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1.
J Virol ; 88(6): 3255-72, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24390322

RESUMO

UNLABELLED: BST2/tetherin inhibits the release of enveloped viruses from cells. Primate lentiviruses have evolved specific antagonists (Vpu, Nef, and Env). Here we characterized tetherin proteins of species representing both branches of the order Carnivora. Comparison of tiger and cat (Feliformia) to dog and ferret (Caniformia) genes demonstrated that the tiger and cat share a start codon mutation that truncated most of the tetherin cytoplasmic tail early in the Feliformia lineage (19 of 27 amino acids, including the dual tyrosine motif). Alpha interferon (IFN-α) induced tetherin and blocked feline immunodeficiency virus (FIV) replication in lymphoid and nonlymphoid feline cells. Budding of bald FIV and HIV particles was blocked by carnivore tetherins. However, infectious FIV particles were resistant, and spreading FIV replication was uninhibited. Antagonism mapped to the envelope glycoprotein (Env), which rescued FIV from carnivore tetherin restriction when expressed in trans but, in contrast to known antagonists, did not rescue noncognate particles. Also unlike the primate lentiviral antagonists, but similar to the Ebola virus glycoprotein, FIV Env did not reduce intracellular or cell surface tetherin levels. Furthermore, FIV-enveloped FIV particles actually required tetherin for optimal release from cells. The results show that FIV Envs mediate a distinctive tetherin evasion. Well adapted to a phylogenetically ancient tetherin tail truncation in the Felidae, it requires functional virion incorporation of Env, and it shields the budding particle without downregulating plasma membrane tetherin. Moreover, FIV has evolved dependence on this protein: particles containing FIV Env need tetherin for optimal release from the cell, while Env(-) particles do not. IMPORTANCE: HIV-1 antagonizes the restriction factor tetherin with the accessory protein Vpu, while HIV-2 and the filovirus Ebola use their envelope (Env) glycoproteins for this purpose. It turns out that the FIV tetherin antagonist is also its Env protein, but the mechanism is distinctive. Unlike other tetherin antagonists, FIV Env cannot act in trans to rescue vpu-deficient HIV-1. It must be incorporated specifically into FIV virions to be active. Also unlike other retroviral antagonists, but similar to Ebola virus Env, it does not act by downregulating or degrading tetherin. FIV Env might exclude tetherin locally or direct assembly to tetherin-negative membrane domains. Other distinctive features are apparent, including evidence that this virus evolved an equilibrium in which tetherin is both restriction factor and cofactor, as FIV requires tetherin for optimal particle release.


Assuntos
Antígenos CD/metabolismo , Doenças do Gato/metabolismo , Vírus da Imunodeficiência Felina/metabolismo , Infecções por Lentivirus/veterinária , Proteínas do Envelope Viral/metabolismo , Vírion/metabolismo , Sequência de Aminoácidos , Animais , Antígenos CD/química , Antígenos CD/genética , Doenças do Gato/genética , Doenças do Gato/virologia , Gatos , Cães , Vírus da Imunodeficiência Felina/química , Vírus da Imunodeficiência Felina/genética , Infecções por Lentivirus/genética , Infecções por Lentivirus/metabolismo , Infecções por Lentivirus/virologia , Dados de Sequência Molecular , Alinhamento de Sequência , Proteínas do Envelope Viral/genética , Vírion/genética
2.
J Nat Med ; 67(3): 619-25, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23179316

RESUMO

The fruits of saw palmetto have been used for the treatment of a variety of urinary and reproductive system problems. In this study we investigated whether the fruit extracts affect in vitro adipogenesis. Saw palmetto ethanol extract inhibited the lipid droplet accumulation by induction media in a dose-dependent manner, and it also attenuated the protein expressions of C-EBPα and PPARγ. Phosphorylation of Erk1/2 and Akt1 were also decreased by saw palmetto ethanol extract. This report suggests that saw palmetto extracts selectively affect the adipocyte differentiation through the modulation of several key factors that play a critical role during adipogenesis.


Assuntos
Adipócitos/efeitos dos fármacos , Adipogenia/efeitos dos fármacos , Extratos Vegetais/farmacologia , Serenoa/química , Células 3T3-L1 , Adipócitos/metabolismo , Animais , Proteínas Estimuladoras de Ligação a CCAAT/metabolismo , Relação Dose-Resposta a Droga , Etanol/química , Frutas , Camundongos , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , PPAR gama/metabolismo , Fosforilação , Fitoterapia , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Plantas Medicinais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Solventes/química
3.
Eur J Pharmacol ; 671(1-3): 18-25, 2011 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-21963454

RESUMO

Dehydroleucodine (DhL) is a sesquiterpene lactone of the guaianolide group with gastric cytoprotective activity. Recent studies have also demonstrated that DhL inhibits the proliferation of vascular smooth muscle cells. In this study we examined the effect of DhL in the differentiation of 3T3-L1 preadipocytes. The addition of DhL significantly inhibited the differentiation of 3T3-L1 preadipocytes along with a significant decrease in the accumulation of lipid content by a dramatic downregulation of the expression of adipogenic-specific transcriptional factors PPARγ and C-EBPα. However, phosphorylation of AMPKα, Erk1/2 and Akt1 was not inhibited by DhL treatment. Interestingly, we also found that 11,13-dihydrodehydroleucodine, a derivative of DhL with inactivated α-methylene-γ-lactone function, also inhibited the differentiation of 3T3-L1 preadipocytes. Taken together, these data suggest that DhL has an important inhibitory effect in cellular pathways regulating adipocyte differentiation by modulating the PPARγ expression, which is known to play a pivotal role during adipogenesis.


Assuntos
Adipócitos/citologia , Adipócitos/efeitos dos fármacos , Adipogenia/efeitos dos fármacos , Lactonas/farmacologia , Sesquiterpenos/farmacologia , Células 3T3-L1 , Adipócitos/metabolismo , Animais , Camundongos , Fatores de Transcrição/antagonistas & inibidores , Fatores de Transcrição/metabolismo
4.
Caracas; s.n; nov. 1996. 20 p. ilus, tab.
Tese em Espanhol | LILACS | ID: lil-213229

RESUMO

El presente estudio estuvo constituido por 100 pacientes que consultaron al Servicio de Ginecología de la Maternidad Concepción Palacios, entre septiembre de 1995 y septiembre de 1996 presentando patología con indicación de biopsia endocervical. Se asignaron al azar en 2 grupos, un grupo de estudio donde se practicó la biopsia con cánula de Pipelle y un grupo de control donde se usó la cureta de Duncan. Los grupos fueron similares en edad y paridad. El 44 por ciento de las pacientes del grupo de estudio no reportó dolor, mientras que el 100 por ciento del grupo control reportó algún grado de dolor. Comparando ambos métodos, con respecto a cantidad de sangre y tejido endocervical, no existieron diferencias estadísticamente significativas. Se concluyó que el uso de la cánula de Pipelle es mejor tolerada por las pacientes, manteniendo la cantidad y calidad de la muestra para diagnóstico histológico


Assuntos
Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Útero/citologia , Útero/patologia , Biópsia/instrumentação , Dilatação e Curetagem , Ginecologia , Obstetrícia
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