Chemical inhibitors destabilize HuR binding to the AU-rich element of TNF-alpha mRNA
Experimental & Molecular Medicine
;
: 824-831, 2009.
Artigo
em Inglês
| WPRIM
| ID: wpr-174318
ABSTRACT
Hu protein R (HuR) binds to the AU-rich element (ARE) in the 3'UTR to stabilize TNF-alpha mRNA. Here, we identified chemical inhibitors of the interaction between HuR and the ARE of TNF-alpha mRNA using RNA electrophoretic mobility gel shift assay (EMSA) and filter binding assay. Of 179 chemicals screened, we identified three with a half-maximal inhibitory concentration (IC(50)) below 10 micrometer. The IC(50) of quercetin, b-40, and b-41 were 1.4, 0.38, and 6.21 micrometer, respectively, for binding of HuR protein to TNF-alpha mRNA. Quercetin and b-40 did not inhibit binding of tristetraprolin to the ARE of TNF-alpha mRNA. When LPS-treated RAW264.7 cells were treated with quercetin and b-40, we observed decreased stability of TNF-alpha mRNA and decreased levels of secreted TNF-alpha. From these results, we could find inhibitors for the TNF-alpha mRNA stability, which might be used advantageously for both the study for post-transcriptional regulation and the discovery of new anti-inflammation drugs.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Ligação Proteica
/
Quercetina
/
Linhagem Celular
/
Fator de Necrose Tumoral alfa
/
Proteínas de Ligação a RNA
/
Regiões 3' não Traduzidas
/
Estabilidade de RNA
/
Relação Dose-Resposta a Droga
/
Avaliação Pré-Clínica de Medicamentos
/
Anti-Inflamatórios
Tipo de estudo:
Estudo prognóstico
Limite:
Animais
Idioma:
Inglês
Revista:
Experimental & Molecular Medicine
Ano de publicação:
2009
Tipo de documento:
Artigo
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