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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Inhibition of the efflux of glutathione S-conjugates by plant polyphenols.

The formation of dinitrophenylglutathione (DNP-SG) in human colon adenocarcinoma cells was identified and quantified by an HPLC-UV method, following exposure to 1-chloro-2,4-dinitrobenzene (CDNB) at 10 degrees for 40 min. The rate of efflux of DNP-SG at 37 degrees likewise, was measured by monitoring the DNP-SG content in the extracellular medium. Among the polyphenols examined for their action on DNP-SG export, butein was the most potent inhibitor with an IC50 value of 15 microM. The others, in order of decreasing potencies, were quercetin, tannic acid, 2'-hydroxychalcone, 2-hydroxychalcone anIIC50 values in the micromolar range. These polyphenols did not affect the ATP or the glutathione content of the cells. Mg(2+)-ATPase extracted from the plasma membrane of the cells was activated by DNP-SG in a concentration-dependent manner, and the reaction showed saturation kinetics with K(m) and Vmax values of 110 microM and 12.3 nmol/min/mg protein, respectively. However, the six polyphenols mentioned above had negligible effects on the Mg(2+)-ATPase activity, suggesting that this was probably not the target of their inhibitory action. Probenecid, p-trifluoromethoxy-phenylhydrazone (FCCP) and chlorambucil also showed varying degrees of inhibition of the export of DNP-SG.[1]

References

  1. Inhibition of the efflux of glutathione S-conjugates by plant polyphenols. Zhang, K., Wong, K.P. Biochem. Pharmacol. (1996) [Pubmed]
 
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