Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 2 de 2
Filtrar
Mais filtros











Base de dados
Intervalo de ano de publicação
1.
Genet Mol Res ; 16(2)2017 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-28510254

RESUMO

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects motor neurons and lacks an effective treatment. The disease pathogenesis has not been clarified at present. Pathological transactive response DNA-binding protein 43 (TDP-43) plays an important role in the pathogenesis of ALS. Nuclear translocation of nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2) is found in a mutant TDP-43 transgenic cell model, but its downstream antioxidant enzyme expression is decreased. To elucidate the specific mechanism of Nrf2/ARE (antioxidant responsive element) signaling dysfunction, we constructed an ALS cell model with human mutant TDP-43 using the NSC-34 cell line to evaluate the impact of the TDP-43 mutation on the Nrf2/ARE pathway. We found the nuclear translocation of Nrf2, but the expression of total Nrf2, cytoplasmic Nrf2, and downstream phase II detoxifying enzyme (NQO1) was decreased in NSC-34 cells transfected with the TDP-43-M337V plasmid. Besides, TDP-43-M337V plasmid-transfected NSC-34 cells were rounded with reduced neurites, shortened axons, increased levels of intracellular lipid peroxidation products, and decreased viability, which suggests that the TDP-43-M337V plasmid weakened the antioxidant capacity of NSC-34 cells and increased their susceptibility to oxidative damage. We further showed that expression of the MafK protein and the Jun dimerization protein 2 (JDP2) was reduced in TDP-43-M337V plasmid-transfected NSC-34 cells, which might cause accumulation of Nrf2 in nuclei but a decrease in NQO1 expression. Taken together, our results confirmed that TDP-43-M337V impaired the Nrf2/ARE pathway by reducing the expression of MafK and JDP2 proteins, and provided information for further research on the molecular mechanisms of TDP-43-M337V in ALS.


Assuntos
Esclerose Lateral Amiotrófica/metabolismo , Proteínas de Ligação a DNA/metabolismo , Fator de Transcrição MafK/metabolismo , Mutação de Sentido Incorreto , Fator 2 Relacionado a NF-E2/metabolismo , Proteínas Repressoras/metabolismo , Elementos de Resposta , Animais , Linhagem Celular , Proteínas de Ligação a DNA/genética , Fator de Transcrição MafK/genética , Camundongos , NAD(P)H Desidrogenase (Quinona)/metabolismo , Neurônios/metabolismo , Estresse Oxidativo , Proteínas Repressoras/genética
2.
Genet Mol Res ; 14(3): 7315-25, 2015 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-26214410

RESUMO

Osteosarcoma is one of the most common primary bone tumors in children and young adults. In this study, we investigated the role of musculoaponeurotic fibrosarcoma oncogene homolog K (MAFK) in osteosarcoma cell proliferation in vitro and the possible pathways that contributed to MAFK-related osteosarcoma development. We first reported that MAFK was expressed at low levels in an osteosarcoma cell line. Furthermore, a significant correlation between MAFK and the Wnt signaling pathway was observed in osteosarcoma by using a gene microarray assay. We found that expression of MAFK could be induced by Wnt1 in a dose-dependent manner. Furthermore, Wnt1-induced MAFK expression caused a significant increase of cell viability, whereas a Wnt pathway inhibitor, IWR-1-endo, abolished Wnt1-induced effects on MAFK. Finally, cell cycle analysis showed that enhanced cell proliferation might be attributed to re-distribution of the cell cycle. Together, our results suggested that Wnt1-induced MAFK expression promoted cell proliferation in MG63 cells, and that the role of MAFK in osteosarcoma might be closely linked to the Wnt signaling pathway.


Assuntos
Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Fator de Transcrição MafK/biossíntese , Osteossarcoma/metabolismo , Osteossarcoma/patologia , Proteína Wnt1/metabolismo , Neoplasias Ósseas/genética , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Humanos , Fator de Transcrição MafK/genética , Osteossarcoma/genética , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Transfecção , Via de Sinalização Wnt , Proteína Wnt1/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA