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Pesquisa : D02.491.567.249 [Categoria DeCS]
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  1 / 105 MEDLINE  
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[PMID]:27861886
[Au] Autor:Ichihara Y; Doi T; Ryu Y; Nagao M; Sawada Y; Ogata T
[Ad] Endereço:Department of Rehabilitation for Movement Functions, National Rehabilitation Center for Persons With Disabilities, Saitama, Japan.
[Ti] Título:Oligodendrocyte Progenitor Cells Directly Utilize Lactate for Promoting Cell Cycling and Differentiation.
[So] Source:J Cell Physiol;232(5):986-995, 2017 May.
[Is] ISSN:1097-4652
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Oligodendrocyte progenitor cells (OPCs) undergo marked morphological changes to become mature oligodendrocytes, but the metabolic resources for this process have not been fully elucidated. Although lactate, a metabolic derivative of glycogen, has been reported to be consumed in oligodendrocytes as a metabolite, and to ameliorate hypomyelination induced by low glucose conditions, it is not clear about the direct contribution of lactate to cell cycling and differentiation of OPCs, and the source of lactate for remyelination. Therefore, we evaluated the effect of 1,4-dideoxy-1,4-imino-d-arabinitol (DAB), an inhibitor of the glycogen catabolic enzyme glycogen phosphorylase, in a mouse cuprizone model. Cuprizone induced demyelination in the corpus callosum and remyelination occurred after cuprizone treatment ceased. This remyelination was inhibited by the administration of DAB. To further examine whether lactate affects proliferation or differentiation of OPCs, we cultured mouse primary OPC-rich cells and analyzed the effect of lactate. Lactate rescued the slowed cell cycling induced by 0.4 mM glucose, as assessed by the BrdU-positive cell ratio. Lactate also promoted OPC differentiation detected by monitoring the mature oligodendrocyte marker myelin basic protein, in the presence of both 36.6 mM and 0.4 mM glucose. Furthermore, these lactate-mediated effects were suppressed by the reported monocarboxylate transporter inhibitor, α-cyano-4-hydroxy-cinnamate. These results suggest that lactate directly promotes the cell cycling rate and differentiation of OPCs, and that glycogen, one of the sources of lactate, contributes to remyelination in vivo. J. Cell. Physiol. 232: 986-995, 2017. © 2016 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc.
[Mh] Termos MeSH primário: Ciclo Celular
Diferenciação Celular
Ácido Láctico/metabolismo
Oligodendroglia/citologia
Células-Tronco/citologia
[Mh] Termos MeSH secundário: Animais
Arabinose/farmacologia
Ciclo Celular/efeitos dos fármacos
Morte Celular/efeitos dos fármacos
Diferenciação Celular/efeitos dos fármacos
Sobrevivência Celular/efeitos dos fármacos
Células Cultivadas
Corpo Caloso/patologia
Cuprizona
Doenças Desmielinizantes/metabolismo
Doenças Desmielinizantes/patologia
Feminino
Glucose/farmacologia
Imino Furanoses/farmacologia
Ácido Láctico/farmacologia
Masculino
Camundongos Endogâmicos C57BL
Modelos Biológicos
Transportadores de Ácidos Monocarboxílicos/antagonistas & inibidores
Transportadores de Ácidos Monocarboxílicos/metabolismo
Bainha de Mielina/efeitos dos fármacos
Bainha de Mielina/metabolismo
Células-Tronco/efeitos dos fármacos
Células-Tronco/metabolismo
Álcoois Açúcares/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Imino Furanoses); 0 (Monocarboxylic Acid Transporters); 0 (Sugar Alcohols); 100937-53-9 (1,4-dideoxy-1,4-iminoarabinitol); 33X04XA5AT (Lactic Acid); 5N16U7E0AO (Cuprizone); B40ROO395Z (Arabinose); IY9XDZ35W2 (Glucose)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170508
[Lr] Data última revisão:
170508
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161119
[St] Status:MEDLINE
[do] DOI:10.1002/jcp.25690


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[PMID]:27565616
[Au] Autor:Miyauchi R; Ono C; Ohnuki T; Shiba Y
[Ad] Endereço:Modality Research Laboratories, R&D Division, Daiichi Sankyo Co., Ltd., Tokyo, Japan miyauchi.ryuki.d4@daiichisankyo.co.jp.
