24 results on '"Gonzalez-Nunez V"'
Search Results
2. List of Contributors
- Author
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Alves, C.J., primary, Anglard, P., additional, Anier, K., additional, Armstrong, R.A., additional, Bachtell, R.K., additional, Bakshi, K., additional, Barbanti, P., additional, Barrio, P., additional, Batalla, A., additional, Becker, J.B., additional, Bekker, A., additional, Benkelfat, C., additional, Bergman, J., additional, Bhattacharya, P., additional, Bisagno, Veronica, additional, Brimijoin, S., additional, Brown, Z.J., additional, Buffalari, D., additional, Bühler, K.-M., additional, Caffino, L., additional, Cafforio, G., additional, Camarini, R., additional, Carvalho, V.M., additional, Cepko, L.C.S., additional, Chen, C.-C., additional, Chu, X.-P., additional, Corbit, L.H., additional, Crofton, E.J., additional, Crunelle, C.L., additional, Cunha, P.J., additional, Cunha-Oliveira, T., additional, Currie, P.J., additional, D’Ascenzo, M., additional, Dieckmann, L.H.J., additional, von Diemen, L., additional, Dumont, E.C., additional, Eagle, A.L., additional, Eipper, B.A., additional, Eipper-Mains, J.E., additional, Engeln, M., additional, Erb, S., additional, Farré, A., additional, Farré, M., additional, Felts, A.S., additional, Fofi, L., additional, Foster, J.D., additional, Fox, H.C., additional, Frankfurt, M., additional, Freissmuth, M., additional, Fuchs, R.A., additional, Fumagalli, F., additional, Gajewski, P.A., additional, Galaj, E., additional, Galduróz, J.C.F., additional, Garling, E.E., additional, Gentile, T.A., additional, Giannotti, G., additional, Girault, J.-A., additional, Glass, J.D., additional, Goncalves, P.D., additional, González-Duarte, A., additional, Gonzalez-Nunez, V., additional, Gould, R.W., additional, Grassi, C., additional, Green, T.A., additional, Green-Sadan, T., additional, Gu, H.H., additional, Guan, Xiaowei, additional, Halbout, B., additional, Han, D.D., additional, Henry, L.K., additional, Pérez de Heredia, J.L., additional, Higginbotham, J.A., additional, Hofmaier, T., additional, Holy, M., additional, Hsu, K.-S., additional, Huang, C.-C., additional, James, J., additional, Jones, A.W., additional, Jones, C.K., additional, Kalda, A., additional, Kearns, D.N., additional, Kerver, H.N., additional, Kessler, F., additional, Kohut, S.J., additional, Krnjević, K., additional, Kucab, P., additional, Kudlacek, O., additional, Kupferschmidt, D.A., additional, Kuzhikandathil, E.V., additional, Lee, M.R., additional, Leggio, L., additional, Lever, J.R., additional, Lever, S.Z., additional, Leyton, M., additional, Li, J.-X., additional, Lima, D.R., additional, Lobo, M.K., additional, López-Moreno, J.A., additional, López-Pelayo, H., additional, Lovejoy, D.A., additional, Luf, A., additional, Lugon, M.D.M.V., additional, Lyons, C.E., additional, Magalhães, A., additional, Magalhães, P.V.S., additional, Mainardi, M., additional, Mains, R.E., additional, Mantsch, J.R., additional, Marcourakis, T., additional, Marhe, R., additional, Matthys, F., additional, El Mestikawy, S., additional, Milivojevic, V., additional, Miller, D.K., additional, Min, M.O., additional, Minnes, S., additional, Mitchell, M.R., additional, Monteiro, P.R., additional, Murthy, V., additional, Muschamp, J.W., additional, Nagy, C., additional, Nakamura-Palacios, E.M., additional, Narvaez, J.C.M., additional, Normandeau, C.P., additional, Ornell, F., additional, Orsini, C.A., additional, Ostlund, S.B., additional, Otkins, J., additional, Patel, V.B., additional, Pelição, F.S., additional, Pereira, S.P., additional, Peres, M.D., additional, Potenza, M.N., additional, Preedy, V.R., additional, Prosser, R.A., additional, Quednow, B.B., additional, Rajendram, R., additional, Ramos, A.C., additional, Ranaldi, R., additional, Rangel-Barajas, C., additional, Rebec, G.V., additional, Robison, A.J., additional, Rodríguez, R.E., additional, Rohn, M.C.H., additional, Roth-Deri, I., additional, Scala, S.G., additional, Scavone, C., additional, Schellekens, A., additional, Scherer, J., additional, Schmid, R., additional, Scurlock, R.D., additional, Setlow, B., additional, Simmons, S.J., additional, Singer, L.T., additional, Sinha, R., additional, Sitte, H.H., additional, Smart, K., additional, Stockner, T., additional, Summavielle, T., additional, Szumlinski, K.K., additional, Tanda, G., additional, Torrens, M., additional, Tunstall, B.J., additional, Urbano, F.J., additional, Vaughan, R.A., additional, Verhaeghe, M., additional, Vonmoos, M., additional, Wagner, J.J., additional, Wang, Y., additional, Xi, Z.-X., additional, Xu, Y., additional, Yadid, G., additional, Ye, J.-H., additional, Yoon, S., additional, Zallar, L.J., additional, Zhan, Chang-Guo, additional, Zhang, H.-Y., additional, Zhang, Y., additional, Zheng, Fang, additional, Zuo, W., additional, and Zwiller, J., additional more...
- Published
- 2017
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Catalog
3. Identification of dynorphin a from zebrafish: A comparative study with mammalian dynorphin A
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Gonzalez-Nuñez, V., Marrón Fernández de Velasco, E., Arsequell, G., Valencia, G., and Rodríguez, R.E.
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- 2007
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4. Characterization of zebrafish proenkephalin reveals novel opioid sequences
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Gonzalez Nuñez, V., Gonzalez Sarmiento, R., and Rodrı́guez, R.E.
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- 2003
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5. Conceptos básicos de la estructura génica. Regulación de la expresión génica
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Rivas Boyero, A., Rodríguez Martín, I., González Nuñez, V., and Rodríguez Rodríguez, R.E.
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- 2002
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6. Chapter 12 - Cocaine and Transcription Factors
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Gonzalez-Nunez, V. and Rodríguez, R.E.
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- 2017
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7. Pharmacological characterization of a nociceptin receptor from zebrafish (Danio rerio)
- Author
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Rivas-Boyero, A. A., primary, Herrero-Turrion, M. J., additional, Gonzalez-Nunez, V., additional, Sanchez-Simon, F. M., additional, Barreto-Valer, K., additional, and Rodriguez, R. E., additional
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- 2011
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8. The Zebrafish: A Model to Study the Endogenous Mechanisms of Pain
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Gonzalez-Nunez, V., primary and Rodriguez, R. E., additional
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- 2009
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9. Identification of two proopiomelanocortin genes in zebrafish (Danio rerio)
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Gonzalez Nunez, V, primary
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- 2003
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10. Cloning and characterization of a full-length pronociceptin in zebrafish: evidence of the existence of two different nociceptin sequences in the same precursor
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Gonzalez-Nunez, V, primary
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- 2003
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11. Evolution of Fentanyl Prescription Patterns and Administration Routes in Primary Care in Salamanca, Spain: A Comprehensive Analysis from 2011 to 2022.
