Base de dados : MEDLINE
Pesquisa : D08.811.682.047.820.150.415 [Categoria DeCS]
Referências encontradas : 3744 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 375 ir para página                         

  1 / 3744 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28460556
[Au] Autor:Perani CV; Langgartner D; Uschold-Schmidt N; Füchsl AM; Neumann ID; Reber SO; Slattery DA
[Ad] Endereço:a Department of Behavioural and Molecular Neurobiology , University of Regensburg , Regensburg , Germany.
[Ti] Título:Adrenal gland plasticity in lactating rats and mice is sufficient to maintain basal hypersecretion of corticosterone.
[So] Source:Stress;20(3):303-311, 2017 May.
[Is] ISSN:1607-8888
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Increased basal glucocorticoid secretion and a reduced glucocorticoid response during acute stress, despite only minor changes in the secretion of the major secretagogue adrenocorticotropic hormone (ACTH), have been documented in the peripartum period in several species. We recently showed that the adrenal gland, the site of glucocorticoid synthesis, undergoes substantial postpartum-associated plasticity in the rat at mid-lactation. Here, we asked the question whether adrenal changes already take place around parturition in the rat and in another species, namely the mouse. After demonstrating that several components of the adrenal machinery mediating cholesterol supply for steroidogenesis, including protein levels of hormone-sensitive lipase, low-density lipoprotein receptor (LDLR) and scavenger receptor class-B type-1 (SRB1), are upregulated, while hydroxymethylglutaryl coenzyme A reductase (HMGCR) is downregulated in the lactating rat one day after delivery, as previously observed at mid-lactation, we demonstrated profound changes in the mouse. In detail, protein expression of LDLR, SRB1, HMGCR and adrenal lipid store density were increased in the mouse adrenal one day after parturition as tested via western blot analysis and oil-red lipid staining, respectively. Moreover, using in vitro culture techniques, we observed that isolated adrenal explants from lactating mice secreted higher levels of corticosterone under basal conditions, but showed impaired responsiveness to ACTH, mimicking the in vivo scenario. These results suggest that mechanisms of adaptation in the maternal adrenal after delivery, namely increased cholesterol availability and decreased ACTH sensitivity, are crucial for the basal increase in circulating glucocorticoids and maternal stress hyporesponsiveness that are typical of this period.
[Mh] Termos MeSH primário: Glândulas Suprarrenais/secreção
Corticosterona/secreção
Lactação/metabolismo
[Mh] Termos MeSH secundário: Hormônio Adrenocorticotrópico/metabolismo
Animais
Colesterol/metabolismo
Feminino
Hidroximetilglutaril-CoA Redutases/metabolismo
Camundongos
Fosfoproteínas/metabolismo
Período Pós-Parto/metabolismo
Ratos
Receptores da Corticotropina/metabolismo
Receptores de LDL/metabolismo
Receptores Depuradores Classe B/metabolismo
Esterol Esterase/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Phosphoproteins); 0 (Receptors, Corticotropin); 0 (Receptors, LDL); 0 (Scavenger Receptors, Class B); 0 (steroidogenic acute regulatory protein); 9002-60-2 (Adrenocorticotropic Hormone); 97C5T2UQ7J (Cholesterol); EC 1.1.1.- (Hydroxymethylglutaryl CoA Reductases); EC 3.1.1.13 (Sterol Esterase); W980KJ009P (Corticosterone)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180228
[Lr] Data última revisão:
180228
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE
[do] DOI:10.1080/10253890.2017.1325462


  2 / 3744 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28957322
[Au] Autor:Shu L; Chan KHK; Zhang G; Huan T; Kurt Z; Zhao Y; Codoni V; Trégouët DA; Yang J; Wilson JG; Luo X; Levy D; Lusis AJ; Liu S; Yang X; Cardiogenics Consortium
[Ad] Endereço:Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA, United States of America.
[Ti] Título:Shared genetic regulatory networks for cardiovascular disease and type 2 diabetes in multiple populations of diverse ethnicities in the United States.
[So] Source:PLoS Genet;13(9):e1007040, 2017 Sep.
[Is] ISSN:1553-7404
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Cardiovascular diseases (CVD) and type 2 diabetes (T2D) are closely interrelated complex diseases likely sharing overlapping pathogenesis driven by aberrant activities in gene networks. However, the molecular circuitries underlying the pathogenic commonalities remain poorly understood. We sought to identify the shared gene networks and their key intervening drivers for both CVD and T2D by conducting a comprehensive integrative analysis driven by five multi-ethnic genome-wide association studies (GWAS) for CVD and T2D, expression quantitative trait loci (eQTLs), ENCODE, and tissue-specific gene network models (both co-expression and graphical models) from CVD and T2D relevant tissues. We identified pathways regulating the metabolism of lipids, glucose, and branched-chain amino acids, along with those governing oxidation, extracellular matrix, immune response, and neuronal system as shared pathogenic processes for both diseases. Further, we uncovered 15 key drivers including HMGCR, CAV1, IGF1 and PCOLCE, whose network neighbors collectively account for approximately 35% of known GWAS hits for CVD and 22% for T2D. Finally, we cross-validated the regulatory role of the top key drivers using in vitro siRNA knockdown, in vivo gene knockout, and two Hybrid Mouse Diversity Panels each comprised of >100 strains. Findings from this in-depth assessment of genetic and functional data from multiple human cohorts provide strong support that common sets of tissue-specific molecular networks drive the pathogenesis of both CVD and T2D across ethnicities and help prioritize new therapeutic avenues for both CVD and T2D.
[Mh] Termos MeSH primário: Doenças Cardiovasculares/genética
Diabetes Mellitus Tipo 2/genética
Grupos Étnicos/genética
Redes Reguladoras de Genes
[Mh] Termos MeSH secundário: Adipócitos/metabolismo
Aminoácidos de Cadeia Ramificada/metabolismo
Animais
Caveolina 1/genética
Caveolina 1/metabolismo
Modelos Animais de Doenças
Proteínas da Matriz Extracelular/genética
Proteínas da Matriz Extracelular/metabolismo
Regulação da Expressão Gênica
Estudo de Associação Genômica Ampla
Glucose/metabolismo
Glicoproteínas/genética
Glicoproteínas/metabolismo
Seres Humanos
Hidroximetilglutaril-CoA Redutases/genética
Hidroximetilglutaril-CoA Redutases/metabolismo
Fator de Crescimento Insulin-Like I/genética
Fator de Crescimento Insulin-Like I/metabolismo
Metabolismo dos Lipídeos
Masculino
Camundongos
Polimorfismo de Nucleotídeo Único
Locos de Características Quantitativas
Reprodutibilidade dos Testes
Estados Unidos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amino Acids, Branched-Chain); 0 (Cav1 protein, mouse); 0 (Caveolin 1); 0 (Extracellular Matrix Proteins); 0 (Glycoproteins); 0 (Pcolce protein, mouse); 0 (insulin-like growth factor-1, mouse); 67763-96-6 (Insulin-Like Growth Factor I); EC 1.1.1.- (Hydroxymethylglutaryl CoA Reductases); IY9XDZ35W2 (Glucose)
[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:170929
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pgen.1007040


  3 / 3744 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo SciELO Brasil
[PMID]:28902926
[Au] Autor:Guo N; Zhang N; Yan L; Cao X; Lv F; Wang J; Wang Y; Cong H
[Ad] Endereço:Department of Cardiology, Tianjin Chest Hospital, Tianjin Medical University, Tianjin, China.
[Ti] Título:Down-regulation of single-stranded DNA-binding protein 1 expression induced by HCMV infection promotes lipid accumulation in cells.
[So] Source:Braz J Med Biol Res;50(11):e6389, 2017 Sep 12.
[Is] ISSN:1414-431X
[Cp] País de publicação:Brazil
[La] Idioma:eng
[Ab] Resumo:The objective of this study was to observe the infection of human cytomegalovirus (HCMV) to human umbilical vein endothelial cells, and its effect on the expression of single-stranded DNA-binding protein (SSBP1) and on lipid metabolism in endothelial cells. We screened the differential expression of mRNAs after HCMV infection by suppression subtractive hybridization and the expression levels of SSBP1 mRNA and protein after HCMV infection by real-time PCR and western blot. After verification of successful infection by indirect immunofluorescent staining and RT-PCR, we found a differential expression of lipid metabolism-related genes including LDLR, SCARB, CETP, HMGCR, ApoB and LPL induced by HCMV infection. The expression levels of SSBP1 mRNA and protein after HCMV infection were significantly down-regulated. Furthermore, we found that upregulation of SSBP1 inhibited the expression of atherosclerosis-associated LDLR, SCARB, HMGCR, CETP as well as the accumulation of lipids in the cells. The results showed that the inhibition of SSBP1 by HCMV infection promotes lipid accumulation in the cells.
[Mh] Termos MeSH primário: Infecções por Citomegalovirus/metabolismo
Proteínas de Ligação a DNA/metabolismo
Células Endoteliais da Veia Umbilical Humana/metabolismo
Células Endoteliais da Veia Umbilical Humana/virologia
Metabolismo dos Lipídeos/fisiologia
Proteínas Mitocondriais/metabolismo
[Mh] Termos MeSH secundário: Aterosclerose/metabolismo
Aterosclerose/virologia
Colesterol/análise
Proteínas de Transferência de Ésteres de Colesterol/metabolismo
Proteínas de Ligação a DNA/genética
Regulação para Baixo
Seres Humanos
Hidroximetilglutaril-CoA Redutases/metabolismo
Metabolismo dos Lipídeos/genética
Proteínas Mitocondriais/genética
Receptores de LDL/metabolismo
Receptores Depuradores Classe B/metabolismo
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (CETP protein, human); 0 (Cholesterol Ester Transfer Proteins); 0 (DNA-Binding Proteins); 0 (LDLR protein, human); 0 (Mitochondrial Proteins); 0 (Receptors, LDL); 0 (SCARB1 protein, human); 0 (SSBP1 protein, human); 0 (Scavenger Receptors, Class B); 97C5T2UQ7J (Cholesterol); EC 1.1.1.- (HMGCR protein, human); EC 1.1.1.- (Hydroxymethylglutaryl CoA Reductases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171006
[Lr] Data última revisão:
171006
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170914
[St] Status:MEDLINE


  4 / 3744 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28882874
[Au] Autor:Loregger A; Raaben M; Tan J; Scheij S; Moeton M; van den Berg M; Gelberg-Etel H; Stickel E; Roitelman J; Brummelkamp T; Zelcer N
[Ad] Endereço:From the Department of Medical Biochemistry, Academic Medical Center of the University of Amsterdam, The Netherlands (A.L., J.T., S.S., M.M., M.v.d.B., N.Z.); Division of Biochemistry, The Netherlands Cancer Institute, Amsterdam (M.R., E.S., T.B.); CeMM Research Center for Molecular Medicine of the
[Ti] Título:Haploid Mammalian Genetic Screen Identifies UBXD8 as a Key Determinant of HMGCR Degradation and Cholesterol Biosynthesis.
[So] Source:Arterioscler Thromb Vasc Biol;37(11):2064-2074, 2017 Nov.
[Is] ISSN:1524-4636
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: The cellular demand for cholesterol requires control of its biosynthesis by the mevalonate pathway. Regulation of HMGCR (3-hydroxy-3-methylglutaryl coenzyme A reductase), a rate-limiting enzyme in this pathway and the target of statins, is a key control point herein. Accordingly, HMGCR is subject to negative and positive regulation. In particular, the ability of oxysterols and intermediates of the mevalonate pathway to stimulate its proteasomal degradation is an exquisite example of metabolically controlled feedback regulation. To define the genetic determinants that govern this process, we conducted an unbiased haploid mammalian genetic screen. APPROACH AND RESULTS: We generated human haploid cells with mNeon fused to endogenous HMGCR using CRISPR/Cas9 and used these cells to interrogate regulation of HMGCR abundance in live cells. This resulted in identification of known and new regulators of HMGCR, and among the latter, UBXD8 (ubiquitin regulatory X domain-containing protein 8), a gene that has not been previously implicated in this process. We demonstrate that UBXD8 is an essential determinant of metabolically stimulated degradation of HMGCR and of cholesterol biosynthesis in multiple cell types. Accordingly, UBXD8 ablation leads to aberrant cholesterol synthesis due to loss of feedback control. Mechanistically, we show that UBXD8 is necessary for sterol-stimulated dislocation of ubiquitylated HMGCR from the endoplasmic reticulum membrane en route to proteasomal degradation, a function dependent on its UBX domain. CONCLUSIONS: We establish UBXD8 as a previously unrecognized determinant that couples flux across the mevalonate pathway to control of cholesterol synthesis and demonstrate the feasibility of applying mammalian haploid genetics to study metabolic traits.
[Mh] Termos MeSH primário: Proteínas Sanguíneas/metabolismo
Colesterol/biossíntese
Haploidia
Hidroximetilglutaril-CoA Redutases/metabolismo
Proteínas de Membrana/metabolismo
[Mh] Termos MeSH secundário: Animais
Proteínas Sanguíneas/genética
Sistemas CRISPR-Cas
Retículo Endoplasmático/enzimologia
Estabilidade Enzimática
Retroalimentação Fisiológica
Regulação Enzimológica da Expressão Gênica
Células Hep G2
Hepatócitos/enzimologia
Seres Humanos
Hidroximetilglutaril-CoA Redutases/genética
Proteínas de Membrana/genética
Ácido Mevalônico/metabolismo
Microscopia Confocal
Complexo de Endopeptidases do Proteassoma/metabolismo
Transporte Proteico
Proteólise
Ratos
Proteínas Recombinantes de Fusão/metabolismo
Transfecção
Ubiquitinação
[Pt] Tipo de publicação:JOURNAL ARTICLE; VIDEO-AUDIO MEDIA
[Nm] Nome de substância:
0 (Blood Proteins); 0 (ETEA protein, human); 0 (Membrane Proteins); 0 (Recombinant Fusion Proteins); 97C5T2UQ7J (Cholesterol); EC 1.1.1.- (HMGCR protein, human); EC 1.1.1.- (Hydroxymethylglutaryl CoA Reductases); EC 3.4.25.1 (Proteasome Endopeptidase Complex); S5UOB36OCZ (Mevalonic Acid)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171123
[Lr] Data última revisão:
171123
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170909
[St] Status:MEDLINE
[do] DOI:10.1161/ATVBAHA.117.310002


