Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 3 de 3
Filtrar
Mais filtros











Base de dados
Intervalo de ano de publicação
1.
Sci Rep ; 6: 35871, 2016 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-27767101

RESUMO

Sirtuin-1 (SIRT1) and SIRT6, NAD+-dependent Class III protein deacetylases, are putative anti-aging enzymes, down-regulated in patients with chronic obstructive pulmonary disease (COPD), which is characterized by the accelerated ageing of the lung and associated with increased oxidative stress. Here, we show that oxidative stress (hydrogen peroxide) selectively elevates microRNA-34a (miR-34a) but not the related miR-34b/c, with concomitant reduction of SIRT1/-6 in bronchial epithelial cells (BEAS2B), which was also observed in peripheral lung samples from patients with COPD. Over-expression of a miR-34a mimic caused a significant reduction in both mRNA and protein of SIRT1/-6, whereas inhibition of miR-34a (antagomir) increased these sirtuins. Induction of miR-34a expression with H2O2 was phosphoinositide-3-kinase (PI3K) dependent as it was associated with PI3Kα activation as well as phosphatase and tensin homolog (PTEN) reduction. Importantly, miR-34a antagomirs increased SIRT1/-6 mRNA levels, whilst decreasing markers of cellular senescence in airway epithelial cells from COPD patients, suggesting that this process is reversible. Other sirtuin isoforms were not affected by miR-34a. Our data indicate that miR-34a is induced by oxidative stress via PI3K signaling, and orchestrates ageing responses under oxidative stress, therefore highlighting miR-34a as a new therapeutic target and biomarker in COPD and other oxidative stress-driven aging diseases.


Assuntos
MicroRNAs/metabolismo , Estresse Oxidativo , Fosfatidilinositol 3-Quinases/metabolismo , Sirtuína 1/metabolismo , Sirtuínas/metabolismo , Regiões 3' não Traduzidas , Antagomirs/metabolismo , Linhagem Celular , Senescência Celular/efeitos dos fármacos , Proteínas de Ligação a DNA/metabolismo , Regulação para Baixo/efeitos dos fármacos , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Humanos , Peróxido de Hidrogênio/toxicidade , Pulmão/metabolismo , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Proteínas Nucleares/metabolismo , Estresse Oxidativo/efeitos dos fármacos , PTEN Fosfo-Hidrolase/metabolismo , Doença Pulmonar Obstrutiva Crônica/genética , Doença Pulmonar Obstrutiva Crônica/metabolismo , Doença Pulmonar Obstrutiva Crônica/patologia , RNA Mensageiro/química , RNA Mensageiro/metabolismo , Proteínas de Ligação a RNA/metabolismo , Sirtuína 1/genética , Sirtuínas/antagonistas & inibidores , Sirtuínas/genética , Escarro/metabolismo , Regulação para Cima/efeitos dos fármacos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA