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1.
Biochemistry (Mosc) ; 84(9): 1093-1106, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31693469

RESUMO

Differential expression of 30,003 genes was studied in the liver of female Wistar rats fed with isocaloric diets with the excess of fat, fructose, or cholesterol, or their combinations for 62 days using the method of whole-transcriptome profiling on a microchip. Relative mRNA expression levels of the Asah2, Crot, Crtc2, Fmo3, GSTA2, LOC1009122026, LOC102551184, NpY, NqO1, Prom1, Retsat, RGD1305464, Tmem104, and Whsc1 genes were also determined by RT-qPCR. All the tested diets affected differently the key metabolic pathways (KEGGs). Significant changes in the expression of steroid metabolism gene were observed in the liver of animals fed with the tested diets (except the high-fat high fructose diet). Both high-fat and high-fructose diets caused a significant decrease in the expression of squalene synthase (FDFT1 gene) responsible for the initial stage of cholesterol synthesis. On the contrary, in animals fed with the high-cholesterol diet (0.5% cholesterol), expression of the FDFT1 gene did not differ from the control group; however, these animals were characterized by changes in the expression of glucose and glycogen synthesis genes, which could lead to the suppression of glycogen synthesis and gluconeogenesis. At the same time, this group demonstrated different liver tissue morphology in comparison with the animals fed with the high-fructose high-fat diet, manifested as the presence of lipid vacuoles of a smaller size in hepatocytes. The high-fructose and high-fructose high-fat diets affected the metabolic pathways associated with intracellular protein catabolism (endocytosis, phagocytosis, proteasomal degradation, protein processing in the endoplasmic reticulum), tight junctions and intercellular contacts, adhesion molecules, and intracellular RNA transport. Rats fed with the high-fructose high-fat or high-cholesterol diets demonstrated consistent changes in the expression of the Crot, Prom1, and RGD1305464 genes, which reflected a coordinated shift in the regulation of lipid and carbohydrate metabolisms.


Assuntos
Colesterol/farmacologia , Gorduras na Dieta/farmacologia , Açúcares da Dieta/farmacologia , Frutose/farmacologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , RNA/genética , Transcriptoma/efeitos dos fármacos , Animais , Colesterol/administração & dosagem , Colesterol/metabolismo , Biologia Computacional , Gorduras na Dieta/administração & dosagem , Gorduras na Dieta/metabolismo , Açúcares da Dieta/administração & dosagem , Açúcares da Dieta/metabolismo , Feminino , Frutose/administração & dosagem , Frutose/metabolismo , Perfilação da Expressão Gênica , Fígado/citologia , RNA/análise , RNA/isolamento & purificação , Ratos , Ratos Wistar , Transcriptoma/genética
2.
Cell Biochem Biophys ; 77(4): 309-317, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31625023

RESUMO

The cholesterol (Chol) content in the fiber cell plasma membranes of the eye lens is extremely high, exceeding the solubility threshold in the lenses of old humans. This high Chol content forms pure Chol bilayer domains (CBDs) and Chol crystals in model membranes and membranes formed from the total lipid extracts from human lenses. CBDs have been detected using electron paramagnetic resonance (EPR) spin-labeling approaches. Here, we confirm the presence of CBDs in giant unilamellar vesicles prepared using the electroformation method from Chol/1-palmitoyl-2-oleoylphosphocholine and Chol/distearoylphosphatidylcholine mixtures. Confocal microscopy experiments using phospholipid (PL) analog (1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine-5,5'-disulfonic acid) and cholesterol analog fluorescent probes (23-(dipyrrometheneboron difluoride)-24-norcholesterol) were performed, allowing us to make three major conclusions: (1) In all membranes with a Chol/PL mixing ratio (expressed as a molar ratio) >2, pure CBDs were formed within the bulk PL bilayer saturated with Chol. (2) CBDs were present as the pure Chol bilayer and not as separate patches of Chol monolayers in each leaflet of the PL bilayer. (3) CBDs, presented as single large domains, were always located at the top of giant unilamellar vesicles, independent of the change in sample orientation (right-side-up/upside-down). Results obtained with confocal microscopy and fluorescent Chol and PL analogs, combined with those obtained using EPR and spin-labeled Chol and PL analogs, contribute to the understanding of the organization of lipids in the fiber cell plasma membranes of the human eye lens.


Assuntos
Colesterol/química , Microscopia Confocal , Fosfatidilcolinas/química , Lipossomas Unilamelares/química , Colesterol/metabolismo , Espectroscopia de Ressonância de Spin Eletrônica , Corantes Fluorescentes/química , Humanos , Cristalino/metabolismo , Bicamadas Lipídicas/química , Lipossomas Unilamelares/metabolismo
3.
Med. infant ; 26(3): 287-295, Septiembre 2019. Tab, ilus
Artigo em Espanhol | LILACS | ID: biblio-1025029

RESUMO

La Hipercolesterolemia Familiar (HF) es una enfermedad hereditaria frecuente que se caracteriza por niveles elevados de colesterol ligado a las lipoproteínas de baja densidad (C-LDL). El exceso de LDL se acumula en las arterias produciendo aterosclerosis prematura. El diagnóstico y tratamiento desde la infancia mejoran el pronóstico de la enfermedad. Existe subdiagnóstico de la HF lo que provoca muertes prematuras por enfermedad cardiovascular (ECV). Para mejorar el subdiagnóstico la Sociedad Argentina de Pediatría propuso en el año 2015 realizar tamizaje universal al ingreso escolar. Es relevante entonces que el pediatra pueda diagnosticar la hipercolesterolemia y diferenciar las hipercolesterolemias monogénicas o familiares, de las secundarias (AU)


Familial hypercholesterolemia (FH) is a common hereditary disease that is characterized by high cholesterol levels, linked to low-density lipoproteins (LDL). Excess LDL accumulates in the arteries leading to premature atherosclerosis. Early diagnosis and treatment since childhood improve the prognosis of the disease. FH is underdiagnosed resulting in premature death due to cardiovascular disease (CVD). To improve diagnosis, in 2015 the Argentine Society of Pediatrics proposed a universal screening program at school age. It is relevant, therefore, for the pediatrician to be able to diagnose hypercholesterolemia and differentiate monogenic or familial from secondary hypercholesterolemia (AU)


Assuntos
Humanos , Pré-Escolar , Criança , Adolescente , Doenças Cardiovasculares/prevenção & controle , Colesterol/metabolismo , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/fisiopatologia , Hiperlipoproteinemia Tipo II/genética , Hiperlipoproteinemia Tipo II/terapia , Programas de Rastreamento , Diagnóstico Diferencial , Anticolesterolemiantes/uso terapêutico
4.
J Agric Food Chem ; 67(40): 11119-11128, 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31525874

RESUMO

Xanthohumol (Xan) is a prenylated chalcone mainly found in hops; it has been demonstrated to function against hypercholesterolemia, hyperlipidemia, and atherosclerosis. In this study, we focused on the hypocholesterolemic effect of Xan on cholesterol uptake and the underlying molecular mechanisms of Xan in human intestinal Caco-2 cells. The microarray data showed that Niemann-Pick C1-like 1 (NPC1L1), an essential transporter for dietary cholesterol absorption, was significantly downregulated in Xan-treated Caco-2 cells. We demonstrated that Xan (10 and 20 µM) suppressed the mRNA and protein expression of NPC1L1 by 0.65 ± 0.12-fold and 0.54 ± 0.15-fold and 0.72 ± 0.04-fold and 0.44 ± 0.12-fold, respectively, compared to that of the vehicle-treated Caco-2 cells. Moreover, Xan (10 and 20 µM) significantly inhibited cholesterol uptake by approximately 12 and 32% in Caco-2 cells. NPC1L1 promoter activity was significantly suppressed by Xan, and a DNA element within the NPC1L1 promoter involved in Xan-mediated NPC1L1 reduction located between the -120 and -20 positions was identified. Moreover, Xan markedly decreased the mRNA and protein levels of hepatocyte nuclear factor 4α (HNF-4α), a critical activator of NPC1L1 transcription, and subsequently attenuated HNF-4α/NPC1L1 promoter complex formation, resulting in the suppression of NPC1L1 gene expression. Finally, we demonstrated that Xan markedly abolished lovastatin-induced NPC1L1 overexpression in Caco-2 cells. These findings reveal that Xan suppresses NPC1L1 expression via downregulation of HNF-4α and exerts inhibitory effects on cholesterol uptake in the intestinal Caco-2 cells. Our findings suggest Xan could serve as a potential cholesterol-lowering agent and supplement for statin therapy.