[Ti] Título:Nectrisine Biosynthesis Genes in Thelonectria discophora SANK 18292: Identification and Functional Analysis.
[So] Source:Appl Environ Microbiol;82(21):6414-6422, 2016 Nov 01.
[Is] ISSN:1098-5336
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The fungus Thelonectria discophora SANK 18292 produces the iminosugar nectrisine, which has a nitrogen-containing heterocyclic 5-membered ring and acts as a glycosidase inhibitor. In our previous study, an oxidase (designated NecC) that converts 4-amino-4-deoxyarabinitol to nectrisine was purified from T. discophora cultures. However, the genes required for nectrisine biosynthesis remained unclear. In this study, the nectrisine biosynthetic gene cluster in T. discophora was identified from the contiguous genome sequence around the necC gene. Gene disruption and complementation studies and heterologous expression of the gene showed that necA, necB, and necC could be involved in nectrisine biosynthesis, during which amination, dephosphorylation, and oxidation occur. It was also demonstrated that nectrisine could be produced by recombinant Escherichia coli coexpressing the necA, necB, and necC genes. These findings provide the foundation to develop a bacterial production system for nectrisine or its intermediates through genetic engineering. IMPORTANCE: Iminosugars might have great therapeutic potential for treatment of many diseases. However, information on the genes for their biosynthesis is limited. In this study, we report the identification of genes required for biosynthesis of the iminosugar nectrisine in Thelonectria discophora SANK 18292, which was verified by disruption, complementation, and heterologous expression of the genes involved. We also demonstrate heterologous production of nectrisine by recombinant E. coli, toward developing an efficient production system for nectrisine or its intermediates through genetic engineering.
[Mh] Termos MeSH primário: Genes Fúngicos
Hypocreales/genética
Imino Furanoses/isolamento & purificação
Imino Furanoses/metabolismo
[Mh] Termos MeSH secundário: Aminação
Escherichia coli/genética
Teste de Complementação Genética
Engenharia Genética
Genoma Fúngico
Hypocreales/metabolismo
Imino Furanoses/química
Família Multigênica
Oxirredução
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Imino Furanoses); 108692-47-3 (nectrisine)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171027
[Lr] Data última revisão:
171027
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160828
[St] Status:MEDLINE


  3 / 105 MEDLINE  
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[PMID]:27019223
[Au] Autor:Namanja-Magliano HA; Stratton CF; Schramm VL
[Ad] Endereço:Department of Biochemistry, Albert Einstein College of Medicine , 1300 Morris Park Avenue, Bronx, New York 10461, United States.
[Ti] Título:Transition State Structure and Inhibition of Rv0091, a 5'-Deoxyadenosine/5'-methylthioadenosine Nucleosidase from Mycobacterium tuberculosis.
[So] Source:ACS Chem Biol;11(6):1669-76, 2016 06 17.
