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[PMID]:29348617
[Au] Autor:Miranda AM; Lasiecka ZM; Xu Y; Neufeld J; Shahriar S; Simoes S; Chan RB; Oliveira TG; Small SA; Di Paolo G
[Ad] Endereço:Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, 10032, USA.
[Ti] Título:Neuronal lysosomal dysfunction releases exosomes harboring APP C-terminal fragments and unique lipid signatures.
[So] Source:Nat Commun;9(1):291, 2018 01 18.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Defects in endolysosomal and autophagic functions are increasingly viewed as key pathological features of neurodegenerative disorders. A master regulator of these functions is phosphatidylinositol-3-phosphate (PI3P), a phospholipid synthesized primarily by class III PI 3-kinase Vps34. Here we report that disruption of neuronal Vps34 function in vitro and in vivo impairs autophagy, lysosomal degradation as well as lipid metabolism, causing endolysosomal membrane damage. PI3P deficiency also promotes secretion of unique exosomes enriched for undigested lysosomal substrates, including amyloid precursor protein C-terminal fragments (APP-CTFs), specific sphingolipids, and the phospholipid bis(monoacylglycero)phosphate (BMP), which normally resides in the internal vesicles of endolysosomes. Secretion of these exosomes requires neutral sphingomyelinase 2 and sphingolipid synthesis. Our results reveal a homeostatic response counteracting lysosomal dysfunction via secretion of atypical exosomes eliminating lysosomal waste and define exosomal APP-CTFs and BMP as candidate biomarkers for endolysosomal dysfunction associated with neurodegenerative disorders.
[Mh] Termos MeSH primário: Precursor de Proteína beta-Amiloide/metabolismo
Exossomos/metabolismo
Lipídeos/análise
Lisossomos/metabolismo
Neurônios/metabolismo
[Mh] Termos MeSH secundário: Precursor de Proteína beta-Amiloide/química
Animais
Autofagia/genética
Biomarcadores/metabolismo
Linhagem Celular Tumoral
Classe III de Fosfatidilinositol 3-Quinases/genética
Classe III de Fosfatidilinositol 3-Quinases/metabolismo
Células HEK293
Seres Humanos
Lisofosfolipídeos/metabolismo
Camundongos Endogâmicos C57BL
Camundongos Knockout
Monoglicerídeos/metabolismo
Doenças Neurodegenerativas/diagnóstico
Doenças Neurodegenerativas/metabolismo
Fragmentos de Peptídeos/metabolismo
Fosfatos de Fosfatidilinositol/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 (Amyloid beta-Protein Precursor); 0 (Biomarkers); 0 (Lipids); 0 (Lysophospholipids); 0 (Monoglycerides); 0 (Peptide Fragments); 0 (Phosphatidylinositol Phosphates); 0 (bis(monoacylglyceryl)phosphate); 0 (phosphatidylinositol 3-phosphate); EC 2.7.1.137 (Class III Phosphatidylinositol 3-Kinases)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180306
[Lr] Data última revisão:
180306
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180120
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-02533-w


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[PMID]:29061780
[Au] Autor:Morin C; Fortin S
[Ad] Endereço:SCF Pharma, Ste-Luce, QC, Canada.
[Ti] Título:Docosahexaenoic Acid Monoglyceride Increases Carboplatin Activity in Lung Cancer Models by Targeting EGFR.
[So] Source:Anticancer Res;37(11):6015-6023, 2017 11.
[Is] ISSN:1791-7530
[Cp] País de publicação:Greece
[La] Idioma:eng
[Ab] Resumo:BACKGROUND/AIM: Omega 3 polyunsaturated fatty acids (PUFAs) have been shown to inhibit the induction and progression of many tumor types. The aim of this study was to determine the anticancer effect of docosahexaenoic acid monoglyceride (MAG-DHA) alone and in combination with the chemotherapeutic agent carboplatin (CBT) on lung cancer models. MATERIALS AND METHODS: Adenocarcinoma cell lines A549 and H1299 were used to evaluate the effect of combined MAG-DHA and CBT treatments both in vitro and in vivo in xenograft models. RESULTS: MAG-DHA+CBT treatment decreased cell proliferation and invasion abilities of A549 and H1299 cells. Furthermore, MAG-DHA+CBT treatment resulted in a decreased activation of epithelial growth factor receptor (EGFR) and its downstream extracellular signal-regulated kinase (ERK) in cell lysates. In A549 and H1299 xenograft mouse models, MAG-DHA+CBT treatment reduced tumor growth. CONCLUSION: Combined MAG-DHA and CBT treatment inhibited tumor growth by suppressing EGFR and ERK signaling pathways in lung carcinoma cells.
[Mh] Termos MeSH primário: Carboplatina/farmacologia
Sinergismo Farmacológico
Neoplasias Pulmonares/tratamento farmacológico
Terapia de Alvo Molecular
Monoglicerídeos/farmacologia
Receptor do Fator de Crescimento Epidérmico/antagonistas & inibidores
[Mh] Termos MeSH secundário: Animais
Antineoplásicos/farmacologia
Apoptose/efeitos dos fármacos
Movimento Celular/efeitos dos fármacos
Proliferação Celular/efeitos dos fármacos
Seres Humanos
Neoplasias Pulmonares/metabolismo
Neoplasias Pulmonares/patologia
Camundongos
Camundongos Nus
Células Tumorais Cultivadas
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Monoglycerides); 0 (docosahexaenoic acid monoacylglyceride); BG3F62OND5 (Carboplatin); EC 2.7.10.1 (EGFR protein, human); EC 2.7.10.1 (Receptor, Epidermal Growth Factor)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171031
[Lr] Data última revisão:
171031
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171025
[St] Status:MEDLINE


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[PMID]:28671839
[Au] Autor:Ikegawa C; Ogita A; Doi T; Kumazawa F; Fujita KI; Tanaka T
[Ti] Título:Involvement of Irreversible Vacuolar Membrane Fragmentation in the Lethality of Food Emulsifier Diglycerol Monolaurate against Budding Yeast.
[So] Source:J Agric Food Chem;65(28):5650-5656, 2017 Jul 19.
[Is] ISSN:1520-5118
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Diglycerol monolaurate (DGL) has been manufactured as a novel type of food emulsifier and is being considered for further application as a food preservative. DGL lethality was thus examined against Saccharomyces cerevisiae as a model of a yeast that causes food spoilage. In spite of its molecular structure as a nonionic surfactant, DGL could exhibit lethality at a concentration lower than that which caused disruptive damage to the yeast plasma membrane. DGL lethality was rather accompanied by a dynamic intracellular event such as a marked vacuolar membrane fragmentation. In DGL-treated cells, the tiny dots or particles of fragmented vacuolar membranes failed to fuse into the original large rounded architecture after its removal from medium, which were distinguished from those generated as a result of vacuolar fission normally accelerated under hyperosmotic conditions. Such an irreversible structural damage of the organelle membrane was considered a cause of DGL lethality.
[Mh] Termos MeSH primário: Emulsificantes/farmacologia
Membranas Intracelulares/efeitos dos fármacos
Lauratos/farmacologia
Monoglicerídeos/farmacologia
Saccharomyces cerevisiae/efeitos dos fármacos
Vacúolos/efeitos dos fármacos
[Mh] Termos MeSH secundário: Membranas Intracelulares/metabolismo
Saccharomyces cerevisiae/crescimento & desenvolvimento
Saccharomyces cerevisiae/metabolismo
Vacúolos/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Emulsifying Agents); 0 (Laurates); 0 (Monoglycerides); 27215-38-9 (monolaurin)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170728
[Lr] Data última revisão:
170728
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170704
[St] Status:MEDLINE
[do] DOI:10.1021/acs.jafc.7b01580


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[PMID]:28608752
[Au] Autor:Kikugawa M; Ida T; Ihara H; Sakamoto T
[Ad] Endereço:a Division of Applied Life Sciences, Graduate School of Life and Environmental Sciences , Osaka Prefecture University , Sakai , Japan.
