Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 7 de 7
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Toxicol Mech Methods ; : 1-16, 2021 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-33467949

RESUMO

Smokeless tobacco products provide an alternative to cigarettes; however, smokeless tobacco is carcinogenic and harmful to human health. This study evaluated the toxicological effects of snus extracts and cigarette smoke total particulate matter (TPM) on human umbilical vein endothelial cells (HUVECs). Treated cells were examined for cell viability, reactive oxygen species (ROS), apoptosis, and inflammatory cytokines. Moreover, we explored the mechanism of programmed cell death induced by snus. The results showed that snus extracts significantly inhibited cell viability in a dose-dependent manner. ROS was significantly increased in treatment groups, and anti-oxidant treatment could not prevent snus extract-induced cell death. Snus extracts induced apoptosis, DNA damage, activation and cleavage of caspase-3 and caspase-8, pathway-related gene change, and interleukin (IL)-6 and IL-8 release in HUVECs. Snus extracts exposure may induce cytotoxicity, ROS generation, inflammatory cytokines release, and apoptosis or DNA damage through intrinsic and extrinsic pathways in HUVECs.

2.
Toxicol Lett ; 316: 10-19, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31476341

RESUMO

Rapid risk assessment models for different types of cigarette smoke extract (CSE) exposure are critical to understanding the etiology of chronic obstructive pulmonary disease. The present study investigated inflammation of cultured tracheal tissues with CSE exposure. Rat trachea rings were isolated, cultured, then exposed to various concentrations of CSE from 3R4 F reference cigarettes for 4 h. Tissue/cellular morphology, ultrastructure, viability and damage, inflammatory cell infiltration, and inflammatory protein levels were measured and compared to untreated controls. Human bronchial epithelial cells (BEAS-2B) exposed to 0 or 300 µg/mL CSE were cocultured with macrophages to assess extent of mobilization and phagocytosis. Endotracheal epithelium cilia densities were significantly reduced with increasing CSE concentrations, while mucous membranes became increasingly disordered; both eventually disappeared. Macrophages became larger as the CSE concentration increased, with microvilli and extended pseudopodium covering their surface, and many primary and secondary lysosomes present in the cytoplasm. Inflammatory cell infiltration also increased with increasing CSE dose, as did intracellular adhesion molecule-1(ICAM-1), interleukin-6(IL-6). The method described here may be useful to qualitatively characterized the effects of the compound under study. Then, we use BEAS-2B cell line system to strength the observation made in the cultured tissues. Probably, an approach to integrate results from both experiments will facilitate its application. These results demonstrate that cultured rat tracheal rings have a whole-tissue structure that undergoes inflammatory processes similar to in vivo tissues upon CSE exposure.


Assuntos
Células Epiteliais/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Doença Pulmonar Obstrutiva Crônica/etiologia , Fumaça/efeitos adversos , Fumar/efeitos adversos , Tabaco/efeitos adversos , Traqueia/efeitos dos fármacos , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Técnicas de Cocultura , Células Epiteliais/metabolismo , Células Epiteliais/ultraestrutura , Humanos , Mediadores da Inflamação/metabolismo , Molécula 1 de Adesão Intercelular/metabolismo , Interleucina-6/metabolismo , Macrófagos/metabolismo , Macrófagos/ultraestrutura , Masculino , Doença Pulmonar Obstrutiva Crônica/metabolismo , Doença Pulmonar Obstrutiva Crônica/patologia , Ratos Sprague-Dawley , Medição de Risco , Fatores de Tempo , Técnicas de Cultura de Tecidos , Traqueia/metabolismo , Traqueia/ultraestrutura
3.
Toxicol Mech Methods ; 29(7): 499-510, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31050318

RESUMO

The tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is classified as a Group 1 human carcinogen. It is metabolically activated by P450 enzymes to intermediate methylate and pyridyloxobutylate DNA, resulting in the formation of DNA adduct that is critical for the carcinogenicity of NNK. To directly and objectively examine the DNA adduct formation profiles without the complexity of factors in vivo, in the present study, five kinds of methyl DNA adducts were first identified in the incubation model of NNK established with human lung epithelial cells (BEAS-2B). The level of methyl DNA adducts and metabolites of NNK were quantitatively analyzed, respectively. With the increase of exposure time and dose, the level of methyl DNA adducts and metabolites increased. Furthermore, with the changes of the activity of P450 enzymes, which is the main enzyme regulating the α-hydroxylation of NNK, we found the levels of both methyl adducts and metabolites formed via α-hydroxylation in experimental groups showed the same trend compared with those in control group, while the metabolites formed via other pathways changed in the opposite trend. The result proves that the methyl adducts induced by NNK generate via α-hydroxylation pathway in BEAS-2B cells.


Assuntos
Carcinógenos/toxicidade , Adutos de DNA/metabolismo , Metilação de DNA/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Nitrosaminas/toxicidade , Carcinógenos/metabolismo , Técnicas de Cultura de Células , Linhagem Celular , Sistema Enzimático do Citocromo P-450 , Relação Dose-Resposta a Droga , Células Epiteliais/enzimologia , Células Epiteliais/metabolismo , Humanos , Hidroxilação , Pulmão/enzimologia , Pulmão/metabolismo , Nitrosaminas/metabolismo
4.
Sci Rep ; 6: 25300, 2016 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-27143125

RESUMO

Syndecan-4 (Syn4), a single-pass transmembrane heparin sulphate proteoglycan (HSPG), plays significant role in the formation of focal adhesions and interacts with many growth factors to regulate cell migration and neural induction. Here, we show the new roles of syndecan-4(syn4) in zebrafish embryonic neurogenesis. Syn4 is broadly and dynamically expressed throughout the early stages of embryonic development. Knockdown of syn4 increases the expression of the marker genes of multiple types of neural cells. The increased expression of the marker genes is resulted from excessive proliferation of the neural cells. In addition, disrupting syn4 expression results in truncated and multiple aberrant branching of caudal primary (CaP) axons. Collectively, these data indicate that Syn4 suppresses the cellular proliferation during neurogenesis and is crucial for the formation of CaP axons during zebrafish embryogenesis.


Assuntos
Proliferação de Células/efeitos dos fármacos , Neurogênese , Neurônios/fisiologia , Sindecana-4/metabolismo , Peixe-Zebra/embriologia , Animais , Expressão Gênica , Técnicas de Silenciamento de Genes , Técnicas de Inativação de Genes , Sindecana-4/genética
5.
Development ; 141(22): 4332-42, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25371367

RESUMO

Recently, emerging evidence has shown that Stat3 controls tumor cell migration and invasion. However, the molecular mechanisms by which Stat3 controls the cell movement remain largely unknown. Embryonic gastrula progenitors display coordinated and orientated migration, called collective cell migration. Collective cell migration is the simultaneous movement of multiple cells and is universally involved in physiological and pathological programs. Stat3 activity is required for the migration of gastrula progenitors, but it does not affect cell specification, thus suggesting that gastrula movements are an excellent model to provide insight into Stat3 control of cell migration in vivo. In this study, we reveal a novel mechanism by which Stat3 modulates extracellular matrix (ECM) assembly to control the coherence of collective migration of prechordal plate progenitors during zebrafish embryonic gastrulation. We show that Stat3 regulates the expression of Efemp2a in the prechordal plate progenitors that migrate anteriorly during gastrulation. Alteration of Stat3-Efemp2a signaling activity disrupted the configuration of fibronectin (FN) and laminin (LM) matrices, resulting in defective coherence of prechordal plate progenitor movements in zebrafish embryos. We demonstrate that Efemp2a acts as a downstream effector of Stat3 to promote ECM configuration for coherent collective cell migrations in vivo.