[Is] ISSN:1554-8937
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:5'-Methylthioadenosine/S-adenosylhomocysteine nucleosidase (MTAN) is a bacterial enzyme that catalyzes the hydrolysis of the N-ribosidic bond in 5'-methylthioadenosine (MTA) and S-adenosylhomocysteine (SAH). MTAN activity has been linked to quorum sensing pathways, polyamine biosynthesis, and adenine salvage. Previously, the coding sequence of Rv0091 was annotated as a putative MTAN in Mycobacterium tuberculosis. Rv0091 was expressed in Escherichia coli, purified to homogeneity, and shown to be a homodimer, consistent with MTANs from other microorganisms. Substrate specificity for Rv0091 gave a preference for 5'-deoxyadenosine relative to MTA or SAH. Intrinsic kinetic isotope effects (KIEs) for the hydrolysis of [1'-(3)H], [1'-(14)C], [5'-(3)H2], [9-(15)N], and [7-(15)N]MTA were determined to be 1.207, 1.038, 0.998, 1.021, and 0.998, respectively. A model for the transition state structure of Rv0091 was determined by matching KIE values predicted via quantum chemical calculations to the intrinsic KIEs. The transition state shows a substantial loss of C1'-N9 bond order, well-developed oxocarbenium character of the ribosyl ring, and weak participation of the water nucleophile. Electrostatic potential surface maps for the Rv0091 transition state structure show similarity to DADMe-immucillin transition state analogues. DADMe-immucillin transition state analogues showed strong inhibition of Rv0091, with the most potent inhibitor (5'-hexylthio-DADMe-immucillinA) displaying a Ki value of 87 pM.
[Mh] Termos MeSH primário: Adenosina/análogos & derivados
Adenosina/química
Imino Furanoses/química
Mycobacterium tuberculosis/enzimologia
Purina-Núcleosídeo Fosforilase/antagonistas & inibidores
Pirimidinonas/química
Pirrolidinas/química
[Mh] Termos MeSH secundário: Desoxiadenosinas/química
Purina-Núcleosídeo Fosforilase/química
Teoria Quântica
S-Adenosil-Homocisteína/química
Tionucleosídeos/química
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (5'-hexylthio-DADMe-immucillin A); 0 (Deoxyadenosines); 0 (Imino Furanoses); 0 (Pyrimidinones); 0 (Pyrrolidines); 0 (Thionucleosides); 4754-39-6 (5'-deoxyadenosine); 634Z2VK3UQ (5'-methylthioadenosine); 979-92-0 (S-Adenosylhomocysteine); EC 2.4.2.1 (Purine-Nucleoside Phosphorylase); EC 2.4.2.28 (5'-methylthioadenosine phosphorylase); K72T3FS567 (Adenosine)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170919
[Lr] Data última revisão:
170919
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160329
[St] Status:MEDLINE
[do] DOI:10.1021/acschembio.6b00144


  4 / 105 MEDLINE  
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[PMID]:26790356
[Au] Autor:Li YX; Kinami K; Hirokami Y; Kato A; Su JK; Jia YM; Fleet GW; Yu CY
[Ad] Endereço:Beijing National Laboratory for Molecular Science (BNLMS), CAS Key Laboratory of Molecular Recognition and Function, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China. yucy@iccas.ac.cn.
[Ti] Título:Gem-difluoromethylated and trifluoromethylated derivatives of DMDP-related iminosugars: synthesis and glycosidase inhibition.
[So] Source:Org Biomol Chem;14(7):2249-63, 2016 Feb 21.
[Is] ISSN:1477-0539
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Gem-difluoromethylated and trifluoromethylated derivatives of DMDP-related iminosugars have been synthesized from cyclic nitrones 12, 13, 18, ent-18 or 23 and nitrone-derived aldehydes 20 or ent-20. The fluorinated iminosugars were assayed against various glycosidases, and ent-8 showed moderate but selective α-l-rhamnosidase inhibition. Difluoro or trifluoro units influenced the inhibitory activities of iminosugars in a more complex manner than single fluoro substitution. This may be correlated with their highly hydrophobic character and strong electron-withdrawing effect.