Assuntos
Colesterol/metabolismo , Flavonoides/farmacologia , Fator 4 Nuclear de Hepatócito/metabolismo , Proteínas de Membrana/genética , Propiofenonas/farmacologia , Anticolesterolemiantes/farmacologia , Transporte Biológico/efeitos dos fármacos , Células CACO-2 , Regulação para Baixo/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Fator 4 Nuclear de Hepatócito/genética , Humanos , Proteínas de Membrana/metabolismo , Regiões Promotoras Genéticas
5.
J Agric Food Chem ; 67(40): 11167-11178, 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31542928

RESUMO

Milk contains a number of beneficial fatty acids including short and medium chain and unsaturated conjugated and nonconjugated fatty acids. In this study, microRNA sequencing of mammary tissue collected in early-, peak-, mid-, and late-lactation periods was performed to determine the miRNA expression profiles. miR-16a was one of the differentially expressed miRNA and was selected for in-depth functional studies pertaining to fatty acid metabolism. The mimic of miR-16a impaired fat metabolism [triacylglycerol (TAG) and cholesterol] while knock-down of miR-16a promoted fat metabolism in vitro in bovine mammary epithelial cells (BMECs). In addition, the in vitro work with BMECs also revealed that miR-16a had a negative effect on the cellular concentration of cis 9-C18:1, total C18:1, C20:1, and C22:1 and long-chain polyunsaturated fatty acids. Therefore, these data suggesting a negative effect on fatty acid metabolism extend the discovery of the key role of miR-16a in mediating adipocyte differentiation. Through a combination of bioinformatics analysis, target gene 3' UTR luciferase reporter assays, and western blotting, we identified large tumor suppressor kinase 1 (LATS1) as a target of miR-16a. Transfection of siRNA-LATS1 into BMECs led to increases in TAG, cholesterol, and cellular fatty acid concentrations, suggesting a positive role of LATS1 in mammary cell fatty acid metabolism. In summary, data suggest that miR-16a regulates biological processes associated with intracellular TAG, cholesterol, and unsaturated fatty acid synthesis through LATS1. These data provide a theoretical and experimental framework for further clarifying the regulation of lipid metabolism in mammary cells of dairy cows.


Assuntos
Bovinos/metabolismo , Células Epiteliais/enzimologia , Metabolismo dos Lipídeos , Glândulas Mamárias Animais/enzimologia , MicroRNAs/metabolismo , Leite/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Animais , Bovinos/genética , Colesterol/metabolismo , Células Epiteliais/metabolismo , Ácidos Graxos/metabolismo , Feminino , Regulação da Expressão Gênica , Glândulas Mamárias Animais/metabolismo , MicroRNAs/genética , Proteínas Serina-Treonina Quinases/genética , Triglicerídeos/metabolismo
6.
J Agric Food Chem ; 67(40): 11044-11052, 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31545599

RESUMO

Persimmon condensed tannins (PT) are highly polymerized (mDP = 26) and highly galloylated (72%) proanthocyanidins. Its pleiotropic effects in oxidation resistance, neuroprotection, hypolipidemia, and cardio-protection both in vitro and in vivo were widely reported. Because large proanthocyanidins are unlikely to be absorbed in the gastrointestinal tract, it is believed that the interaction of PT with biological membranes may play a crucial role in its biological activities. In the present study, the capacities of PT adsorbing to membrane, partitioning into membrane, and its influence on the membrane fluidity were investigated by fluorescence quenching, isothermal titration calorimetry (ITC) and fluorescence anisotropy measurements in a biomembrane-mimetic system composed of 1-palmitoyl-2-oleoylphosphatidylcholine (POPC), 1-palmitoyl-2-oleoylphosphatidylethanolamine (POPE), sphingomyelin (SPM), and cholesterol (CHOL). Besides, the effects of PT on the morphology and integrity of the cell membrane were studied by scanning electron microscopy (SEM) and fluorescence staining in the 3T3-L1 cell model. The results suggested that PT could affect cell membrane rafts domains, destroy the cell membrane morphology, and regulate cell membrane fluidity, which might contribute to its biological effects.


Assuntos
Membrana Celular/química , Diospyros/química , Extratos Vegetais/química , Proantocianidinas/química , Animais , Fenômenos Biofísicos , Membrana Celular/metabolismo , Colesterol/química , Colesterol/metabolismo , Frutas/química , Fluidez de Membrana , Camundongos , Células NIH 3T3 , Fosfatidilcolinas/química , Fosfatidilcolinas/metabolismo , Extratos Vegetais/metabolismo , Polimerização , Proantocianidinas/metabolismo , Esfingomielinas/química , Esfingomielinas/metabolismo
7.
Nat Cell Biol ; 21(10): 1206-1218, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31548609

RESUMO

Cholesterol activates the master growth regulator, mTORC1 kinase, by promoting its recruitment to the surface of lysosomes by the Rag guanosine triphosphatases (GTPases). The mechanisms that regulate lysosomal cholesterol content to enable mTORC1 signalling are unknown. Here, we show that oxysterol binding protein (OSBP) and its anchors at the endoplasmic reticulum (ER), VAPA and VAPB, deliver cholesterol across ER-lysosome contacts to activate mTORC1. In cells lacking OSBP, but not other VAP-interacting cholesterol carriers, the recruitment of mTORC1 by the Rag GTPases is inhibited owing to impaired transport of cholesterol to lysosomes. By contrast, OSBP-mediated cholesterol trafficking drives constitutive mTORC1 activation in a disease model caused by the loss of the lysosomal cholesterol transporter, Niemann-Pick C1 (NPC1). Chemical and genetic inactivation of OSBP suppresses aberrant mTORC1 signalling and restores autophagic function in cellular models of Niemann-Pick type C (NPC). Thus, ER-lysosome contacts are signalling hubs that enable cholesterol sensing by mTORC1, and targeting the sterol-transfer activity of these signalling hubs could be beneficial in patients with NPC.


Assuntos
Colesterol/metabolismo , Retículo Endoplasmático/metabolismo , Lisossomos/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Doenças de Niemann-Pick/metabolismo , Receptores de Esteroides/metabolismo , Animais , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Células HEK293 , Humanos , Alvo Mecanístico do Complexo 1 de Rapamicina/genética , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Camundongos , Receptores de Esteroides/genética , Transdução de Sinais , Proteínas de Transporte Vesicular/genética , Proteínas de Transporte Vesicular/metabolismo
8.
Adv Exp Med Biol ; 1161: 243-253, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31562634

RESUMO

Flavonoids are plant secondary metabolites that act as protectants against harmful effects of UV-B radiation inasmuch as biotic stress, conferring at the same time pigmentation of fruits and leaves [67]. The term "flavonoid" refers to phenolics having a basic skeleton of diphenylpropane (C6-C3-C6), which consists of two aromatic rings linked through three carbons that usually form an oxygenated heterocycle [25, 52]. Flavonoids are broken down into several different sub-categories based on their chemical structure. The main subclasses commonly found in food items are: flavonols, flavones, flavanones, flavan-3-ols, proanthocyanidins, and anthocyanins [44, 67]. Figure 19.1 depicts the major classification of flavonoids according to their chemical structure. Their occurrence in food matrices has been extensively reviewed [39, 44], and has been subject of extensive research in the last decades. Table 19.1 contains a few examples of compounds from each of the subcategory, with the fruit (berry) in which they are commonly found. The monomeric unit of flavonoids can dimerize and polymerize to form other important high molecular weight molecules; this is the case of proanthocyanidins, that are polymers of flavan-3-ols or flavanols. Not only do these compounds act as plant protectants, but they can also be very beneficial to human health. Cohorts studies performed in the early '90 have shown that dietary consumption of flavonoids was inversely associated with morbidity and mortality from coronary heart disease [31, 32]. These findings have opened an intensive field of research on the effects of flavonoids and flavonoids-rich food extracts in cardiovascular diseases (CVD) progression, particularly in the modulating CVD-associated oxidative stress and inflammation. In this short review, we will summarize the current findings in flavonoids beneficial effects in preventing CVD through inhibition of initial stages of CVD progression. Given the magnitude of scientific literature in the field, we will focus on two strictly mechanistic aspects: inhibition of chemical-induced LDL oxidation, and the effect of flavonoids in the monocyte/macrophages activation pathways.


Assuntos
Colesterol , Flavonoides , Metabolismo dos Lipídeos , Colesterol/metabolismo , Dieta , Flavonoides/metabolismo , Humanos , Inflamação/fisiopatologia , Oxirredução
9.
Cell Physiol Biochem ; 53(3): 550-572, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31529928

