Ellagic acid induces transcription of the rat glutathione S-transferase-Ya gene

Abstract

Induction of glutathione S-transferase (GST) enzymes can increase detoxification of carcinogens and reduce carcinogen-induced mutagenesis and tumorigenesis. To determine if the anticarcinogen ellagic acid induces cellular enzymes which detoxify carcinogens, we examined the effect of ellagic acid on the expression of glutathione S-transferase-Ya. Rats fed ellagic acid demonstrated significant increases in total hepatic GST activity, hepatic GST-Ya activity and hepatic GST-Ya mRNA. To determine if the observed increase in GST-Ya mRNA was due to ellagic acid inducing transcription of the GST-Ya gene, transfection studies were performed with plasmid constructs containing various portions of the 5' regulatory region of the rat GST-Ya gene. The transfection studies demonstrated that ellagic acid increased GST-Ya mRNA by inducing transcription of the GST-Ya gene and demonstrated that this induction is mediated through the antioxidant responsive element of the GST-Ya gene.