[Mh] Termos MeSH primário: Clorofluorcarbonetos de Metano/química
Glicosídeo Hidrolases/antagonistas & inibidores
Hidrocarbonetos Fluorados/química
Imino Furanoses/química
Óxidos de Nitrogênio/química
[Mh] Termos MeSH secundário: Clorofluorcarbonetos de Metano/síntese química
Ciclização
Hidrocarbonetos Fluorados/síntese química
Imino Furanoses/síntese química
Estrutura Molecular
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Chlorofluorocarbons, Methane); 0 (Hydrocarbons, Fluorinated); 0 (Imino Furanoses); 0 (Nitrogen Oxides); 0 (nitrones); 77JW9K722X (difluoromethane); EC 3.2.1.- (Glycoside Hydrolases); ZJ51L9A260 (fluoroform)
[Em] Mês de entrada:1612
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160122
[St] Status:MEDLINE
[do] DOI:10.1039/c5ob02474a


  5 / 105 MEDLINE  
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[PMID]:26706033
[Au] Autor:Liu C; Hou L; Meng A; Han G; Zhang W; Jiang S
[Ad] Endereço:School of Pharmacy, North China University of Science and Technology, Tangshan 063000, China. Electronic address: chunyanliu@ncst.edu.cn.
[Ti] Título:Design, synthesis and bioactivity evaluation of Galf mimics as antitubercular agents.
[So] Source:Carbohydr Res;429:135-42, 2016 Jun 24.
[Is] ISSN:1873-426X
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:A series of novel Galf mimics has been synthesized and characterized by IR, (1)H NMR, (13)C NMR, mass spectral and element analysis. All the newly prepared compounds were screened for their antitubercular activities. Bioactivity assays manifested that most of Galf mimics exhibited good antitubercular activities. Especially compound 4d and 4e displayed remarkable antitubercular efficacies, which were comparable to ethambutol.
[Mh] Termos MeSH primário: Antituberculosos/síntese química
Parede Celular/efeitos dos fármacos
Desenho de Drogas
Glicoconjugados/antagonistas & inibidores
Mycobacterium tuberculosis/efeitos dos fármacos
[Mh] Termos MeSH secundário: Antituberculosos/farmacologia
Parede Celular/metabolismo
Etambutol/farmacologia
Proteínas Fúngicas/genética
Proteínas Fúngicas/metabolismo
Galactose/análogos & derivados
Galactose/química
Galactose/genética
Galactose/metabolismo
Expressão Gênica
Glicoconjugados/química
Imino Furanoses/química
Transferases Intramoleculares/genética
Transferases Intramoleculares/metabolismo
Testes de Sensibilidade Microbiana
Mimetismo Molecular
Mycobacterium tuberculosis/genética
Mycobacterium tuberculosis/metabolismo
Transferases/genética
Transferases/metabolismo
Difosfato de Uridina/análogos & derivados
Difosfato de Uridina/química
Difosfato de Uridina/genética
Difosfato de Uridina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antitubercular Agents); 0 (Fungal Proteins); 0 (Glycoconjugates); 0 (Imino Furanoses); 0 (uridine diphosphate galactofuranose); 58-98-0 (Uridine Diphosphate); 8G167061QZ (Ethambutol); EC 2.- (Transferases); EC 5.4.- (Intramolecular Transferases); EC 5.4.99.9 (UDP-galactopyranose mutase); X2RN3Q8DNE (Galactose)
[Em] Mês de entrada:1701
[Cu] Atualização por classe:170119
[Lr] Data última revisão:
170119
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151227
[St] Status:MEDLINE


  6 / 105 MEDLINE  
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[PMID]:26646452
[Au] Autor:Kashyap MK; Kumar D; Jones H; Amaya-Chanaga CI; Choi MY; Melo-Cardenas J; Ale-Ali A; Kuhne MR; Sabbatini P; Cohen LJ; Shelat SG; Rassenti LZ; Kipps TJ; Cardarelli PM; Castro JE
[Ad] Endereço:UCSD-Moores Cancer Center, La Jolla, CA, USA.
[Ti] Título:Ulocuplumab (BMS-936564 / MDX1338): a fully human anti-CXCR4 antibody induces cell death in chronic lymphocytic leukemia mediated through a reactive oxygen species-dependent pathway.
[So] Source:Oncotarget;7(3):2809-22, 2016 Jan 19.
