Perfluorodecanoic acid decreases the enzyme activity and the amount of glutathione S-transferases proteins and mRNAs in vivo

Abstract

The effects of the anti-wetting agent perfluoro- n-decanoic acid (PFDA) on various glutathione S-transferase (GST) enzyme activities were studied in vitro and in vivo. In addition the effects of PFDA treatment on the amount of some glutathione S-transferase subunits and their corresponding translatable mRNA were studied in vivo. PFDA like some other peroxisome proliferators was a non-competitive inhibitor of several GST enzyme activities in vitro. In vivo PFDA reduced the enzyme activity towards substrates which are indicative for the Ya, Yb 1 and Yb 2 subunits of GSTs to a larger extent than the enzyme activity towards the substrate indicative for the Yc subunit. Whereas the reduction of GST enzyme activities by other peroxisome proliferators was shown to be caused by an inhibition of the relevant enzymes in vivo, PFDA was found to decrease the GST enzyme activities at least in part by lowering the amount of the various GST subunits in vivo due to a lowered concentration of translatable mRNA coding for these enzymes. In addition PFDA abolished the inducibility of GST mRNAs by phenobarbital. Thus PFDA might be an interesting tool for mechanistic studies of the control of GST expression in the liver.