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[PMID]:28771546
[Au] Autor:Sun H; Li F; Xu Z; Sun M; Cong H; Qiao F; Zhong X
[Ad] Endereço:Key Laboratory of Crop Gene Resources and Germplasm Enhancement in Southern China, Ministry of Agriculture / Tropical Crops Genetic Resources Institute, Chinese Academy of Tropical Agricultural Sciences, Danzhou, China.
[Ti] Título:De novo leaf and root transcriptome analysis to identify putative genes involved in triterpenoid saponins biosynthesis in Hedera helix L.
[So] Source:PLoS One;12(8):e0182243, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Hedera helix L. is an important traditional medicinal plant in Europe. The main active components are triterpenoid saponins, but none of the potential enzymes involved in triterpenoid saponins biosynthesis have been discovered and annotated. Here is reported the first study of global transcriptome analyses using the Illumina HiSeq™ 2500 platform for H. helix. In total, over 24 million clean reads were produced and 96,333 unigenes were assembled, with an average length of 1385 nt; more than 79,085 unigenes had at least one significant match to an existing gene model. Differentially Expressed Gene analysis identified 6,222 and 7,012 unigenes which were expressed either higher or lower in leaf samples when compared with roots. After functional annotation and classification, two pathways and 410 unigenes related to triterpenoid saponins biosynthesis were discovered. The accuracy of these de novo sequences was validated by RT-qPCR analysis and a RACE clone. These data will enrich our knowledge of triterpenoid saponin biosynthesis and provide a theoretical foundation for molecular research on H. helix.
[Mh] Termos MeSH primário: Hedera/genética
Folhas de Planta/genética
Raízes de Plantas/genética
Saponinas/biossíntese
Saponinas/genética
Transcriptoma
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
DNA Complementar/química
DNA Complementar/metabolismo
Perfilação da Expressão Gênica
Hedera/metabolismo
Hidroximetilglutaril-CoA-Redutases NADP-Dependentes/química
Hidroximetilglutaril-CoA-Redutases NADP-Dependentes/genética
Hidroximetilglutaril-CoA-Redutases NADP-Dependentes/metabolismo
Folhas de Planta/metabolismo
Proteínas de Plantas/química
Proteínas de Plantas/genética
Proteínas de Plantas/metabolismo
Raízes de Plantas/metabolismo
RNA de Plantas/isolamento & purificação
RNA de Plantas/metabolismo
Reação em Cadeia da Polimerase em Tempo Real
Análise de Sequência de DNA
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (DNA, Complementary); 0 (Plant Proteins); 0 (RNA, Plant); 0 (Saponins); EC 1.1.1.34 (Hydroxymethylglutaryl-CoA-Reductases, NADP-dependent)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171013
[Lr] Data última revisão:
171013
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170804
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0182243


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[PMID]:28263378
[Au] Autor:Robertlee J; Kobayashi K; Suzuki M; Muranaka T
[Ad] Endereço:Department of Biotechnology, Graduate School of Engineering, Osaka University, Suita, Japan.
[Ti] Título:AKIN10, a representative Arabidopsis SNF1-related protein kinase 1 (SnRK1), phosphorylates and downregulates plant HMG-CoA reductase.
[So] Source:FEBS Lett;591(8):1159-1166, 2017 Apr.
[Is] ISSN:1873-3468
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:HMG-CoA reductase (HMGR) is a key enzyme in the mevalonate pathway for sterols and cytosolic isoprenoid production. Although HMGR kinases from spinach, barley, and cauliflower tissues have been strongly suggested as members of SNF1-related protein kinases 1 (SnRK1), the phosphorylation and inactivation of HMGR by plant SnRK1s has not been demonstrated. In this study, we elucidated that AKIN10, an Arabidopsis SnRK1, acts as an HMGR kinase. The recombinant AKIN10 phosphorylates and inactivates AtHMGR1S using recombinant GRIK1 as the AKIN10 activator. In contrast, AKIN10-GRIK1 fails to inactivate AtHMGR1S-S577A, suggesting that this is achieved through Ser577 phosphorylation. Moreover, phosphorylation is detected not only in AtHMGR1S but also in AtHMGR1S-S577A, suggesting the presence of a novel regulatory mechanism of plant HMGR.
[Mh] Termos MeSH primário: Proteínas de Arabidopsis/antagonistas & inibidores
Proteínas de Arabidopsis/metabolismo
Arabidopsis/enzimologia
Regulação da Expressão Gênica de Plantas
Processamento de Proteína Pós-Traducional
Proteínas Serina-Treonina Quinases/metabolismo
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Substituição de Aminoácidos
Arabidopsis/metabolismo
Proteínas de Arabidopsis/química
Proteínas de Arabidopsis/genética
Domínio Catalítico
Sequência Conservada
Ativação Enzimática
Repressão Enzimática
Hevea/enzimologia
Hidroximetilglutaril-CoA-Redutases NADP-Dependentes/química
Hidroximetilglutaril-CoA-Redutases NADP-Dependentes/genética
Hidroximetilglutaril-CoA-Redutases NADP-Dependentes/metabolismo
Mutação
Fragmentos de Peptídeos/antagonistas & inibidores
Fragmentos de Peptídeos/genética
Fragmentos de Peptídeos/metabolismo
Fosforilação
Proteínas de Plantas/antagonistas & inibidores
Proteínas de Plantas/química
Proteínas de Plantas/genética
Proteínas de Plantas/metabolismo
Domínios e Motivos de Interação entre Proteínas
Proteínas Serina-Treonina Quinases/química
Proteínas Serina-Treonina Quinases/genética
Proteínas Recombinantes/metabolismo
Serina/metabolismo
Especificidade por Substrato
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Arabidopsis Proteins); 0 (Peptide Fragments); 0 (Plant Proteins); 0 (Recombinant Proteins); 452VLY9402 (Serine); EC 1.1.1.34 (HMGR protein, Arabidopsis); EC 1.1.1.34 (Hydroxymethylglutaryl-CoA-Reductases, NADP-dependent); EC 2.7.11.1 (GRIK1 protein, Arabidopsis); EC 2.7.11.1 (Protein-Serine-Threonine Kinases); EC 2.7.11.1 (SnRK1 protein, Arabidopsis)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170808
[Lr] Data última revisão:
170808
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170307
[St] Status:MEDLINE
[do] DOI:10.1002/1873-3468.12618


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[PMID]:27834848
[Au] Autor:Li Y; Zhao X; Feng X; Liu X; Deng C; Hu CH
[Ad] Endereço:School of Pharmaceutical Sciences, Southwest University, Chongqing 400715, China. anlan8934@email.swu.edu.cn.
[Ti] Título:Berberine Alleviates Olanzapine-Induced Adipogenesis via the AMPKα-SREBP Pathway in 3T3-L1 Cells.
[So] Source:Int J Mol Sci;17(11), 2016 Nov 09.
[Is] ISSN:1422-0067
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:The aim of this study was to investigate the mechanisms underlying the inhibitory effects of berberine (BBR) on olanzapine (OLZ)-induced adipogenesis in a well-replicated 3T3-L1 cell model. Oil-Red-O (ORO) staining showed that BBR significantly decreased OLZ-induced adipogenesis. Co-treatment with OLZ and BBR decreased the accumulation of triglyceride (TG) and total cholesterol (TC) by 55.58% ± 3.65% and 49.84% ± 8.31%, respectively, in 3T3-L1 adipocytes accompanied by reduced expression of Sterol regulatory element binding proteins 1 (SREBP1), fatty acid synthase (FAS), peroxisome proliferator activated receptor-γ (PPARγ), SREBP2, low-density lipoprotein receptor (LDLR), and hydroxymethylglutaryl-coenzyme A reductase (HMGR) genes compared with OLZ alone. Consistently, the co-treatment downregulated protein levels of SREBP1, SREBP2, and LDLR by 57.71% ± 9.42%, 73.05% ± 11.82%, and 59.46% ± 9.91%, respectively. In addition, co-treatment reversed the phosphorylation level of AMP-activated protein kinase-α (AMPKα), which was reduced by OLZ, determined via the ratio of pAMPKα:AMPKα (94.1%) compared with OLZ alone. The results showed that BBR may prevent lipid metabolism disorders caused by OLZ by reversing the degree of SREBP pathway upregulated and the phosphorylation of AMPKα downregulated. Collectively, these results indicated that BBR could be used as a potential adjuvant to prevent dyslipidemia and obesity caused by the use of second-generation antipsychotic medication.
