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Chemical inhibitors destabilize HuR binding to the AU-rich element of TNF-alpha mRNA
Experimental & Molecular Medicine ; : 824-831, 2009.
Article in English | 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.
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Full text: Available Index: WPRIM (Western Pacific) Main subject: Protein Binding / Quercetin / Cell Line / Tumor Necrosis Factor-alpha / RNA-Binding Proteins / 3' Untranslated Regions / RNA Stability / Dose-Response Relationship, Drug / Drug Evaluation, Preclinical / Anti-Inflammatory Agents Type of study: Prognostic study Limits: Animals Language: English Journal: Experimental & Molecular Medicine Year: 2009 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Main subject: Protein Binding / Quercetin / Cell Line / Tumor Necrosis Factor-alpha / RNA-Binding Proteins / 3' Untranslated Regions / RNA Stability / Dose-Response Relationship, Drug / Drug Evaluation, Preclinical / Anti-Inflammatory Agents Type of study: Prognostic study Limits: Animals Language: English Journal: Experimental & Molecular Medicine Year: 2009 Type: Article