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Your search keyword '"Ribeiro, Anthony A."' showing total 250 results
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250 results on '"Ribeiro, Anthony A."'

1. Kdo2-Lipid A of Escherichia coli, a defined endotoxin that activates macrophages via TLR-4

Author

Raetz, Christian RH, Garrett, Teresa A, Reynolds, C Michael, Shaw, Walter A, Moore, Jeff D, Smith, Dale C, Ribeiro, Anthony A, Murphy, Robert C, Ulevitch, Richard J, Fearns, Colleen, Reichart, Donna, Glass, Christopher K, Benner, Chris, Subramaniam, Shankar, Harkewicz, Richard, Bowers-Gentry, Rebecca C, Buczynski, Matthew W, Cooper, Jennifer A, Deems, Raymond A, and Dennis, Edward A

Subjects
Biochemistry and Cell Biology, Biomedical and Clinical Sciences, Biological Sciences, Underpinning research, 1.1 Normal biological development and functioning, Animals, Chromatography, High Pressure Liquid, Escherichia coli, Lipopolysaccharides, Macrophage Activation, Mice, Nuclear Magnetic Resonance, Biomolecular, Prostaglandin D2, Spectrometry, Mass, Electrospray Ionization, Toll-Like Receptor 4, 3-deoxy-D-manno-octulosonic acid-Lipid A, Re, endotoxin, macrophage, mass spectrometry, LIPID MAPS, toll-like receptor-4, Medical Biochemistry and Metabolomics, Biochemistry & Molecular Biology, Biochemistry and cell biology, Medical biochemistry and metabolomics
Abstract

The LIPID MAPS Consortium (www.lipidmaps.org) is developing comprehensive procedures for identifying all lipids of the macrophage, following activation by endotoxin. The goal is to quantify temporal and spatial changes in lipids that occur with cellular metabolism and to develop bioinformatic approaches that establish dynamic lipid networks. To achieve these aims, an endotoxin of the highest possible analytical specification is crucial. We now report a large-scale preparation of 3-deoxy-D-manno-octulosonic acid (Kdo)(2)-Lipid A, a nearly homogeneous Re lipopolysaccharide (LPS) sub-structure with endotoxin activity equal to LPS. Kdo(2)-Lipid A was extracted from 2 kg cell paste of a heptose-deficient Escherichia coli mutant. It was purified by chromatography on silica, DEAE-cellulose, and C18 reverse-phase resin. Structure and purity were evaluated by electrospray ionization/mass spectrometry, liquid chromatography/mass spectrometry and (1)H-NMR. Its bioactivity was compared with LPS in RAW 264.7 cells and bone marrow macrophages from wild-type and toll-like receptor 4 (TLR-4)-deficient mice. Cytokine and eicosanoid production, in conjunction with gene expression profiling, were employed as readouts. Kdo(2)-Lipid A is comparable to LPS by these criteria. Its activity is reduced by >10(3) in cells from TLR-4-deficient mice. The purity of Kdo(2)-Lipid A should facilitate structural analysis of complexes with receptors like TLR-4/MD2.

Published
2006

7. Dendritic molecular capsules for hydrophobic compounds

Author

Morgan, Meredith T., Carnahan, Michael A., Immoos, Chad E., Ribeiro, Anthony A., Finkelstein, Stella, Lee, Stephen J., and Grinstaff, Mark W.

Subjects
Hydrophobic effect -- Analysis, Absorption -- Usage, Dyes and dyeing -- Chemical properties, Dendrimers -- Research, Dendrimers -- Chemical properties, Chemistry
Abstract

Close through-space proximity of the dye to the dendrimer and the restricted motion of the encapsulated dye are revealed. Cytotoxicity assays with human breast cancer cells showed a significant reduction of cell viability, demonstrating that 10HCPT retains activity upon encapsulation.

Published
2003

8. (super)31 P NMR probes of chemical dynamics: paramagnetic relaxation enhancement of the (super)1 H and (super)31 P NMR resonances of methyl phosphite and methylethyl phosphate anions by selected metal complexes

Author

Summers, Jack S., Hoogstraten, Charles G., Britt, R. David, Base, Karel, Shaw, Barbara Ramsay, Ribeiro, Anthony A., and Crumbliss, Alvin L.

Subjects
Chemistry, Inorganic -- Research, Phosphates -- Physiological aspects, Anions -- Physiological aspects, Coordination compounds -- Physiological aspects, Metal ions -- Physiological aspects, Chemistry
Abstract

Research has been conducted on the methyl phosphite and methylethyl phosphate. Results indicate that these compounds may be used as probes of the paramagnetic metal ion reactivities toward the inner shell coordination exchange without the studies of the variable temperatures.

Published
2001

10. Structure and conformations of monoacyl and diacyl 1,2,4-triazolidine-3,5-diones

Author

Izydore, Robert A., Ribeiro, Anthony A., and Hall, Iris H.