Assuntos
Movimento Celular/fisiologia , Endoderma/citologia , Proteínas da Matriz Extracelular/metabolismo , Matriz Extracelular/fisiologia , Gastrulação/fisiologia , Fator de Transcrição STAT3/metabolismo , Células-Tronco/fisiologia , Proteínas de Peixe-Zebra/metabolismo , Peixe-Zebra/embriologia , Adenoviridae , Animais , Imunoprecipitação da Cromatina , Clonagem Molecular , Primers do DNA/genética , Cães , Proteínas da Matriz Extracelular/genética , Imunofluorescência , Técnicas de Silenciamento de Genes , Células HeLa , Células Endoteliais da Veia Umbilical Humana , Humanos , Immunoblotting , Imunoprecipitação , Hibridização In Situ , Células Madin Darby de Rim Canino , Morfolinos/genética , Mutagênese , Fator de Transcrição STAT3/genética , Imagem com Lapso de Tempo , Peixe-Zebra/genética , Proteínas de Peixe-Zebra/genética
6.
Sci Rep ; 4: 5831, 2014 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-25060222

RESUMO

Normal interfollicular epidermis (IFE) homeostasis is maintained throughout the entire life by its own stem cells that self-renew and generate progeny that undergo terminal differentiation. However, the fine markers of the stem cells in interfollicular epidermis are not well defined yet. Here we found that TLR7 identified the existence of progenitors and interfollicular epidermal stem cells in murine skin. In vitro, TLR7-expressing cells comprised of two subpopulations that were competent to proliferate and exhibited distinct differentiation potentials. Three-dimensional (3D) organotypic culture and skin reconstitution assays showed that TLR7-expressing cells were able to reconstruct the interfollicular epidermis. Finally, TLR7-expressing cells maintained the intact interfollicular epidermal structures revealed in serial transplantation assays in vivo in mice. Taken together, our results suggest that TLR7-expressing cells comprise an interfollicular epidermal stem cell population.


Assuntos
Células Epidérmicas , Células-Tronco/citologia , Receptor 7 Toll-Like/metabolismo , Aminoquinolinas/farmacologia , Animais , Técnicas de Cultura de Células , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Epiderme/metabolismo , Epiderme/patologia , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Folículo Piloso/metabolismo , Imiquimode , Queratinócitos/citologia , Queratinócitos/efeitos dos fármacos , Queratinócitos/transplante , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Regeneração , Pele/metabolismo , Pele/patologia , Transplante de Células-Tronco , Células-Tronco/metabolismo , Engenharia Tecidual , Receptor 7 Toll-Like/agonistas , Receptor 7 Toll-Like/genética
7.
Sci Rep ; 4: 4470, 2014 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-24667151

RESUMO

The Snail family member snail encodes a zinc finger-containing transcriptional factor that is involved in heart formation. Yet, little is known about how Snail regulates heart development. Here, we identified that one of the duplicated snail genes, snai1b, was expressed in the heart region of zebrafish embryos. Depletion of Snai1b function dramatically reduced expression of α5 integrin, disrupted Fibronectin layer in the heart region, especially at the midline, and prevented migration of cardiac precursors, resulting in defects in cardiac morphology and function in zebrafish embryos. Injection of α5ß1 protein rescued the Fibronectin layer and then the myocardial precursor migration in snai1b knockdown embryos. The results provide the molecular mechanism how Snail controls the morphogenesis of heart during embryonic development.


Assuntos
Desenvolvimento Embrionário , Fibronectinas/metabolismo , Integrina alfa5/metabolismo , Fatores de Transcrição/genética , Proteínas de Peixe-Zebra/genética , Animais , Movimento Celular/genética , Embrião não Mamífero , Fibronectinas/genética , Coração/crescimento & desenvolvimento , Integrina alfa5/genética , Morfogênese/genética , Miocárdio/citologia , Fatores de Transcrição da Família Snail , Fatores de Transcrição/antagonistas & inibidores , Peixe-Zebra , Proteínas de Peixe-Zebra/antagonistas & inibidores
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA