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Pesquisa : D04.210.500.105.225.130.330 [Categoria DeCS]
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  1 / 201 MEDLINE  
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[PMID]:28423182
[Au] Autor:Hwang E; Cheong HK; Kim SY; Kwon O; Blain KY; Choe S; Yeo KJ; Jung YW; Jeon YH; Cheong C
[Ad] Endereço:Division of Bioconvergence Analysis, Korea Basic Science Institute (KBSI), Chungbuk, Korea.
[Ti] Título:Crystal structure of the EnvZ periplasmic domain with CHAPS.
[So] Source:FEBS Lett;591(10):1419-1428, 2017 May.
[Is] ISSN:1873-3468
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Bacteria sense and respond to osmolarity through the EnvZ-OmpR two-component system. The structure of the periplasmic sensor domain of EnvZ (EnvZ-PD) is not available yet. Here, we present the crystal structure of EnvZ-PD in the presence of CHAPS detergent. The structure of EnvZ-PD shows similar folding topology to the PDC domains of PhoQ, DcuS, and CitA, but distinct orientations of helices and ß-hairpin structures. The CD and NMR spectra of EnvZ-PD in the presence of cholate, a major component of bile salts, are similar to those with CHAPS. Chemical cross-linking shows that the dimerization of EnvZ-PD is significantly inhibited by the CHAPS and cholate. Together with ß-galactosidase assay, these results suggest that bile salts may affect the EnvZ structure and function in Escherichia coli.
[Mh] Termos MeSH primário: Proteínas da Membrana Bacteriana Externa/química
Colatos/farmacologia
Ácidos Cólicos/farmacologia
Detergentes/farmacologia
Proteínas de Escherichia coli/química
Escherichia coli/metabolismo
Complexos Multienzimáticos/química
[Mh] Termos MeSH secundário: Proteínas da Membrana Bacteriana Externa/efeitos dos fármacos
Dicroísmo Circular
Cristalografia por Raios X
Proteínas de Escherichia coli/efeitos dos fármacos
Modelos Moleculares
Complexos Multienzimáticos/efeitos dos fármacos
Domínios Proteicos/efeitos dos fármacos
Dobramento de Proteína/efeitos dos fármacos
Estrutura Secundária de Proteína/efeitos dos fármacos
[Pt] Tipo de publicação:LETTER
[Nm] Nome de substância:
0 (Bacterial Outer Membrane Proteins); 0 (Cholates); 0 (Cholic Acids); 0 (Detergents); 0 (Escherichia coli Proteins); 0 (Multienzyme Complexes); EC 2.7.3.- (envZ protein, E coli); QBP25342AG (3-((3-cholamidopropyl)dimethylammonium)-1-propanesulfonate)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170919
[Lr] Data última revisão:
170919
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170420
[St] Status:MEDLINE
[do] DOI:10.1002/1873-3468.12658


  2 / 201 MEDLINE  
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[PMID]:28088462
[Au] Autor:Asai Y; Yamada T; Tsukita S; Takahashi K; Maekawa M; Honma M; Ikeda M; Murakami K; Munakata Y; Shirai Y; Kodama S; Sugisawa T; Chiba Y; Kondo Y; Kaneko K; Uno K; Sawada S; Imai J; Nakamura Y; Yamaguchi H; Tanaka K; Sasano H; Mano N; Ueno Y; Shimosegawa T; Katagiri H
[Ad] Endereço:Department of Metabolism and Diabetes, Tohoku University Graduate School of Medicine, Sendai, Japan.
[Ti] Título:Activation of the Hypoxia Inducible Factor 1α Subunit Pathway in Steatotic Liver Contributes to Formation of Cholesterol Gallstones.
[So] Source:Gastroenterology;152(6):1521-1535.e8, 2017 May.
[Is] ISSN:1528-0012
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND & AIMS: Hypoxia-inducible factor 1α subunit (HIF1A) is a transcription factor that controls the cellular response to hypoxia and is activated in hepatocytes of patients with nonalcoholic fatty liver disease (NAFLD). NAFLD increases the risk for cholesterol gallstone disease by unclear mechanisms. We studied the relationship between HIF1A and gallstone formation associated with liver steatosis. METHODS: We performed studies with mice with inducible disruption of Hif1a in hepatocytes via a Cre adenoviral vector (inducible hepatocyte-selective HIF1A knockout [iH-HIFKO] mice), and mice without disruption of Hif1a (control mice). Mice were fed a diet rich in cholesterol and cholate for 1 or 2 weeks; gallbladders were collected and the number of gallstones was determined. Livers and biliary tissues were analyzed by histology, quantitative reverse-transcription polymerase chain reaction, immunohistochemistry, and immunoblots. We measured concentrations of bile acid, cholesterol, and phospholipid in bile and rates of bile flow. Primary hepatocytes and cholangiocytes were isolated and analyzed. HIF1A was knocked down in Hepa1-6 cells with small interfering RNAs. Liver biopsy samples from patients with NAFLD, with or without gallstones, were analyzed by quantitative reverse-transcription polymerase chain reaction. RESULTS: Control mice fed a diet rich in cholesterol and cholate developed liver steatosis with hypoxia; levels of HIF1A protein were increased in hepatocytes around central veins and 90% of mice developed cholesterol gallstones. Only 20% of the iH-HIFKO mice developed cholesterol gallstones. In iH-HIFKO mice, the biliary lipid concentration was reduced by 36%, compared with control mice, and bile flow was increased by 35%. We observed increased water secretion from hepatocytes into bile canaliculi to mediate these effects, resulting in suppression of cholelithogenesis. Hepatic expression of aquaporin 8 (AQP8) protein was 1.5-fold higher in iH-HIFKO mice than in control mice. Under hypoxic conditions, cultured hepatocytes increased expression of Hif1a, Hmox1, and Vegfa messenger RNAs (mRNAs), and down-regulated expression of AQP8 mRNA and protein; AQP8 down-regulation was not observed in cells with knockdown of HIF1A. iH-HIFKO mice had reduced inflammation and mucin deposition in the gallbladder compared with control mice. Liver tissues from patients with NAFLD with gallstones had increased levels of HIF1A, HMOX1, and VEGFA mRNAs, compared with livers from patients with NAFLD without gallstones. CONCLUSIONS: In steatotic livers of mice, hypoxia up-regulates expression of HIF1A, which reduces expression of AQP8 and concentrates biliary lipids via suppression of water secretion from hepatocytes. This promotes cholesterol gallstone formation. Livers from patients with NAFLD and gallstones express higher levels of HIF1A than livers from patients with NAFLD without gallstones.
[Mh] Termos MeSH primário: Colesterol/metabolismo
Cálculos Biliares/genética
Cálculos Biliares/metabolismo
Subunidade alfa do Fator 1 Induzível por Hipóxia/genética
Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo
Hepatopatia Gordurosa não Alcoólica/metabolismo
[Mh] Termos MeSH secundário: Animais
Aquaporinas/genética
Aquaporinas/metabolismo
Bile/metabolismo
Ácidos e Sais Biliares/metabolismo
Colatos/administração & dosagem
Colesterol na Dieta/administração & dosagem
Colesterol na Dieta/metabolismo
Regulação para Baixo/genética
Feminino
Vesícula Biliar/patologia
Cálculos Biliares/patologia
Heme Oxigenase-1/genética
Hepatócitos/metabolismo
Seres Humanos
Hipóxia/metabolismo
Inflamação/etiologia
Fígado/metabolismo
Masculino
Proteínas de Membrana/genética
Camundongos
Camundongos Knockout
Mucinas/metabolismo
Hepatopatia Gordurosa não Alcoólica/complicações
RNA Mensageiro/metabolismo
Transdução de Sinais
Fator A de Crescimento do Endotélio Vascular/genética
Água/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Aquaporins); 0 (Bile Acids and Salts); 0 (Cholates); 0 (Cholesterol, Dietary); 0 (Hif1a protein, mouse); 0 (Hypoxia-Inducible Factor 1, alpha Subunit); 0 (Membrane Proteins); 0 (Mucins); 0 (RNA, Messenger); 0 (Vascular Endothelial Growth Factor A); 0 (aquaporin 8); 0 (vascular endothelial growth factor A, mouse); 059QF0KO0R (Water); 97C5T2UQ7J (Cholesterol); EC 1.14.14.18 (Heme Oxygenase-1); EC 1.14.14.18 (Hmox1 protein, mouse)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170808
[Lr] Data última revisão:
170808
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170116
[St] Status:MEDLINE


  3 / 201 MEDLINE  
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[PMID]:27648822
[Au] Autor:Yücel O; Drees S; Jagmann N; Patschkowski T; Philipp B
[Ad] Endereço:Westfälische Wilhelms-Universität Münster Institut für Molekulare Mikrobiologie und Biotechnologie, Münster, 48149, Germany.