[Mh] Termos MeSH primário: Proteínas Quinases Ativadas por AMP/genética
Adipócitos/efeitos dos fármacos
Antipsicóticos/antagonistas & inibidores
Benzodiazepinas/antagonistas & inibidores
Berberina/farmacologia
Hipolipemiantes/farmacologia
Proteína de Ligação a Elemento Regulador de Esterol 1/genética
[Mh] Termos MeSH secundário: Células 3T3-L1
Proteínas Quinases Ativadas por AMP/metabolismo
Adipócitos/citologia
Adipócitos/metabolismo
Adipogenia/efeitos dos fármacos
Adipogenia/genética
Animais
Antipsicóticos/farmacologia
Benzodiazepinas/farmacologia
Diferenciação Celular
Colesterol/biossíntese
Ácido Graxo Sintase Tipo I/genética
Ácido Graxo Sintase Tipo I/metabolismo
Regulação da Expressão Gênica
Hidroximetilglutaril-CoA-Redutases NADP-Dependentes/genética
Hidroximetilglutaril-CoA-Redutases NADP-Dependentes/metabolismo
Metabolismo dos Lipídeos/efeitos dos fármacos
Metabolismo dos Lipídeos/genética
Camundongos
PPAR gama/genética
PPAR gama/metabolismo
Fosforilação/efeitos dos fármacos
Receptores de LDL/genética
Receptores de LDL/metabolismo
Transdução de Sinais
Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo
Proteína de Ligação a Elemento Regulador de Esterol 2/genética
Proteína de Ligação a Elemento Regulador de Esterol 2/metabolismo
Triglicerídeos/antagonistas & inibidores
Triglicerídeos/biossíntese
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antipsychotic Agents); 0 (Hypolipidemic Agents); 0 (PPAR gamma); 0 (Receptors, LDL); 0 (Srebf1 protein, mouse); 0 (Srebf2 protein, mouse); 0 (Sterol Regulatory Element Binding Protein 1); 0 (Sterol Regulatory Element Binding Protein 2); 0 (Triglycerides); 0I8Y3P32UF (Berberine); 12794-10-4 (Benzodiazepines); 97C5T2UQ7J (Cholesterol); EC 1.1.1.34 (Hydroxymethylglutaryl-CoA-Reductases, NADP-dependent); EC 2.3.1.85 (Fatty Acid Synthase, Type I); EC 2.7.11.1 (AMPK alpha1 subunit, mouse); EC 2.7.11.31 (AMP-Activated Protein Kinases); N7U69T4SZR (olanzapine)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161112
[St] Status:MEDLINE


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[PMID]:27392312
[Au] Autor:Cartocci V; Segatto M; Di Tunno I; Leone S; Pfrieger FW; Pallottini V
[Ad] Endereço:Department of Science, Biomedical and Technology Science Section, University Roma Tre, Viale Marconi, 446, 00146, Rome, Italy.
[Ti] Título:Modulation of the Isoprenoid/Cholesterol Biosynthetic Pathway During Neuronal Differentiation In Vitro.
[So] Source:J Cell Biochem;117(9):2036-44, 2016 09.
[Is] ISSN:1097-4644
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:During differentiation, neurons acquire their typical shape and functional properties. At present, it is unclear, whether this important developmental step involves metabolic changes. Here, we studied the contribution of the mevalonate (MVA) pathway to neuronal differentiation using the mouse neuroblastoma cell line N1E-115 as experimental model. Our results show that during differentiation, the activity of 3-hydroxy 3-methylglutaryl Coenzyme A reductase (HMGR), a key enzyme of MVA pathway, and the level of Low Density Lipoprotein receptor (LDLr) decrease, whereas the level of LDLr-related protein-1 (LRP1) and the dimerization of Scavanger Receptor B1 (SRB-1) rise. Pharmacologic inhibition of HMGR by simvastatin accelerated neuronal differentiation by modulating geranylated proteins. Collectively, our data suggest that during neuronal differentiation, the activity of the MVA pathway decreases and we postulate that any interference with this process impacts neuronal morphology and function. Therefore, the MVA pathway appears as an attractive pharmacological target to modulate neurological and metabolic symptoms of developmental neuropathologies. J. Cell. Biochem. 117: 2036-2044, 2016. © 2016 Wiley Periodicals, Inc.
[Mh] Termos MeSH primário: Diferenciação Celular/fisiologia
Colesterol/biossíntese
Neurônios/metabolismo
Terpenos/metabolismo
[Mh] Termos MeSH secundário: Animais
Diferenciação Celular/efeitos dos fármacos
Linhagem Celular Tumoral
Colesterol/genética
Hidroximetilglutaril-CoA-Redutases NADP-Dependentes/genética
Hidroximetilglutaril-CoA-Redutases NADP-Dependentes/metabolismo
Camundongos
Receptores de LDL/genética
Receptores de LDL/metabolismo
Receptores Depuradores Classe B/genética
Receptores Depuradores Classe B/metabolismo
Sinvastatina/farmacologia
Proteínas Supressoras de Tumor/genética
Proteínas Supressoras de Tumor/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Lrp1 protein, mouse); 0 (Receptors, LDL); 0 (Scarb1 protein, mouse); 0 (Scavenger Receptors, Class B); 0 (Terpenes); 0 (Tumor Suppressor Proteins); 97C5T2UQ7J (Cholesterol); AGG2FN16EV (Simvastatin); EC 1.1.1.34 (Hydroxymethylglutaryl-CoA-Reductases, NADP-dependent)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171110
[Lr] Data última revisão:
171110
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160709
[St] Status:MEDLINE
[do] DOI:10.1002/jcb.25500


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[PMID]:27133788
[Au] Autor:Lipko A; Swiezewska E
[Ad] Endereço:Institute of Biochemistry and Biophysics, Polish Academy of Sciences, 02-106 Warsaw, Poland. Electronic address: ag.lipko@ibb.waw.pl.
[Ti] Título:Isoprenoid generating systems in plants - A handy toolbox how to assess contribution of the mevalonate and methylerythritol phosphate pathways to the biosynthetic process.
[So] Source:Prog Lipid Res;63:70-92, 2016 07.
[Is] ISSN:1873-2194
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Isoprenoids comprise an astonishingly diverse group of metabolites with numerous potential and actual applications in medicine, agriculture and the chemical industry. Generation of efficient platforms producing isoprenoids is a target of numerous laboratories. Such efforts are generally enhanced if the native biosynthetic routes can be identified, and if the regulatory mechanisms responsible for the biosynthesis of the compound(s) of interest can be determined. In this review a critical summary of the techniques applied to establish the contribution of the two alternative routes of isoprenoid production operating in plant cells, the mevalonate and methylerythritol pathways, with a focus on their co-operation (cross-talk) is presented. Special attention has been paid to methodological aspects of the referred studies, in order to give the reader a deeper understanding for the nuances of these powerful techniques. This review has been designed as an organized toolbox, which might offer the researchers comments useful both for project design and for interpretation of results obtained.
[Mh] Termos MeSH primário: Eritritol/metabolismo
Ácido Mevalônico/metabolismo
Plantas/metabolismo
Terpenos/metabolismo
[Mh] Termos MeSH secundário: Acetil-CoA C-Acetiltransferase/genética
Acetil-CoA C-Acetiltransferase/metabolismo
Carboxiliases/genética
Carboxiliases/metabolismo
Eritritol/análogos & derivados
Hidroximetilglutaril-CoA-Redutases NADP-Dependentes/genética
Hidroximetilglutaril-CoA-Redutases NADP-Dependentes/metabolismo
Redes e Vias Metabólicas
Proteínas de Plantas/genética
Proteínas de Plantas/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; REVIEW
[Nm] Nome de substância:
0 (Plant Proteins); 0 (Terpenes); EC 1.1.1.34 (Hydroxymethylglutaryl-CoA-Reductases, NADP-dependent); EC 2.3.1.9 (Acetyl-CoA C-Acetyltransferase); EC 4.1.1.- (Carboxy-Lyases); EC 4.1.1.33 (pyrophosphomevalonate decarboxylase); RA96B954X6 (Erythritol); S5UOB36OCZ (Mevalonic Acid)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170420
[Lr] Data última revisão:
170420
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160503
[St] Status:MEDLINE


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[PMID]:26589673
[Au] Autor:Mertens J; Pollier J; Vanden Bossche R; Lopez-Vidriero I; Franco-Zorrilla JM; Goossens A
[Ad] Endereço:Department of Plant Systems Biology, VIB, B-9052 Ghent, Belgium (J.M., J.P., R.V.B., A.G.);Department of Plant Biotechnology and Bioinformatics, Ghent University, B-9052 Ghent, Belgium (J.M., J.P., R.V.B., A.G.); andGenomics Unit, Centro Nacional de Biotecnología-Consejo Superior de Investigaciones
[Ti] Título:The bHLH Transcription Factors TSAR1 and TSAR2 Regulate Triterpene Saponin Biosynthesis in Medicago truncatula.