[Ti] Título:Ferulic acid and its water-soluble derivatives inhibit nitric oxide production and inducible nitric oxide synthase expression in rat primary astrocytes.
[So] Source:Biosci Biotechnol Biochem;81(8):1607-1611, 2017 Aug.
[Is] ISSN:1347-6947
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:We recently reported that two water-soluble derivatives of ferulic acid (1-feruloyl glycerol, 1-feruloyl diglycerol) previously developed by our group exhibited protective effects against amyloid-ß-induced neurodegeneration in vitro and in vivo. In the current study, we aimed to further understand this process by examining the derivatives' ability to suppress abnormal activation of astrocytes, the key event of neurodegeneration. We investigated the effects of ferulic acid (FA) derivatives on nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression in rat primary astrocytes. The results showed that these compounds inhibited NO production and iNOS expression in a concentration-dependent manner and that the mechanism underlying these effects was the suppression of the nuclear factor-κB pathway. This evidence suggests that FA and its derivatives may be effective neuroprotective agents and could be useful in the treatment of neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease.
[Mh] Termos MeSH primário: Astrócitos/efeitos dos fármacos
Ácidos Cumáricos/farmacologia
Monoglicerídeos/farmacologia
NF-kappa B/antagonistas & inibidores
Fármacos Neuroprotetores/farmacologia
Óxido Nítrico Sintase Tipo II/antagonistas & inibidores
Óxido Nítrico/antagonistas & inibidores
[Mh] Termos MeSH secundário: Peptídeos beta-Amiloides/antagonistas & inibidores
Peptídeos beta-Amiloides/farmacologia
Animais
Astrócitos/citologia
Astrócitos/metabolismo
Córtex Cerebral/citologia
Córtex Cerebral/efeitos dos fármacos
Córtex Cerebral/metabolismo
Ácidos Cumáricos/química
Relação Dose-Resposta a Droga
Embrião de Mamíferos
Regulação da Expressão Gênica
Lipopolissacarídeos/antagonistas & inibidores
Lipopolissacarídeos/farmacologia
Monoglicerídeos/química
NF-kappa B/genética
NF-kappa B/metabolismo
Fármacos Neuroprotetores/química
Óxido Nítrico/biossíntese
Óxido Nítrico Sintase Tipo II/genética
Óxido Nítrico Sintase Tipo II/metabolismo
Cultura Primária de Células
Ratos
Transdução de Sinais
Solubilidade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (1-feruloylglycerol); 0 (Amyloid beta-Peptides); 0 (Coumaric Acids); 0 (Lipopolysaccharides); 0 (Monoglycerides); 0 (NF-kappa B); 0 (Neuroprotective Agents); 31C4KY9ESH (Nitric Oxide); AVM951ZWST (ferulic acid); EC 1.14.13.39 (Nitric Oxide Synthase Type II); EC 1.14.13.39 (Nos2 protein, rat)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170726
[Lr] Data última revisão:
170726
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170614
[St] Status:MEDLINE
[do] DOI:10.1080/09168451.2017.1336925


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[PMID]:28595901
[Au] Autor:González-Fernández MJ; Ramos-Bueno RP; Rodríguez-García I; Guil-Guerrero JL
[Ad] Endereço:Food Technology Division, Agrifood Campus of International Excellence, ceiA3, University of Almería, E-040120, Almería, Spain.
[Ti] Título:Purification process for MUFA- and PUFA-based monoacylglycerols from edible oils.
[So] Source:Biochimie;139:107-114, 2017 Aug.
[Is] ISSN:1638-6183
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:Important health benefits have been attributed to monoacylglycerols (MAGs) due to their various physiological functions, owing to which they become candidates for use as functional foods in order to prevent the onset of certain diseases such as colon cancer. In this work, six edible oils, namely: olive, linseed, sunflower, evening primrose, DHASCO and ARASCO have been processed to obtain different MUFA- and PUFA- based MAGs. First, the oils were hydrolyzed by means of an enzymatic process using porcine pancreatic lipase and then the reaction products were fractionated by using a liquid chromatography column containing silica gel as stationary phase in order to purify the MAGs-enriched fraction. A second chromatography process was performed using silver nitrate coated silica gel as stationary phase, in order to obtain the different MUFA- and PUFA-based MAGs from the corresponding oils. Overall, MAGs based on oleic, linoleic, α-linolenic, γ-linolenic, arachidonic and docosahexaenoic acids have been isolated in high yields and purities (92.6, 97.4, 95.3, 90.9, 100 and 95.3% purity, respectively). Positional distribution was determined by means of H NMR, which revealed a mix of 1(3) and 2-MAGs in variable proportions in the different MAGs.
[Mh] Termos MeSH primário: Ácidos Graxos Monoinsaturados/química
Ácidos Graxos Ômega-3/química
Monoglicerídeos/isolamento & purificação
Óleos Vegetais/química
[Mh] Termos MeSH secundário: Animais
Cromatografia Líquida
Lipase/metabolismo
Espectroscopia de Ressonância Magnética
Pâncreas/enzimologia
Suínos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Fatty Acids, Monounsaturated); 0 (Fatty Acids, Omega-3); 0 (Monoglycerides); 0 (Plant Oils); EC 3.1.1.3 (Lipase)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170912
[Lr] Data última revisão:
170912
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170610
[St] Status:MEDLINE


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[PMID]:28515375
[Au] Autor:Satou C; Goto H; Yamazaki Y; Saitou K; Matsumoto S; Takahashi O; Miyazaki Y; Ikuta K; Yajima Y
[Ad] Endereço:The Nisshin OilliO Group.
[Ti] Título:Modified Gas Chromatographic Method to Determine Monoacylglycerol and Diacylglycerol Contents in Edible Fats and Oils.
[So] Source:J Oleo Sci;66(6):601-606, 2017 Jun 01.
[Is] ISSN:1347-3352
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:Monoacylglycerol (MAG) and diacylglycerol (DAG) are minor components of edible fats and oils, and they relate to the quality of these foods. The AOCS official method Cd 11b-91 has been used to determine MAG and DAG contents in fats and oils. There are, however, difficulties in the determination of MAG and DAG using this analytical procedure. Therefore, we improved this method by modifying the trimethylsilyl derivatization procedure and replacing the internal standard (IS) material. In our modified method, TMS-HT (mixture of hexamethyldisilazane and trimethylchlorosilane) was used for derivatization of MAG and DAG, which was followed by liquid-liquid extraction with water and n-hexane solution containing the IS, tricaprin. Using the modified method, we demonstrated superior repeatability in comparison with that of the AOCS method by reducing procedural difficulties. The relative standard deviation of distearin peak areas was 1.8% or 2.9% in the modified method, while it was 5.6% in the AOCS method. In addition, capillary columns, such as DB-1ht and DB-5ht could be used in this method.
[Mh] Termos MeSH primário: Cromatografia Gasosa/métodos
Gorduras Insaturadas na Dieta/análise
Gorduras na Dieta/análise
Diglicerídeos/análise
Monoglicerídeos/análise
[Mh] Termos MeSH secundário: Qualidade dos Alimentos
Hexanos
Extração Líquido-Líquido/métodos
Compostos de Organossilício
Reprodutibilidade dos Testes
Soluções
Triglicerídeos
Compostos de Trimetilsilil
Água
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Dietary Fats); 0 (Dietary Fats, Unsaturated); 0 (Diglycerides); 0 (Hexanes); 0 (Monoglycerides); 0 (Organosilicon Compounds); 0 (Solutions); 0 (Triglycerides); 0 (Trimethylsilyl Compounds); 059QF0KO0R (Water); 2DDG612ED8 (n-hexane); 62UO4690X6 (trimethylchlorosilane); H36C68P1BH (hexamethylsilazane); O1PB8EU98M (tricaprin)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170825
[Lr] Data última revisão:
170825
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170519
[St] Status:MEDLINE
[do] DOI:10.5650/jos.ess16143


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[PMID]:28379543
[Au] Autor:Wang S; Sun H; Tanowitz M; Liang XH; Crooke ST
[Ad] Endereço:Department of Core Antisense Research, Ionis Pharmaceuticals, Inc. 2855 Gazelle Court, Carlsbad, CA 92010, USA.