Subjects
Organic compounds -- Research, Biological sciences, Chemistry
Abstract

The acylations of 4-substituted 1,2,4-triazolidine-3,5-diones using a phenyl or a tert-butyl group were investigated. Specifically, H, 13C and 15 N nuclear magnetic resonance spectroscopy was employed to examine the conformational geometry of the acetyl and benzoyl groups which acted as acyl substituents. According to results, acylation was exclusive to the ring nitrogen atoms and all O-acyl, O,O-diacyl and N,O-diacyl groups were absent in all the compounds.

Published
1996

11. Total synthesis of d,l-isospongiadiol: an intramolecular radical cascade approach to furanoditerpenes

Author

Zoretic, Phillip A., Wang, Ming, Zhang, Yongzheng, Shen, Zhongqi, and Ribeiro, Anthony A.

Subjects
Organic compounds -- Synthesis, Terpenes -- Research, Biological sciences, Chemistry
Abstract

The synthesis of d,l-isospongiadiol is described. The scheme involves the stereoselective oxidative free-radical cyclization of beta-keto ester polyenes to form the tricarboxylic synthons containing five and six stereogenic centers. These synthons were converted to the spongian skeleton. Introduction of the 2alpha-hydroxy group in the spongian A-ring via epoxidation of silyl enol ether and subsequent silylation afford the target compound.

Published
1996

17. Identification of undecaprenyl phosphate-[beta]-D-galactosamine in Francisella novicida and its function in lipid A modification

Author

Xiaoyuan Wang, Ribeiro, Anthony A., Ziqiang Guan, and Raetz, Christian R.H.

Subjects
Amines -- Chemical properties, Francisella tularensis -- Physiological aspects, Lipid membranes -- Composition, Phosphates -- Chemical properties, Biological sciences, Chemistry
Abstract

The purification and identification of a novel minor lipid from tularemia causing Francisella novicida, a highly infectious pathogen that functions as the galactosamine (GalN) donor is reported. The identification of undecaprenyl phosphate-[beta]-D-GalN indicated that Francisella modifies lipid A with GalN on the periplasmic surface of the inner membrane.

Published
2009

18. Structure and biosynthesis of free lipid A molecules that replace lipopolysaccharide in Francisella tularensis subsp. novicida

Author

Xiaoyuan Wang, Ribeiro, Anthony A., Ziqiang Guan, McGrath, Sara C., Cotter, Robert J., and Raetz, Christian R.H.

Subjects
Lipids -- Physiological aspects, Biosynthesis -- Analysis, Microbial polysaccharides -- Research, Biological sciences, Chemistry
Abstract

Two lipid species designated as A1 and A2 found in Francisella (F) tularensis subsp. novicida U112 phospholipids were analyzed by electroscopy ionization and matrix-assisted laser desorption ionization mass spectrometry, gas chromatography/mass spectrometry and NMR spectroscopy. It is shown that lipid A from the live vaccine strain of F. tularensis is present mostly in the free form and proposed that free lipid A may arise from nascent lipopolysaccharide by a novel system of extracellular remodeling enzymes.

Published
2006

21. Synthesis and characterization of carbohydrate-based phospholipids

Author

Hird, Geoffrey S., McIntosh, Thomas J., Ribeiro, Anthony A., and Grinstaff, Mark W.

Subjects
Glycerin -- Research, Glycerin -- Chemical properties, Glycerol -- Research, Glycerol -- Chemical properties, Carbohydrates -- Research, Carbohydrates -- Chemical properties, Phospholipids -- Research, Phospholipids -- Chemical properties, Chemistry
Abstract

The synthesis and physical properties of the carbohydrate-based phospholipid, dimyristoyl ribo-phosphocholine (DMRPC) and diarachadonyl ribo-phosphocholine (DARPC) is depicted. The physical property relationship between new carbohydrated-based C12, C14 and C20 phospholipids and the corresponding glycerol analogues are discussed.

Published
2002

22. Targeting the lactate transporter MCT1 in endothelial cells inhibits lactate-induced angiogenesis

Author

UCL - SSS/IREC/FATH - Pôle de Pharmacologie et thérapeutique, UCL - SSS/LDRI - Louvain Drug Research Institute, FUNDP - SBIO_URBM (unité de recherche en biologie moléculaire), Copetti, Tamara, De Saedeleer, Christophe, Vegran, Frédérique, Verrax, Julien, Kennedy, Kelly M, Moon, Eui J, Dhup, Suveera, Danhier, Pierre, Frérart, Françoise, Gallez, Bernard, Ribeiro, Anthony, Michiels, Carine, Dewhirst, Mark W, Feron, Olivier, Sonveaux, Pierre, 4th annual meeting of the ISPDC, UCL - SSS/IREC/FATH - Pôle de Pharmacologie et thérapeutique, UCL - SSS/LDRI - Louvain Drug Research Institute, FUNDP - SBIO_URBM (unité de recherche en biologie moléculaire), Copetti, Tamara, De Saedeleer, Christophe, Vegran, Frédérique, Verrax, Julien, Kennedy, Kelly M, Moon, Eui J, Dhup, Suveera, Danhier, Pierre, Frérart, Françoise, Gallez, Bernard, Ribeiro, Anthony, Michiels, Carine, Dewhirst, Mark W, Feron, Olivier, Sonveaux, Pierre, and 4th annual meeting of the ISPDC