[Is] ISSN:1949-2553
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The CXCR4 receptor (Chemokine C-X-C motif receptor 4) is highly expressed in different hematological malignancies including chronic lymphocytic leukemia (CLL). The CXCR4 ligand (CXCL12) stimulates CXCR4 promoting cell survival and proliferation, and may contribute to the tropism of leukemia cells towards lymphoid tissues. Therefore, strategies targeting CXCR4 may constitute an effective therapeutic approach for CLL. To address that question, we studied the effect of Ulocuplumab (BMS-936564), a fully human IgG4 anti-CXCR4 antibody, using a stroma--CLL cells co-culture model. We found that Ulocuplumab (BMS-936564) inhibited CXCL12 mediated CXCR4 activation-migration of CLL cells at nanomolar concentrations. This effect was comparable to AMD3100 (Plerixafor--Mozobil), a small molecule CXCR4 inhibitor. However, Ulocuplumab (BMS-936564) but not AMD3100 induced apoptosis in CLL at nanomolar concentrations in the presence or absence of stromal cell support. This pro-apoptotic effect was independent of CLL high-risk prognostic markers, was associated with production of reactive oxygen species and did not require caspase activation. Overall, these findings are evidence that Ulocuplumab (BMS-936564) has biological activity in CLL, highlight the relevance of the CXCR4-CXCL12 pathway as a therapeutic target in CLL, and provide biological rationale for ongoing clinical trials in CLL and other hematological malignancies.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Apoptose/efeitos dos fármacos
Quimiocina CXCL12/biossíntese
Imino Furanoses/farmacologia
Leucemia Linfocítica Crônica de Células B/tratamento farmacológico
Pirimidinonas/farmacologia
Espécies Reativas de Oxigênio/metabolismo
Receptores CXCR4/antagonistas & inibidores
[Mh] Termos MeSH secundário: Actinas/metabolismo
Movimento Celular/efeitos dos fármacos
Proliferação Celular
Sobrevivência Celular
Quimiocina CXCL12/metabolismo
Ativação Enzimática/efeitos dos fármacos
Compostos Heterocíclicos/farmacologia
Seres Humanos
Células Jurkat
Leucócitos Mononucleares
Receptores CXCR4/biossíntese
Células Tumorais Cultivadas
Proteína Supressora de Tumor p53/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Actins); 0 (Antineoplastic Agents); 0 (CXCL12 protein, human); 0 (CXCR4 protein, human); 0 (Chemokine CXCL12); 0 (Heterocyclic Compounds); 0 (Imino Furanoses); 0 (Pyrimidinones); 0 (Reactive Oxygen Species); 0 (Receptors, CXCR4); 0 (TP53 protein, human); 0 (Tumor Suppressor Protein p53); 155148-31-5 (JM 3100); JNG8L9460Y (ulodesine)
[Em] Mês de entrada:1611
[Cu] Atualização por classe:161230
[Lr] Data última revisão:
161230
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151210
[St] Status:MEDLINE
[do] DOI:10.18632/oncotarget.6465


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[PMID]:26537532
[Au] Autor:Stockwell J; Daniels AD; Windle CL; Harman TA; Woodhall T; Lebl T; Trinh CH; Mulholland K; Pearson AR; Berry A; Nelson A
[Ad] Endereço:School of Chemistry, University of Leeds, Leeds, LS2 9JT, UK. a.s.nelson@leeds.ac.uk.
[Ti] Título:Evaluation of fluoropyruvate as nucleophile in reactions catalysed by N-acetyl neuraminic acid lyase variants: scope, limitations and stereoselectivity.
[So] Source:Org Biomol Chem;14(1):105-12, 2016 Jan 07.