- Author
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Torres-Bueno C, Sanchez-Barba M, Miron-Canelo JA, and Gonzalez-Nunez V
- Abstract
(1) Background: The escalating use of opioids contributes to social, health, and economic crises. In Spain, a notable surge in the medical prescription of opioids in recent years has been observed. The aim of this work was to assess the consumption rate of fentanyl, categorised by the different administration routes, in Primary Care in the province of Salamanca (Spain) spanning the years 2011 to 2022, and to compare it with the national trend and with data from the US. (2) Methods: Doses per inhabitant per day (DHD) were calculated, and interannual variations, as well as consumption rates, were subject to thorough analysis. (3) Results: The prevalence of fentanyl use in Salamanca has doubled from 1.21 DHD in 2011 to 2.56 DHD in 2022, with the transdermal system (TD) as the predominant administration route. This upward trajectory mirrors the national trend, yet the rise in fentanyl use is markedly lower than the reported data in the US. This finding may be attributed to an ageing population and potentially inappropriate fentanyl prescriptions, i.e., for the management of chronic non-cancer pain and other off-label prescriptions. (4) Conclusions: The use of fentanyl in Salamanca, particularly through transdermal systems, doubled from 2011 to 2022, aligning with the national trend. Preventive measures are imperative to prevent fentanyl misuse and moderate the observed escalation in consumption rates. more...
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- 2024
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12. Exposure to Morphine and Cocaine Modify the Transcriptomic Landscape in Zebrafish Embryos.
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Calderon-Garcia AA, Perez-Fernandez M, Curto-Aguilera D, Rodriguez-Martin I, Sánchez-Barba M, and Gonzalez-Nunez V
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- Animals, Zebrafish metabolism, Transcriptome, Receptors, Opioid metabolism, Morphine pharmacology, Cocaine pharmacology
- Abstract
Morphine and other opioid analgesics are the drugs of election to treat moderate-to-severe pain, and they elicit their actions by binding to the opioid receptors. Cocaine is a potent inhibitor of dopamine, serotonin, and noradrenaline reuptake, as it blocks DAT, the dopamine transporter, causing an increase in the local concentration of these neurotransmitters in the synaptic cleft. The molecular effects of these drugs have been studied in specific brain areas or nuclei, but the systemic effects in the whole organism have not been comprehensively analyzed. This study aims to analyze the transcriptomic changes elicited by morphine (10 uM) and cocaine (15 uM) in zebrafish embryos. An RNAseq assay was performed with tissues extracts from zebrafish embryos treated from 5 hpf (hours post fertilization) to 72 hpf, and the most representative deregulated genes were experimentally validated by qPCR. We have found changes in the expression of genes related to lipid metabolism, chemokine receptor ligands, visual system, hemoglobins, and metabolic detoxification pathways. Besides, morphine and cocaine modified the global DNA methylation pattern in zebrafish embryos, which would explain the changes in gene expression elicited by these two drugs of abuse., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.) more...
- Published
- 2022
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13. Doublecortin in the Fish Visual System, a Specific Protein of Maturing Neurons.
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DeOliveira-Mello L, Vicente I, Gonzalez-Nunez V, Santos-Ledo A, Velasco A, Arévalo R, Lara JM, and Mack AF
- Abstract
Doublecortin (DCX) is a microtubule associated protein, essential for correct central nervous system development and lamination in the mammalian cortex. It has been demonstrated to be expressed in developing-but not in mature-neurons. The teleost visual system is an ideal model to study mechanisms of adult neurogenesis due to its continuous life-long growth. Here, we report immunohistochemical, in silico , and western blot analysis to detect the DCX protein in the visual system of teleost fish. We clearly determined the expression of DCX in newly generated cells in the retina of the cichlid fish Astatotilapia burtoni , but not in the cyprinid fish Danio rerio . Here, we show that DCX is not associated with migrating cells but could be related to axonal growth. This work brings to light the high conservation of DCX sequences between different evolutionary groups, which make it an ideal marker for maturing neurons in various species. The results from different techniques corroborate the absence of DCX expression in zebrafish. In A. burtoni , DCX is very useful for identifying new neurons in the transition zone of the retina. In addition, this marker can be applied to follow axons from maturing neurons through the neural fiber layer, optic nerve head, and optic nerve. more...
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- 2022
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14. Male reproductive dysfunction in Solea senegalensis: new insights into an unsolved question.
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Riesco MF, Valcarce DG, Martínez-Vázquez JM, Martín I, Calderón-García AÁ, Gonzalez-Nunez V, and Robles V
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- Animals, DNA Methylation, Fisheries, Flatfishes, Gene Expression Regulation, Male, MicroRNAs genetics, MicroRNAs metabolism, Proteomics, Dopamine metabolism, Reproduction physiology, Spermatogenesis physiology, Spermatozoa metabolism
- Abstract
Senegalese sole (Solea senegalensis) is a species with a high commercial value that exhibits a reproductive dysfunction in males born and raised in captivity (F1) that hinders their sustainable culture. The present study evaluates the sperm quality and dopaminergic pathway of males born in the wild environment and of F1 males. Traditional sperm analyses were performed, finding only significant differences in curvilinear velocity (VCL) and no significant differences in viability and total motility. No differences in global sperm methylation were observed either in spermatozoa or brain between the two groups (F1 and wild-born males). However, our results point to a different sperm molecular signature between wild fish and fish born in captivity, specifically the differential expression in miR-let7-d and miR-200a-5p between these two groups. miR-let7-d has been correlated with spermatogenesis and sex preferences, whereas the miR-200 family is implied in target innervation of dopaminergic neurons in zebrafish. When we analysed the dopaminergic pathway, no differences were found in terms of different mRNA expression of dopaminergic markers. However, some differences were detected in terms of tyrosine hydroxylase protein expression by western blot analysis, thus suggesting an altered post-transcriptional regulation in F1 males. The results of this study suggest that an altered sperm miRNA signature in F1 males could be one possible mode of transmission of reproductive dysfunction to the progeny. more...
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- 2019
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15. Role of the sugar moiety on the opioid receptor binding and conformation of a series of enkephalin neoglycopeptides.
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Rosa M, Gonzalez-Nunez V, Barreto-Valer K, Marcelo F, Sánchez-Sánchez J, Calle LP, Arévalo JC, Rodríguez RE, Jiménez-Barbero J, Arsequell G, and Valencia G
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- Animals, Glycopeptides chemistry, Glycosylation, Magnetic Resonance Spectroscopy, Male, Mice, Mice, Inbred C57BL, Protein Conformation, Structure-Activity Relationship, Carbohydrates chemistry, Enkephalins chemistry, Glycopeptides metabolism, Receptors, Opioid metabolism
- Abstract
Glycosylation by simple sugars is a drug discovery alternative that has been explored with varying success for enhancing the potency and bioavailability of opioid peptides. Long ago we described two O-glycosides having either β-Glucose and β-Galactose of (d-Met
2 , Pro5 )-enkephalinamide showing one of the highest antinociceptive activities known. Here, we report the resynthesis of these two analogs and the preparation of three novel neoglycopeptide derivatives (α-Mannose, β-Lactose and β-Cellobiose). Binding studies to cloned zebrafish opioid receptors showed very small differences of affinity between the parent compound and the five glycopeptides thus suggesting that the nature of the carbohydrate moiety plays a minor role in determining the binding mode. Indeed, NMR conformational studies, combined with molecular mechanics calculations, indicated that all glycopeptides present the same major conformation either in solution or membrane-like environment. The evidences provided here highlight the relevance for in vivo activity of the conjugating bond between the peptide and sugar moieties in opioid glycopeptides., (Copyright © 2017 Elsevier Ltd. All rights reserved.) more...- Published
- 2017
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16. Role of morphine, miR-212/132 and mu opioid receptor in the regulation of Bdnf in zebrafish embryos.