Published
2014

25. Catabolism of exogenous lactate reveals it as a legitimate metabolic substrate in breast cancer

Author

UCL - SSS/IREC/FATH - Pôle de Pharmacologie et thérapeutique, UCL - SSS/IREC - Institut de recherche expérimentale et clinique, Kennedy, Kelly M, Scarbrough, Peter M, Ribeiro, Anthony, Richardson, Rachel, Yuan, Hong, Sonveaux, Pierre, Landon, Chelsea D, Chi, Jen-Tsan, Pizzo, Salvatore, Schroeder, Thies, Dewhirst, Mark W, UCL - SSS/IREC/FATH - Pôle de Pharmacologie et thérapeutique, UCL - SSS/IREC - Institut de recherche expérimentale et clinique, Kennedy, Kelly M, Scarbrough, Peter M, Ribeiro, Anthony, Richardson, Rachel, Yuan, Hong, Sonveaux, Pierre, Landon, Chelsea D, Chi, Jen-Tsan, Pizzo, Salvatore, Schroeder, Thies, and Dewhirst, Mark W

Abstract

Lactate accumulation in tumors has been associated with metastases and poor overall survival in cancer patients. Lactate promotes angiogenesis and metastasis, providing rationale for understanding how it is processed by cells. The concentration of lactate in tumors is a balance between the amount produced, amount carried away by vasculature and if/how it is catabolized by aerobic tumor or stromal cells. We examined lactate metabolism in human normal and breast tumor cell lines and rat breast cancer: 1. at relevant concentrations, 2. under aerobic vs. hypoxic conditions, 3. under conditions of normo vs. hypoglucosis. We also compared the avidity of tumors for lactate vs. glucose and identified key lactate catabolites to reveal how breast cancer cells process it. Lactate was non-toxic at clinically relevant concentrations. It was taken up and catabolized to alanine and glutamate by all cell lines. Kinetic uptake rates of lactate in vivo surpassed that of glucose in R3230Ac mammary carcinomas. The uptake appeared specific to aerobic tumor regions, consistent with the proposed '‘metabolic symbiont’’ model; here lactate produced by hypoxic cells is used by aerobic cells. We investigated whether treatment with alpha-cyano-4-hydroxycinnamate (CHC), a MCT1 inhibitor, would kill cells in the presence of high lactate. Both 0.1 mM and 5 mM CHC prevented lactate uptake in R3230Ac cells at lactate concentrations at #20 mM but not at 40 mM. 0.1 mM CHC was well-tolerated by R3230Ac and MCF7 cells, but 5 mM CHC killed both cell lines 6 lactate, indicating off-target effects. This study showed that breast cancer cells tolerate and use lactate at clinically relevant concentrations in vitro (6 glucose) and in vivo. We provided additional support for the metabolic symbiont model and discovered that breast cells prevailingly take up and catabolize lactate, providing rationale for future studies on manipulation of lactate catabolism pathways for therapy.

Published
2013

26. Targeting the lactate transporter MCT1 in endothelial cells inhibits lactate-induced HIF-1 activation and tumor angiogenesis

Author

UCL - SSS/IREC/FATH - Pôle de Pharmacologie et thérapeutique, UCL - SSS/LDRI - Louvain Drug Research Institute, Sonveaux, Pierre, Copetti, Tamara, De Saedeleer, Christophe, Végran, Frédérique, Verrax, Julien, Kennedy, Kelly M, Moon, Eui Jung, Dhup, Suveera, Danhier, Pierre, Frérart, Françoise, Gallez, Bernard, Ribeiro, Anthony, Michiels, Carine, Dewhirst, Mark W, Feron, Olivier, UCL - SSS/IREC/FATH - Pôle de Pharmacologie et thérapeutique, UCL - SSS/LDRI - Louvain Drug Research Institute, Sonveaux, Pierre, Copetti, Tamara, De Saedeleer, Christophe, Végran, Frédérique, Verrax, Julien, Kennedy, Kelly M, Moon, Eui Jung, Dhup, Suveera, Danhier, Pierre, Frérart, Françoise, Gallez, Bernard, Ribeiro, Anthony, Michiels, Carine, Dewhirst, Mark W, and Feron, Olivier