[Is] ISSN:1477-0539
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The catalysis of reactions involving fluoropyruvate as donor by N-acetyl neuraminic acid lyase (NAL) variants was investigated. Under kinetic control, the wild-type enzyme catalysed the reaction between fluoropyruvate and N-acetyl mannosamine to give a 90 : 10 ratio of the (3R,4R)- and (3S,4R)-configured products; after extended reaction times, equilibration occurred to give a 30 : 70 mixture of these products. The efficiency and stereoselectivity of reactions of a range of substrates catalysed by the E192N, E192N/T167V/S208V and E192N/T167G NAL variants were also studied. Using fluoropyruvate and (2R,3S)- or (2S,3R)-2,3-dihydroxy-4-oxo-N,N-dipropylbutanamide as substrates, it was possible to obtain three of the four possible diastereomeric products; for each product, the ratio of anomeric and pyranose/furanose forms was determined. The crystal structure of S. aureus NAL in complex with fluoropyruvate was determined, assisting rationalisation of the stereochemical outcome of C-C bond formation.
[Mh] Termos MeSH primário: Biocatálise
Imino Furanoses/metabolismo
Imino Piranoses/metabolismo
Oxo-Ácido-Liases/metabolismo
Piruvatos/metabolismo
[Mh] Termos MeSH secundário: Imino Furanoses/química
Imino Piranoses/química
Conformação Molecular
Piruvatos/química
Estereoisomerismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Imino Furanoses); 0 (Imino Pyranoses); 0 (Pyruvates); 0 (fluoropyruvate); EC 4.1.3.- (Oxo-Acid-Lyases); EC 4.1.3.3 (N-acetylneuraminate lyase)
[Em] Mês de entrada:1609
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151106
[St] Status:MEDLINE
[do] DOI:10.1039/c5ob02037a


  8 / 105 MEDLINE  
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[PMID]:26503760
[Au] Autor:Boury-Jamot B; Carrard A; Martin JL; Halfon O; Magistretti PJ; Boutrel B
[Ad] Endereço:Centre for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital, Lausanne, Switzerland.
[Ti] Título:Disrupting astrocyte-neuron lactate transfer persistently reduces conditioned responses to cocaine.
[So] Source:Mol Psychiatry;21(8):1070-6, 2016 Aug.
[Is] ISSN:1476-5578
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:A central problem in the treatment of drug addiction is the high risk of relapse often precipitated by drug-associated cues. The transfer of glycogen-derived lactate from astrocytes to neurons is required for long-term memory. Whereas blockade of drug memory reconsolidation represents a potential therapeutic strategy, the role of astrocyte-neuron lactate transport in long-term conditioning has received little attention. By infusing an inhibitor of glycogen phosphorylase into the basolateral amygdala of rats, we report that disruption of astrocyte-derived lactate not only transiently impaired the acquisition of a cocaine-induced conditioned place preference but also persistently disrupted an established conditioning. The drug memory was rescued by L-Lactate co-administration through a mechanism requiring the synaptic plasticity-related transcription factor Zif268 and extracellular signal-regulated kinase (ERK) signalling pathway but not the brain-derived neurotrophic factor (Bdnf). The long-term amnesia induced by glycogenolysis inhibition and the concomitant decreased expression of phospho-ERK were both restored with L-Lactate co-administration. These findings reveal a critical role for astrocyte-derived lactate in positive memory formation and highlight a novel amygdala-dependent reconsolidation process, whose disruption may offer a novel therapeutic target to reduce the long-lasting conditioned responses to cocaine.
