ABSTRACT15-deoxy-delta 12,14-prostaglandin J2 (15d-PGJ2) is an anti-inflammatory/anti-neoplastic prostaglandin that functions through covalent binding to cysteine residues of various target proteins. We previously showed that 15d-PGJ2 mediated anti-inflammatory responses are dependent on the translational inhibition through its interaction with eIF4A (Kim et al., 2007). Binding of 15d-PGJ2 to eIF4A specifically blocks the interaction between eIF4G and eIF4A, which leads to the formation of stress granules (SGs), which then cluster mRNAs with inhibited translation. Here, we show that the binding between 15d-PGJ2 and eIF4A specifically blocks the interaction between the MIF4G domain of eIF4G and eIF4A. To reveal the mechanism of this interaction, we used computational simulation-based docking studies and identified that the carboxyl tail of 15d-PGJ2 could stabilize the binding of 15d-PGJ2 to eIF4A through arginine 295 of eIF4A, which is the first suggestion that the 15d-PGJ2 tail plays a physiological role. Interestingly, the putative 15d-PGJ2 binding site on eiF4A is conserved across many species, suggesting a biological role. Our data propose that studying 15d-PGJ2 and its targets may uncover new therapeutic approaches in anti-inflammatory drug discovery.
Simultaneous determination of amitraz, bromopropylate, coumaphos, cymiazole and 2,4-dimethylaniline in 200 honey samples purchased in Korea was performed by reversed-phase high-performance liquid chromatography with multiple UV detection. 2% Acetone in hexane was used for a liquid-liquid extraction and 20-40% water in acetonitrile solutions were used as mobile phases. The LOD for the analytes varied between 0.4 and 1.5 μg/L and the recoveries were yielded between 64 and 94%. Relative standard deviation of the repeatability of the method is less than 15%. Amitraz was not present in amount above 10 μg/L and one for coumaphos and cymiazole and two for bromopropylate, and three for 2,4-dimethylanilne were detected in amount above 10 μg/ L. Levels of the acaricide residues found were less than 50 μg/L.
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