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Jimenez-Gonzalez A, García-Concejo A, López-Benito S, Gonzalez-Nunez V, Arévalo JC, and Rodriguez RE
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- Animals, Gene Expression Regulation, Developmental, HEK293 Cells, Humans, Receptor, trkB analysis, Brain-Derived Neurotrophic Factor analysis, MicroRNAs physiology, Morphine pharmacology, Receptors, Opioid, mu physiology, Zebrafish embryology
- Abstract
Background: Morphine is one of the first-line therapies for the treatment of pain despite its secondary effects. It modifies the expression of epigenetic factors like miRNAs. In the present study, we analyzed miR-212 and miR-132 and their implication in morphine effects in the zebrafish Central Nervous System (CNS) through the regulation of Bdnf expression., Methods: We used control and knock-down zebrafish embryos to assess the effects of morphine in miRNAs 212/132 and mitotic or apoptotic cells by qPCR, immunohistochemistry and TUNEL assay, respectively. Bdnf and TrkB were studied by western blot and through a primary neuron culture. A luciferase assay was performed to confirm the binding of miRNAs 212/132 to mecp2., Results: Morphine exposure decreases miR-212 but upregulates miR-132, as wells as Bdnf and TrkB, and changes the localization of proliferative cells. However, Bdnf expression was downregulated when miRNAs 212/132 and oprm1 were knocked-down. Furthermore, we proved that these miRNAs inhibit mecp2 expression by binding to its mRNA sequence. The described effects were corroborated in a primary neuron culture from zebrafish embryos., Conclusions: We propose a mechanism in which morphine alters the levels of miRNAs 212/132 increasing Bdnf expression through mecp2 inhibition. oprm1 is also directly involved in this regulation. The present work confirms a relationship between the opioid system and neurotrophins and shows a key role of miR-212 and miR-132 on morphine effects through the regulation of Bdnf pathway., General Significance: miRNAs 212/132 are novel regulators of morphine effects on CNS. Oprm1 controls the normal expression of Bdnf., (Copyright © 2016. Published by Elsevier B.V.) more...
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- 2016
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17. Design, synthesis, pharmacological evaluation and molecular dynamics of β-amino acids morphan-derivatives as novel ligands for opioid receptors.
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Nieto CT, Gonzalez-Nunez V, Rodríguez RE, Diez D, and Garrido NM
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- Dose-Response Relationship, Drug, Humans, Ligands, Molecular Structure, Morphinans chemical synthesis, Receptors, Opioid, mu chemistry, Structure-Activity Relationship, Amino Acids chemistry, Drug Design, Molecular Dynamics Simulation, Morphinans chemistry, Morphinans metabolism, Receptors, Opioid, mu metabolism
- Abstract
Structure-Activity Relationship (SAR) is a current approach in the design of new pharmacological agents. We previously reported the synthesis of a novel analogue of morphine, a 2-azabicyclo[3.3.1]nonane, which contains a β-amino acid. This bicyclic core exhibits two distinctive chemical handles for further elaboration, which allowed us to create a library of morphan-containing compounds by in silico molecular docking on the μ opioid receptor. Lead candidates were synthesized and biological tests were performed to evaluate their ability to bind to opioid receptors. The four top compounds, three phenyl esters and an N-phenylethyl morphan derivative, were selected for Molecular Dynamics simulations to get topological and thermodynamic information. Aromatic morphan derivatives displayed an interacting domain which fits into a hydrophobic cleft and the effect of the substituents in their affinity was explained by the differences in the calculated binding free energies. Our results indicate that the 3D arrangement of the aromatic ring in the morphine derivatives is not a key issue for a specific ligand - μ receptor interaction. Thus, these morphan derivatives represent a new class of opioid receptor ligands which may be of great use in the clinical practice., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.) more...
- Published
- 2015
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18. Role of gabra2 , GABA A receptor alpha-2 subunit, in CNS development.
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Gonzalez-Nunez V
- Abstract
gabra2 gene codes for the alpha-2 subunit of the GABA
A receptor, one of the ionotropic receptors which has been related to anxiety, depression and other behavioural disorders, including drug dependence and schizophrenia. GABAergic signalling also plays a role during development, by promoting neural stem cell maintenance and renewal. To investigate the role of gabra2 in CNS development, gabra2 deficient zebrafish were generated. The pattern of proliferation during the embryonic development was disrupted in morphant embryos, which also displayed an increase in the number of apoptotic nuclei mainly at the mid- and hindbrain regions. The expression of several genes ( notch1, pax2, fgf8 and wnt1 ) known to contribute to the development of the central nervous system was also affected in gabra2 morpholino-injected embryos, although no changes were found for pax6a and shh a expression. The transcriptional activity of neuroD (a proneural gene involved in early neuronal determination) was down-regulated in gabra2 deficient embryos, and the expression pattern of gad1b (GABA-synthesising enzyme GAD67) was clearly reduced in injected fish. I propose that gabra2 might be interacting with those signalling pathways that regulate proliferation, differentiation and neurogenesis during the embryonic development; thus, gabra2 might be playing a role in the differentiation of the mesencephalon and cerebellum. Given that changes in GABAergic circuits during development have been related to several psychiatric disorders, such as autism and schizophrenia, this work might be helpful to understand the role of neurotransmitter systems during CNS development and to assess the developmental effects of several GABAergic drugs. more...- Published
- 2015
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19. Modulation of the Interaction between a Peptide Ligand and a G Protein-Coupled Receptor by Halogen Atoms.
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Rosa M, Caltabiano G, Barreto-Valer K, Gonzalez-Nunez V, Gómez-Tamayo JC, Ardá A, Jiménez-Barbero J, Pardo L, Rodríguez RE, Arsequell G, and Valencia G
- Abstract
Systematic halogenation of two native opioid peptides has shown that halogen atoms can modulate peptide-receptor interactions in different manners. First, halogens may produce a steric hindrance that reduces the binding of the peptide to the receptor. Second, chlorine, bromine, or iodine may improve peptide binding if their positive σ-hole forms a halogen bond interaction with negatively charged atoms of the protein. Lastly, the negative electrostatic potential of fluorine can interact with positively charged atoms of the protein to improve peptide binding. more...
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- 2015
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20. Morphine modulates cell proliferation through mir133b &mir128 in the neuroblastoma SH-SY5Y cell line.
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Gonzalez-Nunez V, Noriega-Prieto JA, and Rodríguez RE
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- Cell Line, Tumor, Humans, Naloxone pharmacology, Neuroblastoma pathology, Cell Proliferation drug effects, MicroRNAs physiology, Morphine pharmacology
- Abstract
Neuroblastoma is a childhood cancer with high incidence and high mortality rate. Great efforts are made to find new treatments and molecular markers for diagnosis and prognosis. miRNAs stand for novel strategies to modulate tumor growth, as they can act either as tumor suppressors or as oncogenes. Morphine is an opioid agonist widely used to treat severe and chronic pain, as for example cancer pain. Previous studies have revealed that morphine is able to modify cancer progression, by acting on proliferation or on apoptosis; however, up to date, the available results are contradictory, maybe due to the different doses used, routes of administration and model systems. While some studies show that morphine promotes cell proliferation and metastasis, other authors sustain that morphine effect is mainly antiproliferative and pro-apoptotic. In this study we aim to establish the effect of chronic opiate administration on cell proliferation in the neuroblastoma SH-SY5Y cell line. Low doses of morphine (10nM) promoted cell proliferation in undifferentiated cells and reduced the expression levels of miR133b, while higher doses (1μM) inhibited cell proliferation and correlated with decreased levels of miR133b and miR128 without triggering apoptosis. Naloxone, the classical opioid antagonist, could not fully block the effect of morphine on miR128 expression, so that the observed effect may be mediated by non-opioid mechanisms. Our results represent a further contribution to the hypothesis that a joint regulation of miRNA networks and the specific characteristics of the target tissue may determine the effect of morphine on tumor cell growth., (Copyright © 2014. Published by Elsevier B.V.) more...
- Published
- 2014
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21. In vivo regulation of the μ opioid receptor: role of the endogenous opioid agents.
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Gonzalez-Nunez V, Jimenez González A, Barreto-Valer K, and Rodríguez RE
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- Analgesics, Opioid metabolism, Animals, Female, HEK293 Cells, Humans, Kidney cytology, Kidney embryology, Morphine metabolism, Opioid Peptides metabolism, Pregnancy, Receptors, Opioid, mu genetics, Zebrafish embryology, Zebrafish genetics, Analgesics, Opioid administration & dosage, Gene Expression Regulation, Kidney metabolism, Morphine administration & dosage, Opioid Peptides administration & dosage, Receptors, Opioid, mu metabolism, Zebrafish metabolism
- Abstract
It is well known that genotypic differences can account for the subject-specific responses to opiate administration. In this regard, the basal activity of the endogenous system (either at the receptor or ligand level) can modulate the effects of exogenous agonists as morphine and vice versa. The μ opioid receptor from zebrafish, dre-oprm1, binds endogenous peptides and morphine with similar affinities. Morphine administration during development altered the expression of the endogenous opioid propeptides proenkephalins and proopiomelanocortin. Treatment with opioid peptides (Met-enkephalin [Met-ENK], Met-enkephalin-Gly-Tyr [MEGY] and β-endorphin [β-END]) modulated dre-oprm1 expression during development. Knocking down the dre-oprm1 gene significantly modified the mRNA expression of the penk and pomc genes, thus indicating that oprm1 is involved in shaping penk and pomc expression. In addition, the absence of a functional oprm1 clearly disrupted the embryonic development, since proliferation was disorganized in the central nervous system of oprm1-morphant embryos: mitotic cells were found widespread through the optic tectum and were not restricted to the proliferative areas of the mid- and hindbrain. Transferase-mediated dUTP nick-end labeling (TUNEL) staining revealed that the number of apoptotic cells in the central nervous system (CNS) of morphants was clearly increased at 24-h postfertilization. These findings clarify the role of the endogenous opioid system in CNS development. Our results will also help unravel the complex feedback loops that modulate opioid activity and that may be involved in establishing a coordinated expression of both receptors and endogenous ligands. Further knowledge of the complex interactions between the opioid system and analgesic drugs will provide insights that may be relevant for analgesic therapy. more...
- Published
- 2013
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22. Synthesis, biological evaluation and structural characterization of novel glycopeptide analogues of nociceptin N/OFQ.
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Arsequell G, Rosa M, Mayato C, Dorta RL, Gonzalez-Nunez V, Barreto-Valer K, Marcelo F, Calle LP, Vázquez JT, Rodríguez RE, Jiménez-Barbero J, and Valencia G
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- Amino Acid Sequence, Animals, Binding, Competitive, Cell Line, Glycopeptides chemical synthesis, Humans, Models, Molecular, Molecular Sequence Data, Opioid Peptides chemical synthesis, Protein Binding, Receptors, Opioid agonists, Zebrafish, Nociceptin, Glycopeptides chemistry, Glycopeptides pharmacology, Opioid Peptides chemistry, Opioid Peptides pharmacology, Receptors, G-Protein-Coupled metabolism
- Abstract
To examine if the biological activity of the N/OFQ peptide, which is the native ligand of the pain-related and viable drug target NOP receptor, could be modulated by glycosylation and if such effects could be conformationally related, we have synthesized three N/OFQ glycopeptide analogues, namely: [Thr(5)-O-α-D-GalNAc-N/OFQ] (glycopeptide 1), [Ser(10)-O-α-D-GalNAc]-N/OFQ (glycopeptide 2) and [Ser(10)-O-β-D-GlcNAc]-N/OFQ] (glycopeptide 3). They were tested for biological activity in competition binding assays using the zebrafish animal model in which glycopeptide 2 exhibited a slightly improved binding affinity, whereas glycopeptide 1 showed a remarkably reduced binding affinity compared to the parent compound and glycopeptide 3. The structural analysis of these glycopeptides and the parent N/OFQ peptide by NMR and circular dichroism indicated that their aqueous solutions are mainly populated by random coil conformers. However, in membrane mimic environments a certain proportion of the molecules of all these peptides exist as α-helix structures. Interestingly, under these experimental conditions, glycopeptide 1 (glycosylated at Thr-5) exhibited a population of folded hairpin-like geometries. From these facts it is tempting to speculate that nociceptin analogues showing linear helical structures are more complementary and thus interact more efficiently with the native NOP receptor than folded structures, since glycopeptide 1 showed a significantly reduced binding affinity for the NOP receptor. more...