[Ti] Título:An unexplored pathway for degradation of cholate requires a 7α-hydroxysteroid dehydratase and contributes to a broad metabolic repertoire for the utilization of bile salts in Novosphingobium sp. strain Chol11.
[So] Source:Environ Microbiol;18(12):5187-5203, 2016 Dec.
[Is] ISSN:1462-2920
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Bile salts such as cholate are surface-active steroid compounds with functions for digestion and signaling in vertebrates. Upon excretion into soil and water bile salts are an electron- and carbon-rich growth substrate for environmental bacteria. Degradation of bile salts proceeds via intermediates with a 3-keto-Δ -diene structure of the steroid skeleton as shown for e.g. Pseudomonas spp. Recently, we isolated bacteria degrading cholate via intermediates with a 3-keto-7-deoxy-Δ -structure of the steroid skeleton suggesting the existence of a second pathway for cholate degradation. This potential new pathway was investigated with Novosphingobium sp. strain Chol11. A 7α-hydroxysteroid dehydratase encoded by hsh2 was identified, which was required for the formation of 3-keto-7-deoxy-Δ -metabolites. A hsh2 deletion mutant could still grow with cholate but showed impaired growth. Cholate degradation of this mutant proceeded via 3-keto-Δ -diene metabolites. Heterologous expression of Hsh2 in the bile salt-degrading Pseudomonas sp. strain Chol1 led to the formation of a dead-end steroid with a 3-keto-7-deoxy-Δ -diene structure. Hsh2 is the first steroid dehydratase with an important function in a metabolic pathway of bacteria that use bile salts as growth substrates. This pathway contributes to a broad metabolic repertoire of Novosphingobium strain Chol11 that may be advantageous in competition with other bile salt-degrading bacteria.
[Mh] Termos MeSH primário: Alphaproteobacteria/metabolismo
Proteínas de Bactérias/metabolismo
Ácidos e Sais Biliares/metabolismo
Colatos/metabolismo
Hidroxiesteroide Desidrogenases/metabolismo
[Mh] Termos MeSH secundário: Alphaproteobacteria/enzimologia
Alphaproteobacteria/genética
Animais
Bactérias/metabolismo
Proteínas de Bactérias/genética
Biodegradação Ambiental
Hidroxiesteroide Desidrogenases/genética
Hidroxiesteroides/metabolismo
Redes e Vias Metabólicas
Pseudomonas/genética
Pseudomonas/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (Bile Acids and Salts); 0 (Cholates); 0 (Hydroxysteroids); EC 1.1.- (Hydroxysteroid Dehydrogenases)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170807
[Lr] Data última revisão:
170807
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160921
[St] Status:MEDLINE
[do] DOI:10.1111/1462-2920.13534


  4 / 201 MEDLINE  
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[PMID]:27185788
[Au] Autor:Eade CR; Hung CC; Bullard B; Gonzalez-Escobedo G; Gunn JS; Altier C
[Ad] Endereço:Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA cre43@cornell.edu.
[Ti] Título:Bile Acids Function Synergistically To Repress Invasion Gene Expression in Salmonella by Destabilizing the Invasion Regulator HilD.
[So] Source:Infect Immun;84(8):2198-208, 2016 Aug.
[Is] ISSN:1098-5522
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Salmonella spp. are carried by and can acutely infect agricultural animals and humans. After ingestion, salmonellae traverse the upper digestive tract and initiate tissue invasion of the distal ileum, a virulence process carried out by the type III secretion system encoded within Salmonella pathogenicity island 1 (SPI-1). Salmonellae coordinate SPI-1 expression with anatomical location via environmental cues, one of which is bile, a complex digestive fluid that causes potent repression of SPI-1 genes. The individual components of bile responsible for SPI-1 repression have not been previously characterized, nor have the bacterial signaling processes that modulate their effects been determined. Here, we characterize the mechanism by which bile represses SPI-1 expression. Individual bile acids exhibit repressive activity on SPI-1-regulated genes that requires neither passive diffusion nor OmpF-mediated entry. By using genetic methods, the effects of bile and bile acids were shown to require the invasion gene transcriptional activator hilD and to function independently of known upstream signaling pathways. Protein analysis techniques showed that SPI-1 repression by bile acids is mediated by posttranslational destabilization of HilD. Finally, we found that bile acids function synergistically to achieve the overall repressive activity of bile. These studies demonstrate a common mechanism by which diverse environmental cues (e.g., certain short-chain fatty acids and bile acids) inhibit SPI-1 expression. These data provide information relevant to Salmonella pathogenesis during acute infection in the intestine and during chronic infection of the gallbladder and inform the basis for development of therapeutics to inhibit invasion as a means of repressing Salmonella pathogenicity.
[Mh] Termos MeSH primário: Ácidos e Sais Biliares/farmacologia
Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos
Salmonella/efeitos dos fármacos
Salmonella/fisiologia
Fatores de Transcrição/metabolismo
[Mh] Termos MeSH secundário: Proteínas de Bactérias/metabolismo
Colatos/farmacologia
Sinergismo Farmacológico
Porinas/genética
Porinas/metabolismo
Estabilidade Proteica/efeitos dos fármacos
Virulência/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (Bile Acids and Salts); 0 (Cholates); 0 (HilD protein, Salmonella typhimurium); 0 (OmpC protein); 0 (OmpF protein); 0 (Porins); 0 (Transcription Factors)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170516
[Lr] Data última revisão:
170516
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160518
[St] Status:MEDLINE
[do] DOI:10.1128/IAI.00177-16


  5 / 201 MEDLINE  
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[PMID]:26691005
[Au] Autor:Holert J; Yücel O; Jagmann N; Prestel A; Möller HM; Philipp B
[Ad] Endereço:Institut für Molekulare Mikrobiologie und Biotechnologie, Westfälische Wilhelms-Universität Münster, Corrensstr. 3, Münster, 48149, Germany.
[Ti] Título:Identification of bypass reactions leading to the formation of one central steroid degradation intermediate in metabolism of different bile salts in Pseudomonas sp. strain Chol1.
[So] Source:Environ Microbiol;18(10):3373-3389, 2016 Oct.
[Is] ISSN:1462-2920
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The bile salts cholate, deoxycholate, chenodeoxycholate and lithocholate are released from vertebrates into soil and water where environmental bacteria degrade these widespread steroid compounds. It was investigated whether different enzymes are required for the degradation of these tri-, di- and monohydroxylated bile salts in the model organism Pseudomonas sp. strain Chol1. Experiments with available and novel mutants showed that the degradation of the C -carboxylic side chain attached to the steroid skeleton is catalysed by the same set of enzymes. A difference was found for the degradation of partially degraded bile salts consisting of H-methylhexahydroindanone-propanoates (HIPs). With deoxycholate and lithocholate, which lack a hydroxy group at C7 of the steroid skeleton, an additional acyl-coenzyme A (CoA) dehydrogenase was required for ß-oxidation of the C -carboxylic side chain attached to the methylhexahydroindanone moiety. The ß-oxidation of this side chain could be measured in vitro. With cholate and deoxycholate, a reductive dehydroxylation of the C12-hydroxy group of HIP was required. Deletion of candidate genes for this reaction step revealed that a so-far unknown steroid dehydratase and a steroid oxidoreductase were responsible for this CoA-dependent reaction. These results showed that all bile salts are channelled into a common pathway via bypass reactions with 3'-hydroxy-HIP-CoA as central intermediate.
[Mh] Termos MeSH primário: Ácidos e Sais Biliares/metabolismo
Pseudomonas/metabolismo
Esteroides/metabolismo
[Mh] Termos MeSH secundário: Animais
Proteínas de Bactérias/genética
Proteínas de Bactérias/metabolismo
Ácidos e Sais Biliares/química
Catálise
Colatos/metabolismo
Hidroliases/genética
Hidroliases/metabolismo
Pseudomonas/genética
Esteroides/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (Bile Acids and Salts); 0 (Cholates); 0 (Steroids); EC 4.2.1.- (Hydro-Lyases)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170829
[Lr] Data última revisão:
170829
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151223
[St] Status:MEDLINE
[do] DOI:10.1111/1462-2920.13192


  6 / 201 MEDLINE  
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[PMID]:27025049
[Au] Autor:Gorenko ZA; Grinchenko OA; Veselsky SP; Baban VM
[Ti] Título:[COMPOSITION OF GASTRIC JUICE AND BILE IN RATS AT THE EXPERIMENTAL CHRONIC PANCREATITIS].
[So] Source:Fiziol Zh;61(6):86-95, 2015.
[Is] ISSN:2522-9028
[Cp] País de publicação:Ukraine
[La] Idioma:ukr
[Ab] Resumo:Chronic pancreatitis is an inflammatory disease of the pancreas, which is characterized by destruction of pancreatic secretory parenchyma and progressing exocrine and endocrine insufficiency. Usually these patients have complications as cardiovascular, renal, respiratory and liver failure, and various gastric dysfunctions. The data of clinical observations do not reveal fully the functional state of the stomach and liver in chronic pancreatitis also remains an open question about the quality of the gastric juices and bile by this pathology. Therefore our aim was to investigate the secretory functions of the stomach and liver features in rats at the experimental chronic pancreatitis. This pathology modeled using L-arginine. Basal gastric secretion was investigated in chronic experiment by aspiration method for 10th and 63rd days, and pancreas and liver--in acute experiments at 13th and 68th days after the last administration of L-arginine. It was established that the character of the secretory response of the digestive tract depends on the duration of the pathology course. On the 10th day the functional state of the gastric secretory glands in rats with chronic pancreatitis characterized by twice increase of gastric acid production but decrease the level of hexosamines on 23.8% (P < 0.001) that indicate a increase of gastric content aggressiveness and mucus producing cells secretory insufficiency. In these animals the rate of total protein decreased on 61.7% (P < 0.05). On the 13th day observed the increase of pancreatic juice on 332% (P < 0.01), hepatic secret volume on 74.9% (P < 0.001) and redistribution in the cholates spectrum: glycocholates level increased but tauro-, free and total dehydroxylated bile acids decreased. These changes suggest deterioration of bile detergent properties, inhibition of acidic pathway of bile acids biosynthesis and conjugation of cholates with taurine. In two months total deficit of amino acids in gastric juice correlated with exocrine pancreatic insufficiency. Herein the acidity of gastric content partially restored, while the level of protein and mucus secretion proceed to decline. Consequently gastric mucosa is more vulnerable. In these rats the rates of free bile acids greatly increased while tauro- and glycocholates significantly decreased. Thus the processes of hydroxylation and conjugation of bile acids with amino acids inhibited suggesting interruption of synthetic and detoxification functions of the liver. The present work is important for comprehension the pathophysiological aspects of chronic pancreatitis particularly the digestive system functioning features at this pathology. These data could be considered in the appointment of treatment to avoid complications.
[Mh] Termos MeSH primário: Bile/química
Suco Gástrico/química
Mucosa Gástrica/metabolismo
Pancreatite Crônica/metabolismo
Estômago/metabolismo
[Mh] Termos MeSH secundário: Animais
Animais não Endogâmicos
Arginina
Ácidos e Sais Biliares/biossíntese
Ácidos e Sais Biliares/química
Colatos/metabolismo
Mucosa Gástrica/patologia
Hexosaminas/biossíntese
Hidroxilação
Fígado/metabolismo
Fígado/patologia
Masculino
Pâncreas/metabolismo
Pâncreas/patologia
Pancreatite Crônica/induzido quimicamente
Pancreatite Crônica/patologia
Biossíntese de Proteínas
Proteínas/metabolismo
Ratos
Estômago/patologia
Taurina/metabolismo
[Pt] Tipo de publicação:ENGLISH ABSTRACT; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bile Acids and Salts); 0 (Cholates); 0 (Hexosamines); 0 (Proteins); 1EQV5MLY3D (Taurine); 94ZLA3W45F (Arginine)
[Em] Mês de entrada:1604
[Cu] Atualização por classe:160330
[Lr] Data última revisão:
160330
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160331
[St] Status:MEDLINE


  7 / 201 MEDLINE  
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[PMID]:25933969
[Au] Autor:Serna M; Wong-Baeza C; Santiago-Hernández JC; Baeza I; Wong C
[Ad] Endereço:Biochemistry Department, National School of Biological Sciences, National Polytechnic Institute, Mexico City, Mexico. Electronic address: qbpsern@hotmail.com.
[Ti] Título:Hypocholesterolemic and choleretic effects of three dimethoxycinnamic acids in relation to 2,4,5-trimethoxycinnamic acid in rats fed with a high-cholesterol/cholate diet.
[So] Source:Pharmacol Rep;67(3):553-9, 2015 Jun.
[Is] ISSN:1734-1140
[Cp] País de publicação:Poland
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: 2,4,5-Trimethoxycinnamic acid (2,4,5-TMC) is the major and non-toxic metabolite of α-asarone, which retains hypocholesterolemic and choleretic activities. We compared the activities of 2,4,5-TMC with those of 2,4-dimethoxycinnamic acid (2,4-DMC), 3,4-DMC and 3,5-DMC, to understand the role of the methoxyls on carbons 2, 4 and 5 on the pharmacologic properties of these compounds. METHODS: The methoxycinnamic acids were administered to high-cholesterol/cholate-fed rats. We measured bile flow, and quantified bile acids, phospholipids and cholesterol in bile, and cholesterol and cholesterol-lipoproteins in serum. The inhibition of HMG-CoA reductase by the methoxycinnamic acids was evaluated in vitro. RESULTS: The four methoxycinnamic acids decreased serum cholesterol, without affecting the concentration of HDL-cholesterol. 2,4,5-TMC produced the highest decrease in LDL-cholesterol, 73.5%, which exceeds the range of statins (20-40%), and produced the highest inhibition of the activity of HMG-CoA reductase. 3,4-DMC produced the highest increase in bile flow, bile acids and phospholipids concentrations, and reduction in bile cholesterol, which led to a decrease in the biliary cholesterol saturation index. CONCLUSIONS: 2,4,5-TMC (which has three methoxyls) had the highest hypocholesterolemic activity, while 3,4-DMC, which lacks the methoxyl in carbon 2 but conserves the two other methoxyls in an adjacent position, had the highest choleretic activity and a probable cholelitholytic activity. In methoxycinnamic acids with two methoxyls in non-adjacent positions (2,4-DMC and 3,5-DMC), the hypocholesterolemic and choleretic activities were not as evident. 2,4,5-TMC and 3,4-DMC, which did not cause liver damage during the treatment period, should be further explored as a hypocholesterolemic and choleretic compounds in humans.
[Mh] Termos MeSH primário: Anticolesterolemiantes/uso terapêutico
Colagogos e Coleréticos/uso terapêutico
Colatos/efeitos adversos
Colesterol na Dieta/efeitos adversos
Cinamatos/uso terapêutico
Hipercolesterolemia/tratamento farmacológico
[Mh] Termos MeSH secundário: Animais
Colatos/administração & dosagem
Colesterol na Dieta/administração & dosagem
HDL-Colesterol/sangue
LDL-Colesterol/sangue
Cinamatos/química
Hipercolesterolemia/sangue
Hipercolesterolemia/induzido quimicamente
Masculino
Ratos
Ratos Wistar
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (2,4,5-trimethoxycinnamic acid); 0 (Anticholesteremic Agents); 0 (Cholagogues and Choleretics); 0 (Cholates); 0 (Cholesterol, Dietary); 0 (Cholesterol, HDL); 0 (Cholesterol, LDL); 0 (Cinnamates); U14A832J8D (cinnamic acid)
[Em] Mês de entrada:1602
[Cu] Atualização por classe:150502
[Lr] Data última revisão:
150502
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150503
[St] Status:MEDLINE


  8 / 201 MEDLINE  
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[PMID]:25824834
[Au] Autor:Sannasiddappa TH; Hood GA; Hanson KJ; Costabile A; Gibson GR; Clarke SR
[Ad] Endereço:School of Biological Sciences, University of Reading, Whiteknights, Reading, United Kingdom.
[Ti] Título:Staphylococcus aureus MnhF mediates cholate efflux and facilitates survival under human colonic conditions.
[So] Source:Infect Immun;83(6):2350-7, 2015 Jun.
[Is] ISSN:1098-5522
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Resistance to the innate defenses of the intestine is crucial for the survival and carriage of Staphylococcus aureus, a common colonizer of the human gut. Bile salts produced by the liver and secreted into the intestines are one such group of molecules with potent antimicrobial activity. The mechanisms by which S. aureus is able to resist such defenses in order to colonize and survive in the human gut are unknown. Here we show that mnhF confers resistance to bile salts, which can be abrogated by efflux pump inhibitors. MnhF mediates the efflux of radiolabeled cholic acid both in S. aureus and when heterologously expressed in Escherichia coli, rendering them resistant. Deletion of mnhF attenuated the survival of S. aureus in an anaerobic three-stage continuous-culture model of the human colon (gut model), which represents different anatomical areas of the large intestine.
[Mh] Termos MeSH primário: Proteínas de Bactérias/metabolismo
Colatos/metabolismo
Colo/fisiologia
Regulação Bacteriana da Expressão Gênica/fisiologia
Staphylococcus aureus/metabolismo
[Mh] Termos MeSH secundário: Proteínas de Bactérias/genética
Clonagem Molecular
Colo/microbiologia
Seres Humanos
Modelos Biológicos
Staphylococcus aureus/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (Cholates)
[Em] Mês de entrada:1507
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150401
[St] Status:MEDLINE
[do] DOI:10.1128/IAI.00238-15


  9 / 201 MEDLINE  
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[PMID]:25813888
[Au] Autor:Yang C; Liu SQ; Venkataraman S; Gao SJ; Ke X; Chia XT; Hedrick JL; Yang YY
[Ad] Endereço:Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, #04-01, Singapore 138669, Singapore.
[Ti] Título:Structure-directing star-shaped block copolymers: supramolecular vesicles for the delivery of anticancer drugs.
[So] Source:J Control Release;208:93-105, 2015 Jun 28.
[Is] ISSN:1873-4995
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Amphiphilic polycarbonate/PEG copolymer with a star-like architecture was designed to facilitate a unique supramolecular transformation of micelles to vesicles in aqueous solution for the efficient delivery of anticancer drugs. The star-shaped amphipilic block copolymer was synthesized by initiating the ring-opening polymerization of trimethylene carbonate (TMC) from methyl cholate through a combination of metal-free organo-catalytic living ring-opening polymerization and post-polymerization chain-end derivatization strategies. Subsequently, the self-assembly of the star-like polymer in aqueous solution into nanosized vesicles for anti-cancer drug delivery was studied. DOX was physically encapsulated into vesicles by dialysis and drug loading level was significant (22.5% in weight) for DOX. Importantly, DOX-loaded nanoparticles self-assembled from the star-like copolymer exhibited greater kinetic stability and higher DOX loading capacity than micelles prepared from cholesterol-initiated diblock analogue. The advantageous disparity is believed to be due to the transformation of micelles (diblock copolymer) to vesicles (star-like block copolymer) that possess greater core space for drug loading as well as the ability of such supramolecular structures to encapsulate DOX. DOX-loaded vesicles effectively inhibited the proliferation of 4T1, MDA-MB-231 and BT-474 cells, with IC50 values of 10, 1.5 and 1.0mg/L, respectively. DOX-loaded vesicles injected into 4T1 tumor-bearing mice exhibited enhanced accumulation in tumor tissue due to the enhanced permeation and retention (EPR) effect. Importantly, DOX-loaded vesicles demonstrated greater tumor growth inhibition than free DOX without causing significant body weight loss or cardiotoxicity. The unique ability of the star-like copolymer emanating from the methyl cholate core provided the requisite modification in the block copolymer interfacial curvature to generate vesicles of high loading capacity for DOX with significant kinetic stability that have potential for use as an anti-cancer drug delivery carrier for cancer therapy.
[Mh] Termos MeSH primário: Antineoplásicos/administração & dosagem
Antineoplásicos/química
Polímeros/química
[Mh] Termos MeSH secundário: Animais
Antibióticos Antineoplásicos/administração & dosagem
Antibióticos Antineoplásicos/farmacocinética
Antibióticos Antineoplásicos/uso terapêutico
Antineoplásicos/uso terapêutico
Linhagem Celular
Proliferação Celular/efeitos dos fármacos
Colatos/química
Preparações de Ação Retardada
Dioxanos
Doxorrubicina/administração & dosagem
Doxorrubicina/farmacocinética
Doxorrubicina/uso terapêutico
Sistemas de Liberação de Medicamentos
Feminino
Seres Humanos
Camundongos
Camundongos Endogâmicos BALB C
Conformação Molecular
Nanopartículas
Cimento de Policarboxilato
Polietilenoglicóis
Polimerização
Distribuição Tecidual
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antibiotics, Antineoplastic); 0 (Antineoplastic Agents); 0 (Cholates); 0 (Delayed-Action Preparations); 0 (Dioxanes); 0 (Polycarboxylate Cement); 0 (Polymers); 25766-59-0 (polycarbonate); 30IQX730WE (Polyethylene Glycols); 4316AQ174Q (trimethylene carbonate); 80168379AG (Doxorubicin); E1P59HQX4Q (methyl cholate)
[Em] Mês de entrada:1602
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150328
[St] Status:MEDLINE


  10 / 201 MEDLINE  
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[PMID]:25782344
[Au] Autor:Gunasekara RW; Zhao Y
[Ad] Endereço:Department of Chemistry, Iowa State University, Ames, Iowa 50011-3111, United States.
[Ti] Título:Conformationally switchable water-soluble fluorescent bischolate foldamers as membrane-curvature sensors.
[So] Source:Langmuir;31(13):3919-25, 2015 Apr 07.
[Is] ISSN:1520-5827
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Membrane curvature is an important parameter in biological processes such as cellular movement, division, and vesicle fusion and budding. Traditionally, only proteins and protein-derived peptides have been used as sensors for membrane curvature. Three water-soluble bischolate foldamers were synthesized, all labeled with an environmentally sensitive fluorophore to report their binding with lipid membranes. The orientation and ionic nature of the fluorescent label were found to be particularly important in their performance as membrane-curvature sensors. The bischolate with an NBD group in the hydrophilic α-face of the cholate outperformed the other two analogues as a membrane-curvature sensor and responded additionally to the lipid composition including the amounts of cholesterol and anionic lipids in the membranes.
[Mh] Termos MeSH primário: Colatos/química
Lipídeos de Membrana/química
Água/química
[Mh] Termos MeSH secundário: Solubilidade
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
0 (Cholates); 0 (Membrane Lipids); 059QF0KO0R (Water)
[Em] Mês de entrada:1601
[Cu] Atualização por classe:150407
[Lr] Data última revisão:
150407
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150319
[St] Status:MEDLINE
[do] DOI:10.1021/acs.langmuir.5b00379



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