[Mh] Termos MeSH primário: Astrócitos/metabolismo
Transtornos Relacionados ao Uso de Cocaína/fisiopatologia
Ácido Láctico/metabolismo
[Mh] Termos MeSH secundário: Tonsila do Cerebelo/metabolismo
Animais
Arabinose
Fator Neurotrófico Derivado do Encéfalo/metabolismo
Proteínas de Transporte/metabolismo
Cocaína/farmacologia
Transtornos Relacionados ao Uso de Cocaína/psicologia
Condicionamento (Psicologia)
Condicionamento Clássico/efeitos dos fármacos
Sinais (Psicologia)
MAP Quinases Reguladas por Sinal Extracelular/metabolismo
Imino Furanoses
Masculino
Proteínas de Membrana/metabolismo
Memória/fisiologia
Neurônios/metabolismo
Ratos
Ratos Sprague-Dawley
Álcoois Açúcares
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Brain-Derived Neurotrophic Factor); 0 (Carrier Proteins); 0 (Imino Furanoses); 0 (Itmap1 protein, rat); 0 (Membrane Proteins); 0 (Sugar Alcohols); 100937-53-9 (1,4-dideoxy-1,4-iminoarabinitol); 33X04XA5AT (Lactic Acid); B40ROO395Z (Arabinose); EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases); I5Y540LHVR (Cocaine)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170925
[Lr] Data última revisão:
170925
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151028
[St] Status:MEDLINE
[do] DOI:10.1038/mp.2015.157


  9 / 105 MEDLINE  
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[PMID]:26293178
[Au] Autor:Zhang Y; Xue Y; Meng S; Luo Y; Liang J; Li J; Ai S; Sun C; Shen H; Zhu W; Wu P; Lu L; Shi J
[Ad] Endereço:National Institute on Drug Dependence and Beijing Key Laboratory on Drug Dependence Research, Beijing, China.
[Ti] Título:Inhibition of Lactate Transport Erases Drug Memory and Prevents Drug Relapse.
[So] Source:Biol Psychiatry;79(11):928-39, 2016 Jun 01.
[Is] ISSN:1873-2402
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Drug memories that associate drug-paired stimuli with the effects of abused drugs contribute to relapse. Exposure to drug-associated contexts causes consolidated drug memories to be in a labile state, during which manipulations can be given to impair drug memories. Although substantial evidence demonstrates the crucial role of neuronal signaling in addiction, little is known about the contribution of astrocyte-neuron communication. METHODS: Rats were trained for cocaine-induced conditioned place preference (CPP) or self-administration and microinjected with the glycogen phosphorylation inhibitor 1,4-dideoxy-1,4-imino-D-arabinitol into the basolateral amygdala (BLA) immediately after retrieval. The concentration of lactate was measured immediately after retrieval via microdialysis, and the CPP score and number of nosepokes were recorded 24 hours later. Furthermore, we used antisense oligodeoxynucleotides to disrupt the expression of astrocytic lactate transporters (monocarboxylate transporters 1 and 2) in the BLA after retrieval, tested the expression of CPP 1 day later, and injected L-lactate into the BLA 15 minutes before retrieval to rescue the effects of the oligodeoxynucleotides. RESULTS: Injection of 1,4-dideoxy-1,4-imino-D-arabinitol into the BLA immediately after retrieval prevented the subsequent expression of cocaine-induced CPP, decreased the concentration of lactate in the BLA, and reduced the number of nosepokes for cocaine self-administration. Disrupting the expression of monocarboxylate transporters 1 and 2 in the BLA also caused subsequent deficits in the expression of cocaine-induced CPP, which was rescued by pretreatment with L-lactate. CONCLUSIONS: Our results suggest that astrocyte-neuron lactate transport in the BLA is critical for the reconsolidation of cocaine memory.