[Ti] Título:Intra-endosomal trafficking mediated by lysobisphosphatidic acid contributes to intracellular release of phosphorothioate-modified antisense oligonucleotides.
[So] Source:Nucleic Acids Res;45(9):5309-5322, 2017 May 19.
[Is] ISSN:1362-4962
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Antisense oligonucleotides (ASOs) with phosphorothioate (PS) linkages are broadly used as research tools and therapeutic agents. Chemically modified PS-ASOs can mediate efficient target reduction by site-specific cleavage of RNA through RNase H1. PS-ASOs are known to be internalized via a number of endocytotic pathways and are released from membrane-enclosed endocytotic organelles, mainly late endosomes (LEs). This study was focused on the details of PS-ASO trafficking through endocytic pathways. It was found that lysobisphosphatidic acid (LBPA) is required for release of PS-ASOs from LEs. PS-ASOs exited early endosomes (EEs) rapidly after internalization and became co-localized with LBPA by 2 hours in LEs. Inside LEs, PS-ASOs and LBPA were co-localized in punctate, dot-like structures, likely intraluminal vesicles (ILVs). Deactivation of LBPA using anti-LBPA antibody significantly decreased PS-ASO activities without affecting total PS-ASO uptake. Reduction of Alix also substantially decreased PS-ASO activities without affecting total PS-ASO uptake. Furthermore, Alix reduction decreased LBPA levels and limited co-localization of LBPA with PS-ASOs at ILVs inside LEs. Thus, the fusion properties of ILVs, which are supported by LBPA, contribute to PS-ASO intracellular release from LEs.
[Mh] Termos MeSH primário: Endossomos/metabolismo
Espaço Intracelular/metabolismo
Lisofosfolipídeos/metabolismo
Monoglicerídeos/metabolismo
Oligonucleotídeos Antissenso/metabolismo
Oligonucleotídeos Fosforotioatos/metabolismo
[Mh] Termos MeSH secundário: Transporte Biológico
Proteínas de Ligação ao Cálcio/metabolismo
Proteínas de Transporte/metabolismo
Proteínas de Ciclo Celular/metabolismo
Linhagem Celular Tumoral
Endocitose
Complexos Endossomais de Distribuição Requeridos para Transporte/metabolismo
Seres Humanos
Cinética
Glicoproteínas de Membrana/metabolismo
Modelos Biológicos
Oligonucleotídeos Antissenso/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Calcium-Binding Proteins); 0 (Carrier Proteins); 0 (Cell Cycle Proteins); 0 (Endosomal Sorting Complexes Required for Transport); 0 (Lysophospholipids); 0 (Membrane Glycoproteins); 0 (Monoglycerides); 0 (NPC1 protein, human); 0 (Oligonucleotides, Antisense); 0 (PDCD6IP protein, human); 0 (Phosphorothioate Oligonucleotides); 0 (bis(monoacylglyceryl)phosphate)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170926
[Lr] Data última revisão:
170926
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170406
[St] Status:MEDLINE
[do] DOI:10.1093/nar/gkx231


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[PMID]:28348274
[Au] Autor:Billeskov R; Wang Y; Solaymani-Mohammadi S; Frey B; Kulkarni S; Andersen P; Agger EM; Sui Y; Berzofsky JA
[Ad] Endereço:Vaccine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; rob@ssi.dk berzofsj@mail.nih.gov.
[Ti] Título:Low Antigen Dose in Adjuvant-Based Vaccination Selectively Induces CD4 T Cells with Enhanced Functional Avidity and Protective Efficacy.
[So] Source:J Immunol;198(9):3494-3506, 2017 May 01.
[Is] ISSN:1550-6606
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:T cells with high functional avidity can sense and respond to low levels of cognate Ag, a characteristic that is associated with more potent responses against tumors and many infections, including HIV. Although an important determinant of T cell efficacy, it has proven difficult to selectively induce T cells of high functional avidity through vaccination. Attempts to induce high-avidity T cells by low-dose in vivo vaccination failed because this strategy simply gave no response. Instead, selective induction of high-avidity T cells has required in vitro culturing of specific T cells with low Ag concentrations. In this study, we combined low vaccine Ag doses with a novel potent cationic liposomal adjuvant, cationic adjuvant formulation 09, consisting of dimethyldioctadecylammonium liposomes incorporating two immunomodulators (monomycolyl glycerol analog and polyinosinic-polycytidylic acid) that efficiently induces CD4 Th cells, as well as cross-primes CD8 CTL responses. We show that vaccination with low Ag dose selectively primes CD4 T cells of higher functional avidity, whereas CD8 T cell functional avidity was unrelated to vaccine dose in mice. Importantly, CD4 T cells of higher functional avidity induced by low-dose vaccinations showed higher cytokine release per cell and lower inhibitory receptor expression (PD-1, CTLA-4, and the apoptosis-inducing Fas death receptor) compared with their lower-avidity CD4 counterparts. Notably, increased functional CD4 T cell avidity improved antiviral efficacy of CD8 T cells. These data suggest that potent adjuvants, such as cationic adjuvant formulation 09, render low-dose vaccination a feasible and promising approach for generating high-avidity T cells through vaccination.
[Mh] Termos MeSH primário: Vacinas contra a AIDS/imunologia
Adjuvantes Imunológicos/administração & dosagem
Linfócitos T CD4-Positivos/imunologia
Antígenos HIV/imunologia
HIV/metabolismo
Lipossomos/administração & dosagem
Poli I-C/administração & dosagem
[Mh] Termos MeSH secundário: Animais
Linfócitos T CD8-Positivos/imunologia
Células Cultivadas
Citocinas/metabolismo
HIV/imunologia
Seres Humanos
Lipossomos/química
Ativação Linfocitária
Camundongos
Camundongos Endogâmicos BALB C
Camundongos Endogâmicos C57BL
Monoglicerídeos/química
Compostos de Amônio Quaternário/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (AIDS Vaccines); 0 (Adjuvants, Immunologic); 0 (Cytokines); 0 (HIV Antigens); 0 (Liposomes); 0 (Monoglycerides); 0 (Quaternary Ammonium Compounds); 0 (monomycoloyl glycerol); 251IW5I21C (dimethyldioctadecylammonium); O84C90HH2L (Poly I-C)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170329
[St] Status:MEDLINE
[do] DOI:10.4049/jimmunol.1600965


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[PMID]:28333463
[Au] Autor:Ogihara T; Amano N; Mitsui Y; Fujino K; Ohta H; Takahashi K; Matsuura H
[Ad] Endereço:Research Faculty of Agriculture, Hokkaido University , Sapporo 060-8589, Japan.
[Ti] Título:Determination of the Absolute Configuration of a Monoglyceride Antibolting Compound and Isolation of Related Compounds from Radish Leaves (Raphanus sativus).
[So] Source:J Nat Prod;80(4):872-878, 2017 Apr 28.
[Is] ISSN:1520-6025
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:A monoglyceride (1) has been reported to possess an antibolting effect in radish (Raphanus sativus), but its absolute configuration at the C-2 position was not determined earlier. In this work, the absolute configuration of 1 was determined to be (2S), and it was also accompanied by one new (2) and two known monoglycerides (3 and 4). The chemical structure of 2 was determined as ß-(7'Z,10'Z,13'Z)-hexadecatrienoic acid monoglyceride (ß-16:3 monoglyceride). Qualitative and quantitative analytical methods for compounds 1-4 were developed, using two deuterium-labeled compounds (8 and 9) as internal standards. The results revealed a broader range of distribution of 1-4 in several annual winter crops. It was also found that these isolated compounds have an inhibitory effect on the root elongation of Arabidopsis thaliana seedlings at concentrations of 25 and 50 µM in the medium. However, the inhibitory effect of 1 was not dependent on coronatin-insensitive 1 (COI1) protein, which may suggest the involvement of an unidentified signaling system other than jasmonic acid signaling.
[Mh] Termos MeSH primário: Ácidos Graxos Insaturados/química
Monoglicerídeos/isolamento & purificação
Monoglicerídeos/farmacologia
Raphanus/química
[Mh] Termos MeSH secundário: Arabidopsis/efeitos dos fármacos
Glicerídeos/farmacologia
Estrutura Molecular
Monoglicerídeos/química
Ressonância Magnética Nuclear Biomolecular
Folhas de Planta/química
Raízes de Plantas/química
Raízes de Plantas/efeitos dos fármacos
Estereoisomerismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 ((7'Z,10'Z,13'Z)-hexadecatrienoic acid monoglyceride); 0 (Fatty Acids, Unsaturated); 0 (Glycerides); 0 (Monoglycerides)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170801
[Lr] Data última revisão:
170801
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170324
[St] Status:MEDLINE
[do] DOI:10.1021/acs.jnatprod.6b00746


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[PMID]:28126847
[Au] Autor:Abdul-Hammed M; Breiden B; Schwarzmann G; Sandhoff K
[Ad] Endereço:Life and Medical Sciences (LIMES) Institut, Membrane Biology and Lipid Biochemistry Unit, Kekulé-Institut für Organische Chemie und Biochemie, Universität Bonn, Bonn, Germany.
[Ti] Título:Lipids regulate the hydrolysis of membrane bound glucosylceramide by lysosomal ß-glucocerebrosidase.
[So] Source:J Lipid Res;58(3):563-577, 2017 Mar.
[Is] ISSN:1539-7262
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Glucosylceramide (GlcCer) is the primary storage lipid in the lysosomes of Gaucher patients and a secondary one in Niemann-Pick disease types A, B, and C. The regulatory roles of lipids on the hydrolysis of membrane bound GlcCer by lysosomal ß-glucocerebrosidase (GBA1) was probed using a detergent-free liposomal assay. The degradation rarely occurs at uncharged liposomal surfaces in the absence of saposin (Sap) C. However, anionic lipids stimulate GlcCer hydrolysis at low pH by up to 1,000-fold depending on the nature and position of the negative charges in their head groups while cationic lipids inhibit the degradation, thus showing the importance of electrostatic interactions between the polycationic GBA1 and the negatively charged vesicle surfaces at low pH. Ceramide, fatty acids, monoacylglycerol, and diacylglycerol also stimulate GlcCer hydrolysis while SM, sphingosine, and sphinganine play strong inhibitory roles, thereby explaining the secondary storage of GlcCer in Niemann-Pick diseases. Surprisingly, cholesterol stimulates GlcCer degradation in the presence of bis(monoacylglycero)phosphate (BMP). Sap C strongly stimulates GlcCer hydrolysis even in the absence of BMP and the regulatory roles of the intraendolysosomal lipids on its activity is discussed. Our data suggest that these strong modifiers of GlcCer hydrolysis affect the genotype-phenotype correlation in several cases of Gaucher patients independent of the types.
[Mh] Termos MeSH primário: Doença de Gaucher/metabolismo
Glucosilceramidase/genética
Glucosilceramidas/metabolismo
Doenças de Niemann-Pick/metabolismo
[Mh] Termos MeSH secundário: Colesterol/metabolismo
Doença de Gaucher/genética
Doença de Gaucher/patologia
Estudos de Associação Genética
Glucosilceramidase/metabolismo
Seres Humanos
Hidrólise
Metabolismo dos Lipídeos/genética
Lisofosfolipídeos/metabolismo
Lisossomos/enzimologia
Monoglicerídeos/metabolismo
Doenças de Niemann-Pick/genética
Doenças de Niemann-Pick/patologia
Saposinas/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Glucosylceramides); 0 (Lysophospholipids); 0 (Monoglycerides); 0 (Saposins); 0 (bis(monoacylglyceryl)phosphate); 97C5T2UQ7J (Cholesterol); EC 3.2.1.45 (Glucosylceramidase)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170828
[Lr] Data última revisão:
170828
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170128
[St] Status:MEDLINE
[do] DOI:10.1194/jlr.M073510



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