Abstract

Switching to a glycolytic metabolism is a rapid adaptation of tumor cells to hypoxia. Although this metabolic conversion may primarily represent a rescue pathway to meet the bioenergetic and biosynthetic demands of proliferating tumor cells, it also creates a gradient of lactate that mirrors the gradient of oxygen in tumors. More than a metabolic waste, the lactate anion is known to participate to cancer aggressiveness, in part through activation of the hypoxia-inducible factor-1 (HIF-1) pathway in tumor cells. Whether lactate may also directly favor HIF-1 activation in endothelial cells (ECs) thereby offering a new druggable option to block angiogenesis is however an unanswered question. In this study, we therefore focused on the role in ECs of monocarboxylate transporter 1 (MCT1) that we previously identified to be the main facilitator of lactate uptake in cancer cells. We found that blockade of lactate influx into ECs led to inhibition of HIF-1-dependent angiogenesis. Our demonstration is based on the unprecedented characterization of lactate-induced HIF-1 activation in normoxic ECs and the consecutive increase in vascular endothelial growth factor receptor 2 (VEGFR2) and basic fibroblast growth factor (bFGF) expression. Furthermore, using a variety of functional assays including endothelial cell migration and tubulogenesis together with in vivo imaging of tumor angiogenesis through intravital microscopy and immunohistochemistry, we documented that MCT1 blockers could act as bona fide HIF-1 inhibitors leading to anti-angiogenic effects. Together with the previous demonstration of MCT1 being a key regulator of lactate exchange between tumor cells, the current study identifies MCT1 inhibition as a therapeutic modality combining antimetabolic and anti-angiogenic activities.

Published
2012

27. Two-dimensional NMR Spectroscopy and Structures of Six Lipid A Species from Rhizobium etli CE3 DETECTION OF AN ACYLOXYACYL RESIDUE IN EACH COMPONENT AND ORIGIN OF THE AMINOGLUCONATE MOIETY*S

Author

Que, Nanette L. S., Ribeiro, Anthony A., and Raetz, Christian R. H.

Subjects
Glucosamine, Lipid A, Carbohydrate Sequence, Gram-Negative Bacteria, Molecular Sequence Data, Carbohydrate Conformation, Molecular Conformation, Hydroxybutyrates, Chromatography, Thin Layer, Gluconates, Nuclear Magnetic Resonance, Biomolecular, Article, Rhizobium
Abstract

The chemical structures of six lipid A species (A, B, C, D-1, D-2, and E) purified from Rhizobium etli CE3 were investigated by one- and two-dimensional NMR spectroscopy. The R. etli lipid A subtypes each contain an unusual acyloxyacyl residue at position 2' as part of a conserved distal glucosamine moiety but differ in their proximal units. All R. etli lipid A species lack phosphate groups. However, they are derivatized with an alpha-linked galacturonic acid group at position 4', as shown by nuclear Overhauser effect spectroscopy. Component B, which had been not been reported in previous studies, features a beta, 1'-6 linked disaccharide of glucosamine acylated at positions 2, 3, 2', and 3' in a pattern that is typical of lipid A found in other Gram-negative bacteria. D-1 contains an acylated aminogluconate unit in place of the proximal glucosamine residue of B. C and E lack ester-linked beta-hydroxyacyl chains at position 3, as judged by their H-3 chemical shifts, and may be synthesized from B and D-1, respectively, by the R. etli 3-O-deacylase. D-2 is an isomer of D-1 that forms nonenzymatically by acyl chain migration. A may be an elimination product derived from D-1 during hydrolysis at 100 degrees C (pH 4.5), a step needed to release lipid A from lipopolysaccharide. Based on these findings, we propose a biosynthetic scheme for R. etli lipid A in which B is generated first by a variation of the E. coli pathway. The aminogluconate unit of D-1 could then be made from B by enzymatic oxidation of the proximal glucosamine. As predicted by our hypothesis, enzyme(s) can be demonstrated in extracts of R. etli that convert (14)C-labeled B to D-1.

Published
2000

31. Targeting the Lactate Transporter MCT1 in Endothelial Cells Inhibits Lactate-Induced HIF-1 Activation and Tumor Angiogenesis

Author

Sonveaux, Pierre, primary, Copetti, Tamara, additional, De Saedeleer, Christophe J., additional, Végran, Frédérique, additional, Verrax, Julien, additional, Kennedy, Kelly M., additional, Moon, Eui Jung, additional, Dhup, Suveera, additional, Danhier, Pierre, additional, Frérart, Françoise, additional, Gallez, Bernard, additional, Ribeiro, Anthony, additional, Michiels, Carine, additional, Dewhirst, Mark W., additional, and Feron, Olivier, additional

Published
2012
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