[So] Source:Plant Physiol;170(1):194-210, 2016 Jan.
[Is] ISSN:1532-2548
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Plants respond to stresses by producing a broad spectrum of bioactive specialized metabolites. Hormonal elicitors, such as jasmonates, trigger a complex signaling circuit leading to the concerted activation of specific metabolic pathways. However, for many specialized metabolic pathways, the transcription factors involved remain unknown. Here, we report on two homologous jasmonate-inducible transcription factors of the basic helix-loop-helix family, TRITERPENE SAPONIN BIOSYNTHESIS ACTIVATING REGULATOR1 (TSAR1) and TSAR2, which direct triterpene saponin biosynthesis in Medicago truncatula. TSAR1 and TSAR2 are coregulated with and transactivate the genes encoding 3-HYDROXY-3-METHYLGLUTARYL-COENZYME A REDUCTASE1 (HMGR1) and MAKIBISHI1, the rate-limiting enzyme for triterpene biosynthesis and an E3 ubiquitin ligase that controls HMGR1 levels, respectively. Transactivation is mediated by direct binding of TSARs to the N-box in the promoter of HMGR1. In transient expression assays in tobacco (Nicotiana tabacum) protoplasts, TSAR1 and TSAR2 exhibit different patterns of transactivation of downstream triterpene saponin biosynthetic genes, hinting at distinct functionalities within the regulation of the pathway. Correspondingly, overexpression of TSAR1 or TSAR2 in M. truncatula hairy roots resulted in elevated transcript levels of known triterpene saponin biosynthetic genes and strongly increased the accumulation of triterpene saponins. TSAR2 overexpression specifically boosted hemolytic saponin biosynthesis, whereas TSAR1 overexpression primarily stimulated nonhemolytic soyasaponin biosynthesis. Both TSARs also activated all genes of the precursor mevalonate pathway but did not affect sterol biosynthetic genes, pointing to their specific role as regulators of specialized triterpene metabolism in M. truncatula.
[Mh] Termos MeSH primário: Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo
Medicago truncatula/metabolismo
Proteínas de Plantas/metabolismo
Saponinas/biossíntese
[Mh] Termos MeSH secundário: Sítios de Ligação
Ciclopentanos/metabolismo
Regulação da Expressão Gênica de Plantas
Hidroximetilglutaril-CoA-Redutases NADP-Dependentes/genética
Hidroximetilglutaril-CoA-Redutases NADP-Dependentes/metabolismo
Medicago truncatula/genética
Ácido Mevalônico/metabolismo
Oxilipinas/metabolismo
Proteínas de Plantas/genética
Raízes de Plantas/genética
Raízes de Plantas/metabolismo
Plantas Geneticamente Modificadas
Regiões Promotoras Genéticas
Saponinas/genética
Saponinas/metabolismo
Análise de Sequência de RNA
Tabaco/genética
Triterpenos/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Basic Helix-Loop-Helix Transcription Factors); 0 (Cyclopentanes); 0 (Oxylipins); 0 (Plant Proteins); 0 (Saponins); 0 (Triterpenes); 6RI5N05OWW (jasmonic acid); EC 1.1.1.34 (Hydroxymethylglutaryl-CoA-Reductases, NADP-dependent); S5UOB36OCZ (Mevalonic Acid)
[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:151122
[St] Status:MEDLINE
[do] DOI:10.1104/pp.15.01645


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[PMID]:26287401
[Au] Autor:Wang K; Bao L; Xiong W; Ma K; Han J; Wang W; Yin W; Liu H
[Ad] Endereço:State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences , No. 1 Beichenxi Road, Chaoyang District, Beijing 100101, People's Republic of China.
[Ti] Título:Lanostane Triterpenes from the Tibetan Medicinal Mushroom Ganoderma leucocontextum and Their Inhibitory Effects on HMG-CoA Reductase and α-Glucosidase.
[So] Source:J Nat Prod;78(8):1977-89, 2015 Aug 28.
[Is] ISSN:1520-6025
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Sixteen new lanostane triterpenes, ganoleucoins A-P (1-16), together with 10 known tripterpenes (17-26), were isolated from the cultivated fruiting bodies of Ganoderma leucocontextum, a new member of the Ganoderma lucidum complex. The structures of the new compounds were elucidated by extensive spectroscopic analysis and chemical transformation. The inhibitory effects of 1-26 on HMG-CoA reductase and α-glucosidase were tested in vitro. Compounds 1, 3, 6, 10-14, 17, 18, 23, 25, and 26 showed much stronger inhibitory activity against HMG-CoA reductase than the positive control atorvastatin. Compounds 13, 14, and 16 presented potent inhibitory activity against α-glucosidase from yeast with IC50 values of 13.6, 2.5, and 5.9 µM, respectively. In addition, the cytotoxicity of 1-26 was evaluated against the K562 and PC-3 cell lines by the MTT assay. Compounds 1, 2, 6, 7, 10, 12, 16, 18, and 25 exhibited cytotoxicity against K562 cells with IC50 values in the range 10-20 µM. Paclitaxel was used as the positive control with an IC50 value of 0.9 µM. This is the first report of secondary metabolites from this medicinal mushroom.
[Mh] Termos MeSH primário: Agaricales/química
Ganoderma/química
Inibidores de Glicosídeo Hidrolases/isolamento & purificação
Inibidores de Glicosídeo Hidrolases/farmacologia
Hidroximetilglutaril-CoA-Redutases NADP-Dependentes/efeitos dos fármacos
Triterpenos/isolamento & purificação
Triterpenos/farmacologia
[Mh] Termos MeSH secundário: Acil Coenzima A/efeitos dos fármacos
Carpóforos/química
Inibidores de Glicosídeo Hidrolases/química
Seres Humanos
Hidroximetilglutaril-CoA Redutases/efeitos dos fármacos
Concentração Inibidora 50
Células K562
Estrutura Molecular
Paclitaxel/farmacologia
Tibet
Triterpenos/química
alfa-Glucosidases/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Acyl Coenzyme A); 0 (Glycoside Hydrolase Inhibitors); 0 (Triterpenes); 1553-55-5 (3-hydroxy-3-methylglutaryl-coenzyme A); EC 1.1.1.- (Hydroxymethylglutaryl CoA Reductases); EC 1.1.1.34 (Hydroxymethylglutaryl-CoA-Reductases, NADP-dependent); EC 3.2.1.20 (alpha-Glucosidases); P88XT4IS4D (Paclitaxel)
[Em] Mês de entrada:1511
[Cu] Atualização por classe:150828
[Lr] Data última revisão:
150828
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150820
[St] Status:MEDLINE
[do] DOI:10.1021/acs.jnatprod.5b00331


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[PMID]:26254184
[Au] Autor:Mendoza-Poudereux I; Kutzner E; Huber C; Segura J; Eisenreich W; Arrillaga I
[Ad] Endereço:Departamento de Biología Vegetal, ISIC/ERI de Biotecnología y Biomedicina BIOTECMED, Universidad de Valencia, Av. Vicent Andrés Estellés s/n, 46100 Burjasot, Valencia, Spain.
[Ti] Título:Metabolic cross-talk between pathways of terpenoid backbone biosynthesis in spike lavender.
[So] Source:Plant Physiol Biochem;95:113-20, 2015 Oct.
[Is] ISSN:1873-2690
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:The metabolic cross-talk between the mevalonate (MVA) and the methylerythritol phosphate (MEP) pathways in developing spike lavender (Lavandula latifolia Med) was analyzed using specific inhibitors and on the basis of (13)C-labeling experiments. The presence of mevinolin (MEV), an inhibitor of the MVA pathway, at concentrations higher than 0.5 µM significantly reduced plant development, but not the synthesis of chlorophylls and carotenoids. On the other hand, fosmidomycin (FSM), an inhibitor of the MEP pathway, at concentrations higher than 20 µM blocked the synthesis of chlorophyll, carotenoids and essential oils, and significantly reduced stem development. Notably, 1.2 mM MVA could recover the phenotype of MEV-treated plants, including the normal growth and development of roots, and could partially restore the biosynthesis of photosynthetic pigments and, to a lesser extent, of the essential oils in plantlets treated with FSM. Spike lavender shoot apices were also used in (13)C-labeling experiments, where the plantlets were grown in the presence of [U-(13)C6]glucose. GC-MS-analysis of 1,8-cineole and camphor indicated that the C5-precursors, isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP) of both monoterpenes are predominantly biosynthesized via the methylerythritol phosphate (MEP) pathway. However, on the basis of the isotopologue profiles, a minor contribution of the MVA pathway was evident that was increased in transgenic spike lavender plants overexpressing the 3-hydroxy-3-methylglutaryl CoA reductase (HMGR), the first enzyme of the MVA pathway. Together, these findings provide evidence for a transport of MVA-derived precursors from the cytosol to the plastids in leaves of spike lavender.
[Mh] Termos MeSH primário: Lavandula/metabolismo
Brotos de Planta/metabolismo
Terpenos/metabolismo
[Mh] Termos MeSH secundário: Hidroximetilglutaril-CoA-Redutases NADP-Dependentes/genética
Hidroximetilglutaril-CoA-Redutases NADP-Dependentes/metabolismo
Lavandula/genética
Proteínas de Plantas/genética
Proteínas de Plantas/metabolismo
Brotos de Planta/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Plant Proteins); 0 (Terpenes); EC 1.1.1.34 (Hydroxymethylglutaryl-CoA-Reductases, NADP-dependent)
[Em] Mês de entrada:1605
[Cu] Atualização por classe:161020
[Lr] Data última revisão:
161020
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150809
[St] Status:MEDLINE


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[PMID]:26070251
[Au] Autor:Delang L; Scheers E; Grabner M; Verpaalen B; Helsen N; Vanstreels E; Daelemans D; Verfaillie C; Neyts J
[Ad] Endereço:Rega Institute for Medical Research, University of Leuven, Minderbroedersstraat 10, 3000 Leuven, Belgium. Electronic address: Leen.Delang@rega.kuleuven.be.
[Ti] Título:Understanding the molecular mechanism of host-based statin resistance in hepatitis C virus replicon containing cells.
[So] Source:Biochem Pharmacol;96(3):190-201, 2015 Aug 01.
[Is] ISSN:1873-2968
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:A number of statins, the cholesterol-lowering drugs, inhibit the in vitro replication of hepatitis C virus (HCV). In HCV-infected patients, addition of statins to the earlier standard of care therapy (pegIFN-α and ribavirin) resulted in increased sustained virological response rates. The mechanism by which statins inhibit HCV replication has not yet been elucidated. In an attempt to gain insight in the underlying mechanism, hepatoma cells carrying an HCV replicon were passaged in the presence of increasing concentrations of fluvastatin. Fluvastatin-resistant replicon containing cells could be generated and proved ∼8-fold less susceptible to fluvastatin than wild-type cultures. The growth efficiency of the resistant replicon containing cells was comparable to that of wild-type replicon cells. The fluvastatin-resistant phenotype was not conferred by mutations in the viral genome but is caused by cellular changes. The resistant cell line had a markedly increased HMG-CoA reductase expression upon statin treatment. Furthermore, the expression of the efflux transporter P-gp was increased in fluvastatin-resistant replicon cells (determined by qRT-PCR and flow cytometry). This increased expression resulted also in an increased functional transport activity as measured by the P-gp mediated efflux of calcein AM. In conclusion, we demonstrate that statin resistance in HCV replicon containing hepatoma cells is conferred by changes in the cellular environment.
[Mh] Termos MeSH primário: Anticolesterolemiantes/farmacologia
Antivirais/farmacologia
Ácidos Graxos Monoinsaturados/farmacologia
Hepacivirus/efeitos dos fármacos
Interações Hospedeiro-Patógeno
Indóis/farmacologia
Replicação Viral/efeitos dos fármacos
[Mh] Termos MeSH secundário: Membro 1 da Subfamília B de Cassetes de Ligação de ATP/agonistas
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo
Linhagem Celular Tumoral
Farmacorresistência Viral
Ativação Enzimática
Regulação da Expressão Gênica
Hepacivirus/genética
Hepacivirus/crescimento & desenvolvimento
Hepatócitos/efeitos dos fármacos
Hepatócitos/patologia
Hepatócitos/virologia
Seres Humanos
Hidroximetilglutaril-CoA-Redutases NADP-Dependentes/genética
Hidroximetilglutaril-CoA-Redutases NADP-Dependentes/metabolismo
Imidazóis/farmacologia
Oligopeptídeos/farmacologia
Replicon
Transdução de Sinais
Proteínas Virais/antagonistas & inibidores
Proteínas Virais/genética
Proteínas Virais/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (ATP-Binding Cassette, Sub-Family B, Member 1); 0 (Anticholesteremic Agents); 0 (Antiviral Agents); 0 (BMS-790052); 0 (Fatty Acids, Monounsaturated); 0 (Imidazoles); 0 (Indoles); 0 (Oligopeptides); 0 (Viral Proteins); 4L066368AS (fluvastatin); 655M5O3W0U (telaprevir); EC 1.1.1.34 (Hydroxymethylglutaryl-CoA-Reductases, NADP-dependent)
[Em] Mês de entrada:1510
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150614
[St] Status:MEDLINE


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[PMID]:26015445
[Au] Autor:Ferrero S; Grados-Torrez RE; Leivar P; Antolín-Llovera M; López-Iglesias C; Cortadellas N; Ferrer JC; Campos N
[Ad] Endereço:Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, 08028 Barcelona, Spain (S.F., P.L., M.A.-L., J.C.F., N.Ca.);Departament de Genètica Molecular, Centre de Recerca en Agrigenòmica (Consejo Superior de Investigaciones Científicas-Institut de Recerca i Tecn
[Ti] Título:Proliferation and Morphogenesis of the Endoplasmic Reticulum Driven by the Membrane Domain of 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase in Plant Cells.
[So] Source:Plant Physiol;168(3):899-914, 2015 Jul.
[Is] ISSN:1532-2548
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) has a key regulatory role in the mevalonate pathway for isoprenoid biosynthesis and is composed of an endoplasmic reticulum (ER)-anchoring membrane domain with low sequence similarity among eukaryotic kingdoms and a conserved cytosolic catalytic domain. Organized smooth endoplasmic reticulum (OSER) structures are common formations of hypertrophied tightly packed ER membranes devoted to specific biosynthetic and secretory functions, the biogenesis of which remains largely unexplored. We show that the membrane domain of plant HMGR suffices to trigger ER proliferation and OSER biogenesis. The proliferating membranes become highly enriched in HMGR protein, but they do not accumulate sterols, indicating a morphogenetic rather than a metabolic role for HMGR. The N-terminal MDVRRRPP motif present in most plant HMGR isoforms is not required for retention in the ER, which was previously proposed, but functions as an ER morphogenic signal. Plant OSER structures are morphologically similar to those of animal cells, emerge from tripartite ER junctions, and mainly build up beside the nuclear envelope, indicating conserved OSER biogenesis in high eukaryotes. Factors other than the OSER-inducing HMGR construct mediate the tight apposition of the proliferating membranes, implying separate ER proliferation and membrane association steps. Overexpression of the membrane domain of Arabidopsis (Arabidopsis thaliana) HMGR leads to ER hypertrophy in every tested cell type and plant species, whereas the knockout of the HMG1 gene from Arabidopsis, encoding its major HMGR isoform, causes ER aggregation at the nuclear envelope. Our results show that the membrane domain of HMGR contributes to ER morphogenesis in plant cells.
[Mh] Termos MeSH primário: Proteínas de Arabidopsis/química
Proteínas de Arabidopsis/metabolismo
Arabidopsis/enzimologia
Retículo Endoplasmático/metabolismo
Hidroximetilglutaril-CoA Redutases/química
Hidroximetilglutaril-CoA Redutases/metabolismo
Hidroximetilglutaril-CoA-Redutases NADP-Dependentes/química
Hidroximetilglutaril-CoA-Redutases NADP-Dependentes/metabolismo
Morfogênese
Células Vegetais/enzimologia
[Mh] Termos MeSH secundário: Motivos de Aminoácidos
Arabidopsis/genética
Arabidopsis/ultraestrutura
Núcleo Celular/metabolismo
Retículo Endoplasmático/ultraestrutura
Genes de Plantas
Proteínas de Fluorescência Verde/metabolismo
Dados de Sequência Molecular
Plantas Geneticamente Modificadas
Estrutura Terciária de Proteína
Esteróis/metabolismo
Relação Estrutura-Atividade
Tabaco/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Arabidopsis Proteins); 0 (Sterols); 147336-22-9 (Green Fluorescent Proteins); EC 1.1.1.- (Hydroxymethylglutaryl CoA Reductases); EC 1.1.1.34 (HMGR protein, Arabidopsis); EC 1.1.1.34 (Hydroxymethylglutaryl-CoA-Reductases, NADP-dependent)
[Em] Mês de entrada:1604
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150528
[St] Status:MEDLINE
[do] DOI:10.1104/pp.15.00597



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