealed that in vitro cultured P. marinus meronts can utilize the cytidine diphosphate-diacylglycerol (CDP-DAG) pathway to synthesize phosphatidylinositol (PI) from inositol and phosphatidylserine (PS) from serine. Serine label was also incorporated into phosphatidylethanolamine (PE), phosphatidylcholine (PC) and lysophosphatidylcholine (LPC). Incubations of P. marinus cells with increasing concentrations of radiolabeled serine resulted in more radioactivity recovered in neutral lipids than in polar lipids at the highest substrate concentration tested (344 microM). This suggests that excess serine label was being utilized for fatty acid synthesis and stored as triacylglycerols. Additional incubations were conducted with radiolabeled choline and ethanolamine at concentrations equimolar to the highest serine concentration tested. Ethanolamine label was also incorporated into PE, PS, PC and LPC. Choline label was incorporated into PC. These results suggest the presence of three pathways for de novo synthesis of phospholipids in P. marinus: CDP-choline, CDP-ethanolamine and CDP-DAG. At equivalent substrate concentrations (344 microM) the highest incorporation of labeled substrate into total phospholipids was with serine followed by ethanolamine and choline, respectively. P. marinus phospholipid biosynthetic capabilities appear to be similar to those of Plasmodium and Trypanosoma species.
Mol Biochem Parasitol 2002 May
PMID:Phospholipid biosynthesis in the oyster protozoan parasite, Perkinsus marinus. 1203 58

Intestinal gene regulation involves mechanisms that direct temporal expression along the vertical and horizontal axes of the alimentary tract. Sucrase-isomaltase (SI), the product of an enterocyte-specific gene, exhibits a complex pattern of expression. Generation of transgenic mice with a mutated SI transgene showed involvement of an overlapping CDP (CCAAT displacement protein)-GATA element in colonic repression of SI throughout postnatal intestinal development. We define this element as CRESIP (colon-repressive element of the SI promoter). Cux/CDP interacts with SI and represses SI promoter activity in a CRESIP-dependent manner. Cux/CDP homozygous mutant mice displayed increased expression of SI mRNA during early postnatal development. Our results demonstrate that an intestinal gene can be repressed in the distal gut and identify Cux/CDP as a regulator of this repression during development.
Mol Cell Biol 2002 Aug
PMID:A novel colonic repressor element regulates intestinal gene expression by interacting with Cux/CDP. 1210 Dec 40

Phosphatidylcholine and phosphatidylethanolamine are the two main phospholipids in eukaryotic cells comprising ~50 and 25% of phospholipid mass, respectively. Phosphatidylcholine is synthesized almost exclusively through the CDP-choline pathway in essentially all mammalian cells. Phosphatidylethanolamine is synthesized through either the CDP-ethanolamine pathway or by the decarboxylation of phosphatidylserine, with the contribution of each pathway being cell type dependent. Two human genes, CEPT1 and CPT1, code for the total compliment of activities that directly synthesize phosphatidylcholine and phosphatidylethanolamine through the CDP-alcohol pathways. CEPT1 transfers a phosphobase from either CDP-choline or CDP-ethanolamine to diacylglycerol to synthesize both phosphatidylcholine and phosphatidylethanolamine, whereas CPT1 synthesizes phosphatidylcholine exclusively. We show through immunofluorescence that brefeldin A treatment relocalizes CPT1, but not CEPT1, implying CPT1 is found in the Golgi. A combination of coimmunofluorescence and subcellular fractionation experiments with various endoplasmic reticulum, Golgi, and nuclear markers confirmed that CPT1 was found in the Golgi and CEPT1 was found in both the endoplasmic reticulum and nuclear membranes. The rate-limiting step for phosphatidylcholine synthesis is catalyzed by the amphitropic CTP:phosphocholine cytidylyltransferase alpha, which is found in the nucleus in most cell types. CTP:phosphocholine cytidylyltransferase alpha is found immediately upstream cholinephosphotransferase, and it translocates from a soluble nuclear location to the nuclear membrane in response to activators of the CDP-choline pathway. Thus, substrate channeling of the CDP-choline produced by CTP:phosphocholine cytidylyltransferase alpha to nuclear located CEPT1 is the mechanism by which upregulation of the CDP-choline pathway increases de novo phosphatidylcholine biosynthesis. In addition, a series of CEPT1 site-directed mutants was generated that allowed for the assignment of specific amino acid residues as structural requirements that directly alter either phospholipid head group or fatty acyl composition. This pinpointed glycine 156 within the catalytic motif as being responsible for the dual CDP-alcohol specificity of CEPT1, whereas mutations within helix 214-228 allowed for the orientation of transmembrane helices surrounding the catalytic site to be definitively positioned.
Mol Biol Cell 2002 Sep
PMID:The major sites of cellular phospholipid synthesis and molecular determinants of Fatty Acid and lipid head group specificity. 1222 Nov 22

The type 1 parathyroid hormone receptor (PTHR1) binds, with equal affinity, two ligands with distinct biological functions: PTH, the major peptide hormone controlling calcium homeostasis, and the paracrine factor, PTH-related peptide (PTHrP), a local regulator of cellular proliferation and differentiation. To clarify the complexity of possible interactions between two distinct ligands, PTH and PTHrP, and their common receptor in the intact organism, and to identify as yet unrecognized roles for PTH in normal physiology, we have cloned and characterized the structural organization, nucleotide sequence and transcriptional regulation of the murine gene encoding PTH. One recombinant clone isolated from a mouse genomic library contained 14 kb of DNA, encompassing the entire Pth gene. The transcriptional unit spans 3.2 kb of genomic DNA and, analogous to the human PTH gene, it is interrupted by two introns. The deduced mRNA encodes the 115-amino acid precursor, preproPTH. Comparison of the murine preproPTH sequence with other mammalian forms of the protein shows it to be highly conserved and to share limited structural similarity to PTHrP at the amino-terminal region, a domain critical for binding and activation of their common receptor. Putative binding motifs for the transcription factors sex-determining region Y gene product, transcriptional repressor CDP, hepatic nuclear factor 3beta, GATA-binding factor 1, glucocorticoid receptor, SRY-related high mobility group box protein 5 and cAMP response element binding protein were identified in the 5' flanking region of the Pth gene. When placed upstream of a reporter gene, these sequences failed to confer transcriptional regulation in response to 1,25(OH)(2) vitamin D(3), but responded positively to the addition of isoproterenol and forskolin. Mutational analysis identified a cAMP-response element in the Pth promoter.
J Mol Endocrinol 2002 Oct
PMID:The murine gene encoding parathyroid hormone: genomic organization, nucleotide sequence and transcriptional regulation. 1237 Jan 21

Rhabdomyosarcoma is a childhood tumor of the skeletal muscle lineage in which cells display defects in both biochemical and morphological aspects of differentiation. The immunoglobulin superfamily members CDO and BOC are components of a cell surface receptor that positively regulates myogenesis in vitro. Expression of Cdo and Boc in myoblast cell lines is downregulated by the ras oncogene, and forced re-expression of either Cdo or Boc can override ras-induced inhibition of myogenic differentiation [Kang et al., J Cell Biol 1998; 143:403-413; Kang et al., EMBO J 2002; 21:114-124]. The current study sought to test whether the promyogenic properties of CDO and BOC could be extended to a human rhabdomyosarcoma cell line, RD. Stable overexpression of CDO or BOC in RD cells led to enhanced expression of two markers of muscle cell differentiation, troponin T and myosin heavy chain, and to increased formation of elongated, myosin heavy chain-positive myotubes. These observations are consistent with the notion that CDO and BOC play a role in the inverse relationship between differentiation and transformation of cells in the skeletal muscle lineage.
Mol Carcinog 2003 May
PMID:Overexpression of the immunoglobulin superfamily members CDO and BOC enhances differentiation of the human rhabdomyosarcoma cell line RD. 1272 Feb 94

A novel host inclusion complex of beta-cyclodextrin-o-vanillin benzoylhydrazone (beta-CDP-OVBH) was prepared and characterized by IR and 1H-NMR spectra. A highly selective and sensitive fluorescent determination of trace amounts of zinc was proposed based on the reaction between Zn(2+) and beta-CDP-OVBH in sodium hydroxide-ammonium acetate buffer medium of pH 8.3. The molar ratio of beta-CDP-OVBH to Zn(2+) was 1:1. The maximum excitation and emission wavelengths were 396 and 486 nm, respectively. The linear range of this method was 2.5-500 microg l(-1) with a detection limit of 0.60 microg l(-1). The effect of interferences in the determination of zinc was investigated, the results showed that the host reagent had a quite high identifying capacity on Zn(2+). This method was successfully applied to the determination of trace amounts of Zn(2+) in tea and human hairs.
Spectrochim Acta A Mol Biomol Spectrosc 2003 Sep
PMID:Synthesis and characterization of a novel cross-linking complex of beta-cyclodextrin-o-vanillin benzoylhydrazone and its selective spectrofluorimetric determination of trace amounts of zinc. 1296 47

Various phosphodiesterase (PDE) 3,4 and 5 inhibitors have been compared with glucagon for their effectiveness at increasing hepatocyte cAMP, glycogenolysis and gluconeogenesis. Preincubation of isolated hepatocytes with PDE 3 and 4 inhibitors (50 microM) for 2 h induced significant increases in cellular cAMP level. The order of effectiveness was: glucagon (78%), V11294A (42%), rolipram (40%), milrinone (36%), CDP-840 (33%), R(0) 20-1724 (31%), papaverine (27%), isobutylmethylxanthine (28%), isoliquiritigenin (25%), theophylline (22%), and amrinone (22%). The PDE 5 inhibitors dipyridamol and sildenafil had only a slight effect on cAMP levels. Glucose formation was increased as a result of increased glycogenolysis in the following order of effectiveness: glucagon (89%), V11294A (63%), rolipram (61%), milrinone (50%), CDP-840 (46%), R(0) 20-1724 (45%), sildenafil (34%), dipyridamol (31%), papaverine (30%), isobutylmethylxanthine (29%), theophylline (20%), amrinone (20%), and isoliquiritigenin (20%). Rolipram and milrinone, selective PDE 4 and PDE 3 inhibitors respectively, stimulated the gluconeogenesis of alanine, lactate + pyruvate, or fructose in hepatocytes isolated from fasted rats. On the other hand, selective cGMP specific phospodiesterase inhibitors, sildenafil and dipyridamol inhibited alanine-induced gluconeogenesis. All PDE inhibitors increased hepatocyte susceptibility to cyanide toxicity (3-4 fold) which was prevented by fructose whereas PDE 5 inhibitors did not significantly increase hepatocyte susceptibility.
Mol Cell Biochem 2003 Oct
PMID:Effects of phosphodiesterase 3,4,5 inhibitors on hepatocyte cAMP levels, glycogenolysis, gluconeogenesis and susceptibility to a mitochondrial toxin. 1457 94

In this review, the pathways for phosphatidylserine (PS) and phosphatidylethanolamine (PE) biosynthesis, as well as the genes and proteins involved in these pathways, are described in mammalian cells, yeast, and prokaryotes. In mammalian cells, PS is synthesized by a base-exchange reaction in which phosphatidylcholine or PE is substrate for PS synthase-1 or PS synthase-2, respectively. Isolation of Chinese hamster ovary cell mutants led to the cloning of cDNAs and genes encoding these two PS synthases. In yeast and prokaryotes PS is produced by a biosynthetic pathway completely different from that in mammals: from a reaction between CDP-diacylglycerol and serine. The major route for PE synthesis in cultured cells is from the mitochondrial decarboxylation of PS. Alternatively, PE can be synthesized in the endoplasmic reticulum (ER) from the CDP-ethanolamine pathway. Genes and/or cDNAs encoding all the enzymes in these two pathways for PE synthesis have been isolated and characterized. In mammalian cells, PS is synthesized on the ER and/or mitochondria-associated membranes (MAM). PS synthase-1 and -2 are highly enriched in MAM compared to the bulk of ER. Since MAM are a region of the ER that appears to be in close juxtaposition to the mitochondrial outer membrane, it has been proposed that MAM act as a conduit for the transfer of newly synthesized PS into mitochondria. A similar pathway appears to operate in yeast. The use of yeast mutants has led to identification of genes involved in the interorganelle transport of PS and PE in yeast, but so far none of the corresponding genes in mammalian cells has been identified. PS and PE do not act solely as structural components of membranes. Several specific functions have been ascribed to these two aminophospholipids. For example, cell-surface exposure of PS during apoptosis is thought to be the signal by which apoptotic cells are recognized and phagocytosed. Translocation of PS from the inner to outer leaflet of the plasma membrane of platelets initiates the blood-clotting cascade, and PS is an important activator of several enzymes, including protein kinase C. Recently, exposure of PE on the cell surface was identified as a regulator of cytokinesis. In addition, in Escherichia coli, PE appears to be involved in the correct folding of membrane proteins; and in Drosophila, PE regulates lipid homeostasis via the sterol response element-binding protein.
Prog Nucleic Acid Res Mol Biol 2003
PMID:Molecular and cell biology of phosphatidylserine and phosphatidylethanolamine metabolism. 1460 10

Block buster drugs share a variety of common features, among which is the tendency to create entirely new markets. For example, an early "informed" estimate of the potential market size for the hypothetically "perfect" peptic ulcer drug was thirty-five million dollars. Based on current sales, however, we reckon this hypothesis to have underestimated the actual market demand for omeprazole (Prilosec) by about 400-fold. Similarly, prior to the introduction of the "retired" block busters chlordiazepoxide and diazepam (Librium and Valium), the market for "minor tranquilizers" in the treatment of anxiety and neurosis did not exist. Thus, once an emerging block buster seems to be therapeutically working, it is not unusual for diagnostic rates of the disease for which it is indicated and efficacious to actually increase. Top block buster drugs generally have or appear to have a high margin of safety.
Mol Interv 2002 Feb
PMID:Life cycle of a block buster drug: discovery and development of omeprazole (Prilosec). 1499 56

A novel host inclusion complex of cross-linking-polymeric-beta-cyclodextrin-o-vanillin furfuralhydrazone (beta-CDP-OVFH) was synthesized and characterized with IR and 1H NMR spectra to confirm its structure. The coordination reaction of the host reagent with Cd(2+) was studied and the optimum reacting conditions were observed carefully. A highly selective and sensitive spectrofluorimetric determination of trace amount of cadmium was proposed based on the reaction of Cd(2+) with beta-CDP-OVFH in ammonia water-ammonium acetate buffer medium of pH = 11.0. The molar ratio of beta-CDP-OVFH to Cd(2+) was 1:1. The maximum excitation and emission wavelengths were 393 and 494 nm, respectively. The linear range of this method was from 3.0 to 500 microg l(-1) with a detection limit of 0.80 microg l(-1). The effect of interferences in the determination of cadmium was investigated and the results showed that the host reagent had quite high capacity of identifying Cd(2+). The proposed method was successfully applied to the determination of trace amount of Cd(2+) in mussel and tea samples.
Spectrochim Acta A Mol Biomol Spectrosc 2004 Aug
PMID:Synthesis of a novel host molecule of cross-linking-polymeric-beta-cyclodextrin-o-vanillin furfuralhydrazone and spectrofluorimetric analysis of its identifying cadmium. 1524 35


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