RESUMO

BACKGROUND/AIMS: Atherosclerosis underlies the majority of cardiovascular events, consequent to non-resolving inflammation. Considerable evidence implicates autophagy dysfunction at the core of this inflammatory condition, but the basis of this dysfunction is not fully understood. METHODS: Using an in vitro model of lipid-laden macrophages, activity-based probes and high-throughput techniques, we studied the role of the cysteine proteases cathepsins in autophagy. RESULTS: We showed that cathepsin activity is suppressed by oxidized lipids and that cathepsin has an indispensable role in the autophagy-lysosomal degradation pathway. Accordingly, loss of cathepsin function resulted in autophagy derangement. Shotgun proteomics confirmed autophagy dysfunction and unveiled a pivotal role of cathepsin L in a putative cathepsin degradation network. At the physiological level, cathepsin inhibition resulted in mitochondrial stress, which translated into impaired oxidative metabolism, excessive production of reactive oxygen species and activation of the cellular stress response, driven by ATF4-CHOP transcription factors. In addition, transcriptomic analysis of these cells uncovered some genetic similarities with the inflammatory macrophage phenotype (a.k.a M1 macrophages) and increased expression of inflammatory cytokines. CONCLUSION: Our data highlight the importance of cathepsins for mitochondrial quality control mechanisms and amelioration of vascular inflammation.


Assuntos
Anti-Inflamatórios/farmacologia , Catepsina B/metabolismo , Catepsina L/metabolismo , Catepsinas/metabolismo , Macrófagos/metabolismo , Animais , Autofagia/efeitos dos fármacos , Células da Medula Óssea/citologia , Catepsina B/antagonistas & inibidores , Catepsina L/antagonistas & inibidores , Células Cultivadas , Colesterol/metabolismo , Humanos , Macrófagos/efeitos dos fármacos , Masculino , Espectrometria de Massas , Camundongos , Camundongos Knockout , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Dinâmica Mitocondrial , Estresse Oxidativo/efeitos dos fármacos , Proteômica/métodos , Células RAW 264.7 , Espécies Reativas de Oxigênio/metabolismo
10.
Nat Methods ; 16(9): 866-869, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31451765

RESUMO

Auxin-inducible degron technology allows rapid and controlled protein depletion. However, basal degradation without auxin and inefficient auxin-inducible depletion have limited its utility. We have identified a potent auxin-inducible degron system composed of auxin receptor F-box protein AtAFB2 and short degron miniIAA7. The system showed minimal basal degradation and enabled rapid auxin-inducible depletion of endogenous human transmembrane, cytoplasmic and nuclear proteins in 1 h with robust functional phenotypes.


Assuntos
Proteínas de Arabidopsis/metabolismo , Carcinoma de Células Escamosas/metabolismo , Ácidos Indolacéticos/farmacologia , Proteólise/efeitos dos fármacos , Receptores de Superfície Celular/metabolismo , Neoplasias Cutâneas/metabolismo , Fatores de Transcrição/metabolismo , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Colesterol/metabolismo , Citoplasma/metabolismo , Células HEK293 , Humanos , Reguladores de Crescimento de Planta/farmacologia , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Células Tumorais Cultivadas
12.
Nat Cell Biol ; 21(8): 991-1002, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31371828

RESUMO

Migrasomes are recently discovered cellular organelles that form as large vesicle-like structures on retraction fibres of migrating cells. While the process of migrasome formation has been described before, the molecular mechanism underlying migrasome biogenesis remains unclear. Here, we propose that the mechanism of migrasome formation consists of the assembly of tetraspanin- and cholesterol-enriched membrane microdomains into micron-scale macrodomains, which swell into migrasomes. The major finding underlying the mechanism is that tetraspanins and cholesterol are necessary and sufficient for migrasome formation. We demonstrate the necessity of tetraspanins and cholesterol via live-cell experiments, and their sufficiency by generating migrasome-like structures in reconstituted membrane systems. We substantiate the mechanism by a theoretical model proposing that the key factor driving migrasome formation is the elevated membrane stiffness of the tetraspanin- and cholesterol-enriched macrodomains. Finally, the theoretical model was quantitatively validated by experimental demonstration of the membrane-stiffening effect of tetraspanin 4 and cholesterol.


Assuntos
Colesterol/metabolismo , Microdomínios da Membrana/metabolismo , Tetraspaninas/metabolismo , Linhagem Celular , Movimento Celular/fisiologia , Humanos , Proteínas de Membrana/metabolismo , Organelas/metabolismo
13.
DNA Cell Biol ; 38(10): 1048-1055, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31433200

RESUMO

DNA condensed agents can improve the transfection efficiency of the cationic liposome delivery system. However, various condensed agents have distinct transfection efficiency and cellular cytotoxicity. The object of this study was to screen the optimal agents with the high transfection efficiency and low cytotoxicity from four polymer compressive materials, polyethylenimine (PEI), chitosan, poly-l-lysine (PLL), and spermidine. DNA was precompressed with these four agents and then combined to cationic liposomes. Subsequently, the entrapment and transfection efficiency of the obtained complexes were investigated. Finally, the particle sizes, cytotoxicity, and endocytosis fashion of these copolymers (Lipo-PEI, Lipo-chitosan, Lipo-PLL, and Lipo-spermidine) were examined. It was found that these four copolymers had significantly lower cytotoxicity and higher transfection efficiency (45.5%, 42.4%, 36.8%, and 47.4%, respectively) than those in the control groups. The transfection efficiency of Lipo-PEI and Lipo-spermidine copolymers were better than the other two copolymers. In 293T cells, nystatin significantly inhibited the transfection efficiency of Lipo-PEI-DNA and Lipo-spermidine-DNA (51.88% and 46.05%, respectively), which suggest that the endocytosis pathway of Lipo-spermidine and Lipo-PEI copolymers was probably caveolin dependent. Our study indicated that these dual-degradable copolymers especially liposome-spermidine copolymer could be used as the potential biocompatible gene delivery carriers.


Assuntos
Quitosana/química , Lipossomos/química , Polietilenoimina/química , Polilisina/química , Espermidina/química , Transfecção/métodos , Cátions , Caveolina 1/genética , Caveolina 1/metabolismo , Quitosana/metabolismo , Colesterol/química , Colesterol/metabolismo , Endocitose/efeitos dos fármacos , Endocitose/genética , Ácidos Graxos Monoinsaturados/química , Ácidos Graxos Monoinsaturados/metabolismo , Células HEK293 , Humanos , Lipossomos/metabolismo , Nistatina/farmacologia , Tamanho da Partícula , Plasmídeos/química , Plasmídeos/metabolismo , Polietilenoimina/metabolismo , Polilisina/metabolismo , Compostos de Amônio Quaternário/química , Compostos de Amônio Quaternário/metabolismo , Espermidina/metabolismo
14.
Food Chem ; 301: 125198, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31374533

RESUMO

The experiment was conducted to evaluate the effects of five rubber seed oil (RSO) levels (0, 1%, 2%, 4%, and 6%) on hens laying performance, egg quality, and yolks fatty acid composition and cholesterol contents. Three hundred and sixty 30-week-old Lohmann Brown laying hens were allotted to 5 groups. The results showed that the egg production was increased in 4% RSO group (P < 0.05), but egg quality parameters and the contents of dry matter, lipid, and protein in yolks were not influenced among treatments (P > 0.05). Yolk cholesterol contents were reduced in RSO supplemental groups (P < 0.05). The concentration of total n-3 PUFA in yolks increased gradually while the ratio of n-6/n-3 decreased gradually with increasing dietary RSO levels (P < 0.001). In conclusion, dietary RSO supplementation increased yolk n-3 PUFA levels, improved yolk color, and reduced yolk cholesterol contents without negative influence on laying performance parameters.


Assuntos
Ração Animal , Galinhas , Colesterol/metabolismo , Gema de Ovo/química , Gorduras Insaturadas/farmacologia , Ácidos Graxos Ômega-3/metabolismo , Animais , Galinhas/metabolismo , Colesterol/análise , Suplementos Nutricionais , Gema de Ovo/metabolismo , Ácidos Graxos Ômega-3/análise , Feminino , Qualidade dos Alimentos , Armazenamento de Alimentos , Lipídeos/análise
15.
An Bras Dermatol ; 94(3): 341-343, 2019 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-31365666

RESUMO

CHILD syndrome (Congenital Hemidysplasia, Ichthyosiform erythroderma, Limb Defects) is a rare X-linked dominant disease. The authors report a 2-month-old patient presenting with typical features of CHILD syndrome that was treated with a topical solution containing cholesterol and lovastatin, with complete clearance of her CHILD nevus. The changes in skin lipid metabolism that explain the CHILD ichthyosiform nevus and their correction through topical application of cholesterol and lovastatin are discussed.


Assuntos
Anormalidades Múltiplas/tratamento farmacológico , Anticolesterolemiantes/administração & dosagem , Colesterol/metabolismo , Doenças Genéticas Ligadas ao Cromossomo X/tratamento farmacológico , Eritrodermia Ictiosiforme Congênita/tratamento farmacológico , Deformidades Congênitas dos Membros/tratamento farmacológico , Lovastatina/administração & dosagem , Anormalidades Múltiplas/genética , Administração Tópica , Colesterol/biossíntese , Feminino , Doenças Genéticas Ligadas ao Cromossomo X/genética , Humanos , Eritrodermia Ictiosiforme Congênita/genética , Lactente , Deformidades Congênitas dos Membros/genética , Doenças Metabólicas/genética
16.
Pestic Biochem Physiol ; 159: 91-97, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31400790

RESUMO

The organophosphorus pesticide, triazophos (TAP) was banned to use in agriculture in several countries due to its high toxicity. However, TAP was still widely used and frequently detected in foods. Recently, many studies reported the endocrine-disrupting effect of pesticides, especially the hypothalamic-pituitary-thyroid and hypothalamic-pituitary-gonadal axis. In this study, adult male Wistar rats were exposed to TAP at the dose of 0.164 and 1.64 mg/kg bodyweight (~1/500th and 1/50th of LD50) for 24 weeks and serum contents of hormones were measured. TAP exposure significantly reduced serum contents of adrenocorticotropic hormone, corticosterone and epinephrine in rats (p < .05), leading to the delay in glucose homeostasis during the insulin tolerance test and decrease in serum contents of total cholesterol, triglyceride and low density lipoprotein. Molecular docking results suggested TAP may be an antagonist of glucocorticoid receptor which decreased significantly in the liver of rats, resulting in the decreased expression of 11ß-hydroxysteroid dehydrogenase 1 and PEPCK1. This study revealed that TAP is a potential endocrine disruptor, especially in the hypothalamus-pituitary-adrenal system and may disturb the metabolism by affecting glucocorticoid receptor. This study provided new evidence about the toxicity of TAP and it was necessary to strictly control the usage of TAP in food.


Assuntos
Hipotálamo/efeitos dos fármacos , Organotiofosfatos/farmacologia , Praguicidas/farmacologia , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Triazóis/farmacologia , 11-beta-Hidroxiesteroide Desidrogenases/metabolismo , Animais , Colesterol/metabolismo , Lipoproteínas LDL/metabolismo , Masculino , Simulação de Acoplamento Molecular , Ratos , Ratos Wistar , Triglicerídeos/metabolismo
17.
An Acad Bras Cienc ; 91(3): e20180646, 2019 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-31411259

RESUMO

The hepatoprotective effects of the ethanolic extracts of propolis (EEP) on alcohol-induced liver steatosis were investigated in Wistar rats. Chronic alcoholic fatty liver was induced by administration of 52% alcohol to male Wistar rats at the dose of 1% body weight for 7 weeks. Then animals were simultaneously treated with 50% ethanol solutions of EEP or normal saline at the dose of 0.1% body weight for 4 further weeks. Serological analyses and liver histopathology studies were performed to investigate the development of steatosis. Microarray analysis was conducted to investigate the alterations of hepatic gene expression profiling. Our results showed that 4-week treatment of EEP helped to restore the levels of various blood indices, liver function enzymes and the histopathology of liver tissue to normal levels. Results from the microarray analysis revealed that the hepatic expressions of genes involved in lipogenesis were significantly down-regulated by EEP treatment, while the transcriptional expressions of functional genes participating in fatty acids oxidation were markedly increased. The ability of EEP to reduce the negative effects of alcohol on liver makes propolis a potential natural product for the alternative treatment of alcoholic fatty liver.


Assuntos
Fígado Gorduroso Alcoólico/metabolismo , Hepatopatias Alcoólicas/metabolismo , Extratos Vegetais/metabolismo , Própole/metabolismo , Substâncias Protetoras/metabolismo , Alanina Transaminase/metabolismo , Animais , Apiterapia/métodos , Aspartato Aminotransferases/metabolismo , Colesterol/metabolismo , Modelos Animais de Doenças , Etanol , Ácidos Graxos/biossíntese , Fígado Gorduroso Alcoólico/tratamento farmacológico , Fígado Gorduroso Alcoólico/genética , Fígado Gorduroso Alcoólico/patologia , Hepatopatias Alcoólicas/tratamento farmacológico , Hepatopatias Alcoólicas/genética , Hepatopatias Alcoólicas/patologia , Masculino , Oxirredução , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Própole/química , Própole/uso terapêutico , Substâncias Protetoras/química , Substâncias Protetoras/uso terapêutico , Ratos Wistar , Análise Serial de Tecidos/métodos , Transcrição Genética/genética , Triglicerídeos/metabolismo
18.
World J Microbiol Biotechnol ; 35(9): 131, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31432251

RESUMO

Cholesterol is a C27-sterol employed as starting material for the synthesis of valuable pharmaceutical steroids and precursors. The microbial transformations of cholesterol have been widely studied, since they are performed with high regio- and stereoselectivity and allow the production of steroidal compounds which are difficult to synthesize by classical chemical methods. In recent years, ongoing research is being conducted to discover novel biocatalysts and to develop biotechnological processes to improve existing biocatalysts and biotransformation reactions. The main objective of this review is to present the most remarkable advances in fungal and bacterial transformation of cholesterol, focusing on the different types of microbial reactions and biocatalysts, biotransformation products, and practical aspects related to sterol dispersion improvement, covering literature since 2000. It reviews the conversion of cholesterol by whole-cell biocatalysts and by purified enzymes that lead to various structural modifications, including side chain cleavage, hydroxylation, dehydrogenation/reduction, isomerization and esterification. Finally, approaches used to improve the poor solubility of cholesterol in aqueous media, such as the use of different sterol-solubilizing agents or two-phase conversion system, are also discussed.


Assuntos
Bactérias/metabolismo , Biotecnologia/métodos , Colesterol/metabolismo , Fungos/metabolismo , Bactérias/genética , Bactérias/crescimento & desenvolvimento , Biotecnologia/tendências , Biotransformação , Enzimas/metabolismo , Fungos/genética , Fungos/crescimento & desenvolvimento
19.
Curr Protein Pept Sci ; 20(10): 1004-1011, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31453783

RESUMO

Cardiovascular disease (CVD) is the biggest killer globally and atherosclerosis (AS) is the major trigger to this pathology. Abnormal cholesterol homeostasis is the starting point of AS, especially the aggregation of macrophage foam cells in the intra-arterial subcutaneous region. Reverse cholesterol transport (RCT) can remove excess cholesterol from macrophages and transport it to the liver for excretion, making this process vital to alleviate AS. MicroRNAs (miRNAs) are small, noncoding RNAs that play critical roles in various diseases including AS, by regulating post-transcriptional gene expression. Many natural compounds can exert anti-atherosclerotic effects by regulating different miRNAs that are implicated in RCT. Hence, targeting these miRNAs using natural functional compounds may be a safe, novel, and promising strategy to prevent and treat AS. This review describes the miRNAs involved in RCT and the potential uses of natural compounds to target RCT-related miRNAs to modulate AS.


Assuntos
Aterosclerose/tratamento farmacológico , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Colesterol/metabolismo , Transportadores de Cassetes de Ligação de ATP/metabolismo , Animais , Transporte Biológico/efeitos dos fármacos , Transporte Biológico/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , MicroRNAs/metabolismo
20.
Artigo em Inglês | MEDLINE | ID: mdl-31465877

RESUMO

Hypoxia-tolerant animals use metabolic suppression as an essential strategy to survive low oxygen. Ectotherms can alter membrane lipid composition in response to changes in environmental temperature, but it is currently unknown whether chronic hypoxia can also elicit membrane restructuring. The goal of this study was to investigate a possible physiological link between membrane remodelling and metabolic suppression in goldfish exposed to prolonged hypoxia (4 weeks at 10% air saturation). We have tested the hypothesis that chronic hypoxia would modulate membrane lipid composition in ways that are consistent with known mechanisms of ion pump inhibition. Because homeoviscous membrane restructuring could interfere with the response to hypoxia, measurements were made at 2 temperatures. Results show that hypoxic goldfish suppress metabolic rate by 74% (at 13 °C) and 63% (at 20 °C). This study is the first to reveal that cold-acclimated animals undergo extensive, tissue-specific restructuring of membrane lipids as they reach minimal metabolic rates. However, hypoxia does not affect membrane composition in fish acclimated to 20 °C. The strong membrane response of cold-acclimated fish involves increases in cholesterol abundance (in white muscle and gills) and in fatty acid saturation, mainly caused by a reduction in %22:6 (docosahexaenoic acid in gills and liver). Major ion pumps like Na+/K+-ATPase are known to be inhibited by cholesterol and activated by 22:6. Because ion pumping by membrane-bound ATPases accounts for a large fraction of basal cellular energy use, we propose that the membrane responses reported here could be a novel mechanism to promote metabolic suppression in cold-acclimated animals.


Assuntos
Ácidos Graxos/metabolismo , Hipóxia/metabolismo , Animais , Colesterol/metabolismo , Carpa Dourada , Temperatura Ambiente
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