Genomic cloning and characterization of the rat glutathione S-transferase-A3-subunit gene

Abstract

The rat glutathione S-transferase-A3-subunit (GSTA3) gene is a member of the class Alpha GSTs, which we have previously reported to be overexpressed in anti-cancer-drug-resistant cells. In this study, we report the isolation and characterization of the entire rat GSTA3 (rGST Yc " ) subunit gene. The rat GSTA3 subunit gene is approximately 15 kb in length and consists of seven exons interrupted by introns of different lengths. Exon 1, with a length of 219 bp, contains only the 5h-untranslated region of the gene. Each exon-intron splicing junction exhibited the consensus sequence for a mammalian splice site. The transcription start site and exon 1 of rat GSTA3 were characterized by a combination of primer extension and rapid amplification of the cDNA ends. Position j1 was identified 219 bp upstream of the first exon-intron splicing junction. The proximal promoter region of the rat GSTA3 subunit gene does not contain typical TATA or CAAT boxes. A computer-based search for potential transcription-factor binding sites revealed the existence of a

Expression of the Aflatoxin B1-8,9-Epoxide-Metabolizing Murine GlutathioneS-Transferase A3 Subunit Is Regulated by the Nrf2 Transcription Factor through an Antioxidant Response Element

“…The in vivo role of Nrf2 in regulating mGSTA3 expression in lung and throughout the gastrointestinal tract (targets of AFB 1 toxicity) has been revealed through analysis of tissue samples derived from either wild-type or nrf2 Ϫ/Ϫ mice. Most class ␣ GST genes in human, rat, and mouse have been shown to comprise seven exons, with the first being a noncoding exon (Daniel et al, 1987;Rohrdanz et al, 1992;Rozen et al, 1992;Fotouhi-Ardakani and Batist, 1999). Together, these observations suggest that the ancestral gene structure of class ␣ GST has been conserved.…”

“…As such, exon 1 encodes only 5Ј-untranslated sequence. These gross aspects of genomic organization are conserved in genes encoding other class ␣ GST (Daniel et al, 1987;Rohrdanz et al, 1992;Rozen et al, 1992;Fotouhi-Ardakani and Batist, 1999). A more detailed comparison was made between the mGSTA3 gene and the previously described rat GSTA3 (rGSTA3) gene (Fig.…”

The combined effects of garlic oil and fish oil on the hepatic antioxidant and drug-metabolizing enzymes of rats

“…GST and many CYP enzymes have been shown to be inducible in the presence of various drugs and food components (Vos & Van Bladeren, 1990;Guengerich, 1995). The molecular mechanisms involved in the regulation of GST isoenzyme genes are mediated by an antioxidant-responsive element and the activator protein-1-responsive element; both are located on GST gene promoter and/or enhancer regions (Rushmore & Pickett, 1990;Bergelson et al 1994;Fotouhi-Ardakani & Batist, 1999). However, the molecular mechanism of garlic's effect is not clear and it is compelling to investigate whether GO mediates GST genes through the antioxidant-responsive element pathway and/or the Fos/Jun binding to AP-1 binding site.…”

A novel role of glutathione S-transferase A3 in inhibiting hepatic stellate cell activation and rat hepatic fibrosis

“…GSTA3 is a special member of the α-GST subfamily. The antioxidant response elements in the proximal promoter region of the GSTA3 gene are involved in its antioxidant activity [24]. Indeed, oxidative damage is aggravated in GSTA3 knockout mice following exposure to CCl 4 [16].…”