Barch D H, Rundhaugen L M, Pillay N S
Department of Medicine, Lakeside Veterans Affairs Medical Center, Chicago, IL.
Carcinogenesis. 1995 Mar;16(3):665-8. doi: 10.1093/carcin/16.3.665.
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.
谷胱甘肽S-转移酶(GST)的诱导可增强致癌物的解毒作用,并减少致癌物诱导的诱变和肿瘤发生。为了确定抗癌剂鞣花酸是否能诱导细胞内对致癌物进行解毒的酶,我们研究了鞣花酸对谷胱甘肽S-转移酶-Ya表达的影响。喂食鞣花酸的大鼠肝脏中总GST活性、肝脏GST-Ya活性和肝脏GST-Ya mRNA均显著增加。为了确定观察到的GST-Ya mRNA增加是否是由于鞣花酸诱导了GST-Ya基因的转录,我们用含有大鼠GST-Ya基因5'调控区不同部分的质粒构建体进行了转染研究。转染研究表明,鞣花酸通过诱导GST-Ya基因的转录增加了GST-Ya mRNA,并表明这种诱导是通过GST-Ya基因的抗氧化反应元件介导的。