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Chemical inhibitors destabilize HuR binding to the AU-rich element of TNF-alpha mRNA

Cited 44 time in Web of Science Cited 47 time in Scopus
Authors
Chae, Min-Ju; Sung, Hye Youn; Kim, Eun-Hye; Lee, Mira; Chae, Chong Hak; Park, Woong-Yang; Kim, Sunwoo; Kwak, Hojoong
Issue Date
2009-11-30
Publisher
KOREAN SOC MED BIOCHEMISTRY MOLECULAR BIOLOGY
Citation
EXPERIMENTAL AND MOLECULAR MEDICINE; Vol.41 11; 824-831
Keywords
anti-inflammatory agentsELAV-Iike protein 1lipopolysaccharidestumor necrosis factor-alphaquercetinmacrophages
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 mu M. The IC(50) of quercetin, b-40, and b-41 were 1.4, 0.38, and 6.21 mu M, 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.
ISSN
1226-3613
Language
English
URI
http://hdl.handle.net/10371/78194
DOI
https://doi.org/10.3858/emm.2009.41.11.088
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College of Medicine/School of Medicine (의과대학/대학원)Dept. of Medicine (의학과)Journal Papers (저널논문_의학과)
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