  5 / 3744 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28846118
[Au] Autor:Ference BA; Kastelein JJP; Ginsberg HN; Chapman MJ; Nicholls SJ; Ray KK; Packard CJ; Laufs U; Brook RD; Oliver-Williams C; Butterworth AS; Danesh J; Smith GD; Catapano AL; Sabatine MS
[Ad] Endereço:Division of Cardiovascular Medicine, Wayne State University School of Medicine, Detroit, Michigan.
[Ti] Título:Association of Genetic Variants Related to CETP Inhibitors and Statins With Lipoprotein Levels and Cardiovascular Risk.
[So] Source:JAMA;318(10):947-956, 2017 09 12.
[Is] ISSN:1538-3598
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Importance: Some cholesteryl ester transfer protein (CETP) inhibitors lower low-density lipoprotein cholesterol (LDL-C) levels without reducing cardiovascular events, suggesting that the clinical benefit of lowering LDL-C may depend on how LDL-C is lowered. Objective: To estimate the association between changes in levels of LDL-C (and other lipoproteins) and the risk of cardiovascular events related to variants in the CETP gene, both alone and in combination with variants in the 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) gene. Design, Setting, and Participants: Mendelian randomization analyses evaluating the association between CETP and HMGCR scores, changes in lipid and lipoprotein levels, and the risk of cardiovascular events involving 102 837 participants from 14 cohort or case-control studies conducted in North America or the United Kingdom between 1948 and 2012. The associations with cardiovascular events were externally validated in 189 539 participants from 48 studies conducted between 2011 and 2015. Exposures: Differences in mean high-density lipoprotein cholesterol (HDL-C), LDL-C, and apolipoprotein B (apoB) levels in participants with CETP scores at or above vs below the median. Main Outcomes and Measures: Odds ratio (OR) for major cardiovascular events. Results: The primary analysis included 102 837 participants (mean age, 59.9 years; 58% women) who experienced 13 821 major cardiovascular events. The validation analyses included 189 539 participants (mean age, 58.5 years; 39% women) with 62 240 cases of coronary heart disease (CHD). Considered alone, the CETP score was associated with higher levels of HDL-C, lower LDL-C, concordantly lower apoB, and a corresponding lower risk of major vascular events (OR, 0.946 [95% CI, 0.921-0.972]) that was similar in magnitude to the association between the HMGCR score and risk of major cardiovascular events per unit change in levels of LDL-C (and apoB). When combined with the HMGCR score, the CETP score was associated with the same reduction in LDL-C levels but an attenuated reduction in apoB levels and a corresponding attenuated nonsignificant risk of major cardiovascular events (OR, 0.985 [95% CI, 0.955-1.015]). In external validation analyses, a genetic score consisting of variants with naturally occurring discordance between levels of LDL-C and apoB was associated with a similar risk of CHD per unit change in apoB level (OR, 0.782 [95% CI, 0.720-0.845] vs 0.793 [95% CI, 0.774-0.812]; P = .79 for difference), but a significantly attenuated risk of CHD per unit change in LDL-C level (OR, 0.916 [95% CI, 0.890-0.943] vs 0.831 [95% CI, 0.816-0.847]; P < .001) compared with a genetic score associated with concordant changes in levels of LDL-C and apoB. Conclusions and Relevance: Combined exposure to variants in the genes that encode the targets of CETP inhibitors and statins was associated with discordant reductions in LDL-C and apoB levels and a corresponding risk of cardiovascular events that was proportional to the attenuated reduction in apoB but significantly less than expected per unit change in LDL-C. The clinical benefit of lowering LDL-C levels may therefore depend on the corresponding reduction in apoB-containing lipoprotein particles.
[Mh] Termos MeSH primário: Apolipoproteínas B/sangue
Doenças Cardiovasculares/genética
Proteínas de Transferência de Ésteres de Colesterol/antagonistas & inibidores
LDL-Colesterol/sangue
Variação Genética
Hidroximetilglutaril-CoA Redutases/genética
Hipercolesterolemia/genética
[Mh] Termos MeSH secundário: Anticolesterolemiantes/uso terapêutico
Doenças Cardiovasculares/prevenção & controle
Proteínas de Transferência de Ésteres de Colesterol/genética
HDL-Colesterol/sangue
Feminino
Seres Humanos
Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico
Hipercolesterolemia/sangue
Hipercolesterolemia/tratamento farmacológico
Masculino
Análise da Randomização Mendeliana
Meia-Idade
Fatores de Risco
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anticholesteremic Agents); 0 (Apolipoproteins B); 0 (CETP protein, human); 0 (Cholesterol Ester Transfer Proteins); 0 (Cholesterol, HDL); 0 (Cholesterol, LDL); 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors); EC 1.1.1.- (HMGCR protein, human); EC 1.1.1.- (Hydroxymethylglutaryl CoA Reductases)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170922
[Lr] Data última revisão:
170922
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170829
[St] Status:MEDLINE
[do] DOI:10.1001/jama.2017.11467


  6 / 3744 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28845666
[Au] Autor:Paramasivan K; Mutturi S
[Ad] Endereço:Microbiology and Fermentation Technology Department, CSIR-Central Food Technological Research Institute , Mysore, India.
[Ti] Título:Regeneration of NADPH Coupled with HMG-CoA Reductase Activity Increases Squalene Synthesis in Saccharomyces cerevisiae.
[So] Source:J Agric Food Chem;65(37):8162-8170, 2017 Sep 20.
[Is] ISSN:1520-5118
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Although overexpression of the tHMG1 gene is a well-known strategy for terpene synthesis in Saccharomyces cerevisiae, the optimal level for tHMG1p has not been established. In the present study, it was observed that two copies of the tHMG1 gene on a dual gene expression cassette improved squalene synthesis in laboratory strain by 16.8-fold in comparison to single-copy expression. It was also observed that tHMG1p is limited by its cofactor (NADPH), as the overexpression of NADPH regenerating genes', viz., ZWF1 and POS5 (full length and without mitochondrial presequence), has led to its increased enzyme activity. Further, it was demonstrated that overexpression of full-length POS5 has improved squalene synthesis in cytosol. Finally, when tHMG1 and full-length POS5 were co-overexpressed there was a net 27.5-fold increase in squalene when compared to control strain. These results suggest novel strategies to increase squalene accumulation in S. cerevisiae.
[Mh] Termos MeSH primário: Acil Coenzima A/metabolismo
Hidroximetilglutaril-CoA Redutases/metabolismo
NADP/metabolismo
Proteínas de Saccharomyces cerevisiae/metabolismo
Saccharomyces cerevisiae/metabolismo
Esqualeno/metabolismo
[Mh] Termos MeSH secundário: Acil Coenzima A/genética
Hidroximetilglutaril-CoA Redutases/genética
Proteínas Mitocondriais/genética
Proteínas Mitocondriais/metabolismo
Fosfotransferases (Aceptor do Grupo Álcool)/genética
Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo
Saccharomyces cerevisiae/enzimologia
Saccharomyces cerevisiae/genética
Proteínas de Saccharomyces cerevisiae/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Acyl Coenzyme A); 0 (Mitochondrial Proteins); 0 (Saccharomyces cerevisiae Proteins); 1553-55-5 (3-hydroxy-3-methylglutaryl-coenzyme A); 53-59-8 (NADP); 7QWM220FJH (Squalene); EC 1.1.1.- (Hydroxymethylglutaryl CoA Reductases); EC 2.7.1.- (Phosphotransferases (Alcohol Group Acceptor)); EC 2.7.1.86 (POS5 protein, S cerevisiae)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171113
[Lr] Data última revisão:
171113
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170829
[St] Status:MEDLINE
[do] DOI:10.1021/acs.jafc.7b02945


  7 / 3744 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28795592
[Au] Autor:Zaher NH; Rashed ER; El-Ghazaly MA
[Ad] Endereço:Department of Drug Radiation Research, National Center for Radiation Research & Technology, Technology (NCRRT), Egyptian Atomic Energy Authority (EAEA), PO box 29, Nasr City, Cairo, Egypt.
[Ti] Título:Semi-synthetic thymoquinone analogs: new prototypes as potential antihyperlipidemics in irradiated rats.
[So] Source:Future Med Chem;9(13):1483-1493, 2017 Sep.
[Is] ISSN:1756-8927
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:AIM: Thymoquinone (TQ), has been reported to possess strong antihyperlipidemic properties. However, a variety of serious side effects has been reported for TQ. The present study aimed to evaluate the potential antihyperlipidemic activity of newly synthesized TQ analogs. METHODS & RESULTS: first, novel TQ derivatives were studied against radiation-induced dyslipidemia in male rats. Second, the most promising sulfur derivatives (4-7), were further tested to elucidate their possible mechanism(s) of actions. Results showed that they possess Hydroxymethyl Glutaryl-Co A reductase inhibitory activity, as well as stimulatory effects on the activities of each of plasma Lecithin-Cholesterol Acyltransferase and lipoprotein lipase enzymes. CONCLUSION: TQ derivatives (4-7), could be considered as promising agents in pathologies implicating impaired lipid metabolism, preclinical evaluation is warranted. [Formula: see text].
[Mh] Termos MeSH primário: Benzoquinonas/química
Hidroximetilglutaril-CoA Redutases/metabolismo
Hipolipemiantes/síntese química
[Mh] Termos MeSH secundário: Animais
Benzoquinonas/metabolismo
Benzoquinonas/uso terapêutico
Dislipidemias/tratamento farmacológico
Dislipidemias/etiologia
Dislipidemias/veterinária
Raios gama
Hidroximetilglutaril-CoA Redutases/sangue
Hidroximetilglutaril-CoA Redutases/química
Hipolipemiantes/farmacologia
Hipolipemiantes/uso terapêutico
Metabolismo dos Lipídeos/efeitos dos fármacos
Lipídeos/sangue
Lipase Lipoproteica/antagonistas & inibidores
Lipase Lipoproteica/metabolismo
Fígado/efeitos dos fármacos
Fígado/enzimologia
Fígado/efeitos da radiação
Masculino
Fosfatidilcolina-Esterol O-Aciltransferase/antagonistas & inibidores
Fosfatidilcolina-Esterol O-Aciltransferase/metabolismo
Ratos
Ratos Wistar
Irradiação Corporal Total/efeitos adversos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Benzoquinones); 0 (Hypolipidemic Agents); 0 (Lipids); 490-91-5 (thymoquinone); EC 1.1.1.- (Hydroxymethylglutaryl CoA Reductases); EC 2.3.1.43 (Phosphatidylcholine-Sterol O-Acyltransferase); EC 3.1.1.34 (Lipoprotein Lipase)
[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:170811
[St] Status:MEDLINE
[do] DOI:10.4155/fmc-2017-0054


  8 / 3744 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28720842
[Au] Autor:Smith A; Murphy L; Zgaga L; Barron TI; Bennett K
[Ad] Endereço:Department of Pharmacology and Therapeutics, Trinity Centre for Health Sciences, Trinity College, University of Dublin, Dublin D08 W9RT, Ireland.
[Ti] Título:Pre-diagnostic statin use, lymph node status and mortality in women with stages I-III breast cancer.
[So] Source:Br J Cancer;117(4):588-596, 2017 Aug 08.
[Is] ISSN:1532-1827
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Recent meta-analyses suggest that pre-diagnostic statin use is associated with reduced breast cancer-specific mortality. Studies have shown that high breast tumour expression of the statin target (3-hydroxy-3-methylglutaryl coenzyme-A reductase) is associated with lymph-node negative cancer. Therefore, we examined the association between pre-diagnostic statin use and; lymph node status, breast cancer-specific and all-cause mortality. METHODS: Women with stages I-III breast cancer were identified from the National Cancer Registry of Ireland (N=6314). Pre-diagnostic statin users were identified from linked prescription claims data (N=2082). Relative risks were estimated for associations between pre-diagnostic statin use and lymph node status. Hazard ratios (HR) were estimated for associations between pre-diagnostic statin use and breast cancer-specific and all-cause mortality. RESULTS: Pre-diagnostic statin use was not associated with lymph node negative status at diagnosis. In multivariate analyses, pre-diagnostic statin use was associated with reduced all-cause (HR 0.78 95% confidence interval (CI) 0.69, 0.89) and breast cancer-specific mortality (HR 0.81 95% CI 0.68, 0.96). This reduction in cancer-specific mortality was greatest in statin-users with oestrogen (ER) receptor-positive tumours (HR 0.69 95% CI 0.55, 0.85). CONCLUSION: Patients with pre-diagnostic statin exposure had a significant reduction in breast cancer-specific mortality, which was even more pronounced in women with ER+ tumours.
[Mh] Termos MeSH primário: Neoplasias da Mama/mortalidade
Neoplasias da Mama/patologia
Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico
Linfonodos/patologia
[Mh] Termos MeSH secundário: Idoso
Neoplasias da Mama/química
Neoplasias da Mama/diagnóstico
Causas de Morte
Feminino
Seres Humanos
Hidroximetilglutaril-CoA Redutases
Irlanda/epidemiologia
Metástase Linfática
Meia-Idade
Estadiamento de Neoplasias
Receptores Estrogênicos/análise
Sistema de Registros
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors); 0 (Receptors, Estrogen); EC 1.1.1.- (Hydroxymethylglutaryl CoA Reductases)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170907
[Lr] Data última revisão:
170907
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170720
[St] Status:MEDLINE
[do] DOI:10.1038/bjc.2017.227


  9 / 3744 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28686747
[Au] Autor:Quintana AM; Hernandez JA; Gonzalez CG
[Ad] Endereço:Department of Biological Sciences, University of Texas El Paso, El Paso, TX, United States of America.
[Ti] Título:Functional analysis of the zebrafish ortholog of HMGCS1 reveals independent functions for cholesterol and isoprenoids in craniofacial development.
[So] Source:PLoS One;12(7):e0180856, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:There are 8 different human syndromes caused by mutations in the cholesterol synthesis pathway. A subset of these disorders such as Smith-Lemli-Opitz disorder, are associated with facial dysmorphia. However, the molecular and cellular mechanisms underlying such facial deficits are not fully understood, primarily because of the diverse functions associated with the cholesterol synthesis pathway. Recent evidence has demonstrated that mutation of the zebrafish ortholog of HMGCR results in orofacial clefts. Here we sought to expand upon these data, by deciphering the cholesterol dependent functions of the cholesterol synthesis pathway from the cholesterol independent functions. Moreover, we utilized loss of function analysis and pharmacological inhibition to determine the extent of sonic hedgehog (Shh) signaling in animals with aberrant cholesterol and/or isoprenoid synthesis. Our analysis confirmed that mutation of hmgcs1, which encodes the first enzyme in the cholesterol synthesis pathway, results in craniofacial abnormalities via defects in cranial neural crest cell differentiation. Furthermore targeted pharmacological inhibition of the cholesterol synthesis pathway revealed a novel function for isoprenoid synthesis during vertebrate craniofacial development. Mutation of hmgcs1 had no effect on Shh signaling at 2 and 3 days post fertilization (dpf), but did result in a decrease in the expression of gli1, a known Shh target gene, at 4 dpf, after morphological deficits in craniofacial development and chondrocyte differentiation were observed in hmgcs1 mutants. These data raise the possibility that deficiencies in cholesterol modulate chondrocyte differentiation by a combination of Shh independent and Shh dependent mechanisms. Moreover, our results describe a novel function for isoprenoids in facial development and collectively suggest that cholesterol regulates craniofacial development through versatile mechanisms.
[Mh] Termos MeSH primário: Colesterol/biossíntese
Anormalidades Craniofaciais/genética
Proteínas Hedgehog/genética
Hidroximetilglutaril-CoA Redutases/genética
Hidroximetilglutaril-CoA Sintase/genética
Terpenos/metabolismo
Proteínas de Peixe-Zebra/genética
Proteína GLI1 em Dedos de Zinco/genética
[Mh] Termos MeSH secundário: Animais
Anticolesterolemiantes/farmacologia
Atorvastatina Cálcica/farmacologia
Benzofenonas/farmacologia
Padronização Corporal/efeitos dos fármacos
Padronização Corporal/genética
Diferenciação Celular/efeitos dos fármacos
Condrócitos/efeitos dos fármacos
Condrócitos/metabolismo
Condrócitos/patologia
Anormalidades Craniofaciais/metabolismo
Anormalidades Craniofaciais/patologia
Embrião não Mamífero
Inibidores Enzimáticos/farmacologia
Regulação da Expressão Gênica no Desenvolvimento
Proteínas Hedgehog/metabolismo
Seres Humanos
Hidroximetilglutaril-CoA Redutases/metabolismo
Hidroximetilglutaril-CoA Sintase/metabolismo
Crista Neural/efeitos dos fármacos
Crista Neural/metabolismo
Crista Neural/patologia
Piperidinas/farmacologia
Piridinas/farmacologia
Transdução de Sinais
Terpenos/antagonistas & inibidores
Peixe-Zebra
Proteínas de Peixe-Zebra/metabolismo
Proteína GLI1 em Dedos de Zinco/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anticholesteremic Agents); 0 (Benzophenones); 0 (Enzyme Inhibitors); 0 (Hedgehog Proteins); 0 (Piperidines); 0 (Pyridines); 0 (Shha protein, zebrafish); 0 (Terpenes); 0 (Zebrafish Proteins); 0 (Zinc Finger Protein GLI1); 161582-11-2 (Ro 48-8071); 48A5M73Z4Q (Atorvastatin Calcium); 97C5T2UQ7J (Cholesterol); EC 1.1.1.- (Hydroxymethylglutaryl CoA Reductases); EC 2.3.3.10 (HMGCS1 protein, human); EC 2.3.3.10 (Hydroxymethylglutaryl-CoA Synthase); IOW153004F (lonafarnib)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170922
[Lr] Data última revisão:
170922
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170708
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0180856


  10 / 3744 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28672048
[Au] Autor:Omar I; Rom O; Aviram M; Cohen-Daniel L; Gebre AK; Parks JS; Berger M
[Ad] Endereço:The Lautenberg Centre for Immunology and Cancer Research, The Biomedical Research Institute Israel Canada of the Faculty of Medicine, The Hebrew University Hadassah Medical School Jerusalem, Jerusalem, Israel.
[Ti] Título:Slfn2 mutation-induced loss of T-cell quiescence leads to elevated de novo sterol synthesis.
[So] Source:Immunology;152(3):484-493, 2017 Nov.
[Is] ISSN:1365-2567
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Acquisition of a 'quiescence programme' by naive T cells is important to provide a stress-free environment and resistance to apoptosis while preserving their responsiveness to activating stimuli. Therefore, the survival and proper function of naive T cells depends on their ability to maintain quiescence. Recently we demonstrated that by preventing chronic unresolved endoplasmic reticulum (ER) stress, Schlafen2 (Slfn2) maintains a stress-free environment to conserve a pool of naive T cells ready to respond to a microbial invasion. These findings strongly suggest an intimate association between quiescence and stress signalling. However, the connection between ER stress conditions and loss of T-cell quiescence is unknown. Here we demonstrate that homeostasis of cholesterol and lipids, is disrupted in T cells and monocytes from Slfn2-mutant, elektra, mice with higher levels of lipid rafts and lipid droplets found in these cells. Moreover, elektra T cells had elevated levels of free cholesterol and cholesteryl ester due to increased de novo synthesis and higher levels of the enzyme HMG-CoA reductase. As cholesterol plays an important role in the transition of T cells from resting to active state, and ER regulates cholesterol and lipid synthesis, we suggest that regulation of cholesterol levels through the prevention of ER stress is an essential component of the mechanism by which Slfn2 regulates quiescence.
[Mh] Termos MeSH primário: Proteínas de Ciclo Celular/metabolismo
Proliferação Celular
Senescência Celular
Colesterol/biossíntese
Ativação Linfocitária
Mutação
Linfócitos T/metabolismo
[Mh] Termos MeSH secundário: Animais
Proteínas de Ciclo Celular/genética
Ésteres do Colesterol/biossíntese
Estresse do Retículo Endoplasmático
Genótipo
Hidroximetilglutaril-CoA Redutases/metabolismo
Gotículas Lipídicas/metabolismo
Microdomínios da Membrana/metabolismo
Camundongos Endogâmicos C57BL
Camundongos Mutantes
Monócitos/imunologia
Monócitos/metabolismo
Fenótipo
Linfócitos T/imunologia
Regulação para Cima
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cell Cycle Proteins); 0 (Cholesterol Esters); 0 (schlafen-2 protein, mouse); 97C5T2UQ7J (Cholesterol); EC 1.1.1.- (Hydroxymethylglutaryl CoA Reductases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170704
[St] Status:MEDLINE
[do] DOI:10.1111/imm.12785



página 1 de 375 ir para página                         
   


Refinar a pesquisa
  Base de dados : MEDLINE Formulário avançado   

    Pesquisar no campo  
1  
2
3
 
           



Search engine: iAH v2.6 powered by WWWISIS

BIREME/OPAS/OMS - Centro Latino-Americano e do Caribe de Informação em Ciências da Saúde