[Mh] Termos MeSH primário: Arabinose/farmacologia
Transtornos Relacionados ao Uso de Cocaína/tratamento farmacológico
Transtornos Relacionados ao Uso de Cocaína/psicologia
Imino Furanoses/farmacologia
Ácido Láctico/metabolismo
Consolidação da Memória/efeitos dos fármacos
Psicotrópicos/farmacologia
Álcoois Açúcares/farmacologia
[Mh] Termos MeSH secundário: Animais
Complexo Nuclear Basolateral da Amígdala/efeitos dos fármacos
Complexo Nuclear Basolateral da Amígdala/metabolismo
Cocaína/administração & dosagem
Transtornos Relacionados ao Uso de Cocaína/metabolismo
Condicionamento (Psicologia)/efeitos dos fármacos
Condicionamento (Psicologia)/fisiologia
Inibidores da Captação de Dopamina/administração & dosagem
Comportamento de Procura de Droga/efeitos dos fármacos
Comportamento de Procura de Droga/fisiologia
Masculino
Consolidação da Memória/fisiologia
Transportadores de Ácidos Monocarboxílicos/antagonistas & inibidores
Transportadores de Ácidos Monocarboxílicos/metabolismo
Ratos Sprague-Dawley
Recidiva
Prevenção Secundária
Autoadministração
Percepção Espacial/efeitos dos fármacos
Percepção Espacial/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Dopamine Uptake Inhibitors); 0 (Imino Furanoses); 0 (Monocarboxylic Acid Transporters); 0 (Psychotropic Drugs); 0 (Sugar Alcohols); 100937-53-9 (1,4-dideoxy-1,4-iminoarabinitol); 33X04XA5AT (Lactic Acid); B40ROO395Z (Arabinose); I5Y540LHVR (Cocaine)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170501
[Lr] Data última revisão:
170501
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150822
[St] Status:MEDLINE


  10 / 105 MEDLINE  
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[PMID]:25865736
[Au] Autor:Miyauchi R; Takatsu T; Suzuki T; Ono Y; Shiba Y
[Ad] Endereço:New Modality Research Laboratories, R&D Division, Daiichi Sankyo Co., Ltd., 1-2-58, Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan. Electronic address: miyauchi.ryuki.d4@daiichisankyo.co.jp.
[Ti] Título:Biosynthesis of nectrisine in Thelonectria discophora SANK 18292.
[So] Source:Phytochemistry;116:87-93, 2015 Aug.
[Is] ISSN:1873-3700
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Nectrisine, an iminosugar with a heterocyclic nitrogen-containing 5-membered ring, acts as a glycosidase inhibitor. Thelonectria discophora SANK 18292, a fungus, was identified as a nectrisine producer from its microbial library in our screening for nectrisine producing microorganisms. Biosynthesis of nectrisine produced by the fungus was studied using stable isotope tracer techniques. Incorporation of (13)C-labeled d-ribose and d-xylose into nectrisine was confirmed by mass spectrometry and (13)C NMR spectroscopy, which suggested that these were its precursors. Chromatographic separation of the hot water extract from the culture broth afforded not only nectrisine, but also substantial amounts of 4-amino-4-deoxyarabinitol. Incubation of the latter with the crude enzyme of the fungus at room temp. caused an increase in levels of nectrisine together with a decrease in amounts of the administered potential precursor suggesting that it is a biosynthetic intermediate. From these results, a biosynthetic pathway to nectrisine is proposed via d-xylulose 5-phosphate and 4-amino-4-deoxyarabinitol by the pentose phosphate pathway.
[Mh] Termos MeSH primário: Hypocreales/química
Imino Furanoses/metabolismo
[Mh] Termos MeSH secundário: Glicosídeo Hidrolases/antagonistas & inibidores
Imino Furanoses/química
Ressonância Magnética Nuclear Biomolecular
Pentosefosfatos/química
Ribose/química
Estereoisomerismo
Álcoois Açúcares/química
Álcoois Açúcares/metabolismo
Tropanos/química
Tropanos/metabolismo
Xilose/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (3-tigloyloxy-6,7-epoxytropane); 0 (4-amino-4-deoxyarabinitol); 0 (Imino Furanoses); 0 (Pentosephosphates); 0 (Sugar Alcohols); 0 (Tropanes); 108692-47-3 (nectrisine); 60802-29-1 (xylulose-5-phosphate); 681HV46001 (Ribose); A1TA934AKO (Xylose); EC 3.2.1.- (Glycoside Hydrolases)
[Em] Mês de entrada:1602
[Cu] Atualização por classe:170815
[Lr] Data última revisão:
170815
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150414
[St] Status:MEDLINE



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