- Published
- 2011
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23. Characterization of drCol 15a1b: a novel component of the stem cell niche in the zebrafish retina.
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Gonzalez-Nunez V, Nocco V, and Budd A
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- Animals, Collagen classification, Collagen genetics, Collagen metabolism, Immunohistochemistry, In Situ Hybridization, Phylogeny, Polymerase Chain Reaction, Retina embryology, Zebrafish, Zebrafish Proteins classification, Zebrafish Proteins genetics, Retina metabolism, Stem Cell Niche metabolism, Zebrafish Proteins metabolism
- Abstract
There is a clear need to develop novel tools to help improve our understanding of stem cell biology, and potentially also the utility of stem cells in regenerative medicine. We report the cloning, functional, and bioinformatic characterization of a novel stem cell marker in the zebrafish retina, drCol 15a1b. The expression pattern of drCol 15a1b is restricted to stem cell niches located in the central nervous system, whereas other collagen XVs are associated with muscle and endothelial tissues. Knocking down drCol 15a1b expression causes smaller eyes, ear defects, and brain edema. Microscopic analysis reveals enhanced proliferation in the morphant eye, with many mitotic nuclei located in the central retina, together with a delayed differentiation of the mature retinal cell types. Besides, several markers known to be expressed in the ciliary marginal zone display broader expression areas in morpholino-injected embryos, suggesting an anomalous diffusion of signaling effectors from the sonic hedgehog and notch pathways. These results indicate that drCol 15a1b is a novel stem cell marker in the central nervous system that has a key role in homing stem cells into specialized niches in the adult organism. Moreover, mutations in the hCol 18a1 gene are responsible for the Knobloch syndrome, which affects brain and retinal structures, suggesting that drCol 15a1b may function similarly to mammalian Col 18a1. Thus, our results shed new light on the signaling pathways that underlie the maintenance of stem cells in the adult organism while helping us to understand the role of extracellular matrix proteins in modulating the signals that determine stem cell differentiation, cell cycle exit and apoptosis. more...
- Published
- 2010
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24. Identification of two proopiomelanocortin genes in zebrafish (Danio rerio).
- Author
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Gonzalez-Nunez V, Gonzalez-Sarmiento R, and Rodríguez RE
- Subjects
- Adrenocorticotropic Hormone genetics, Amino Acid Sequence, Animals, Base Sequence, Brain metabolism, Cloning, Molecular, Conserved Sequence, Exons, Introns, Phylogeny, Pituitary Gland metabolism, Pro-Opiomelanocortin biosynthesis, Pro-Opiomelanocortin classification, RNA, Messenger biosynthesis, Reverse Transcriptase Polymerase Chain Reaction methods, Sequence Alignment, Zebrafish, Zebrafish Proteins biosynthesis, alpha-MSH genetics, beta-Endorphin genetics, beta-Lipotropin genetics, Pro-Opiomelanocortin genetics, Zebrafish Proteins genetics
- Abstract
Characterization of a newly cloned proopiomelanocortin (POMC) gene in the teleost zebrafish, Danio rerio, is reported. This gene is formed by three exons and two introns, and its complete cDNA codes for a polypeptide of 222 amino acids. Zebrafish proopiomelanocortin (zfPOMC) contains the consensus sequences for ACTH, gamma-LPH, beta-MSH and beta-endorphin (beta-END). RT-PCR expression studies indicate that zfPOMC is selectively expressed in nervous tissue and in the pituitary gland. An homologous sequence to zfPOMC in the zebrafish genome is also presented. It is possible that this sequence represents part of a duplicate POMC, which might have appeared as a result of an extra genome duplication that have taken place in the cyprinidae family or even in all teleosts. Comparisons between the two zebrafish beta-endorphins and among these peptides and its homologues in other species are also presented. more...
- Published
- 2003
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