Structural organization of the human gastrointestinal glutathione peroxidase (GPX2) promoter and 3 '-nontranscribed region: transcriptional response to exogenous redox agents

The flanking upstream and downstream regions of the human GPX2 gene were is olated and sequenced. Analysis of the flanking 5'-nontranslated or promoter region revealed a high homology with the corresponding murine region (> 70 %). The human GPX2 promoter region was not G-C rich (< 50% G + C) and class ical TATA/CCAAT elements were not present. The ubiquitous SP1 and AP elemen ts were present. Several GATA elements as well as liver-specific sites (HNF series) were present. Despite the unique intestinal specific expression of GPX2, classical intestine-specific sites were not detected in the flanking 5' or 3' regions. The ability of the GPX2 promoter to direct transcription was confirmed. Exogenous agents capable of producing oxidative stress, suc h as paraquat, could induce the transcriptional activity of the GPX2 promot er. Analysis of three previously reported polymorphism sites revealed that they represented the most common polymorphisms. Surprisingly, the human GPX 2 promoter could direct transcription and respond to oxidative stress in th e murine NIH3T3 fibroblast cell line, which is devoid of the ability to bin d to a variety of intestinal specific elements. This finding suggests that the unique intestinal specific expression of GPX2 may be due to elements in the intron, the flanking 3'-nontranslated region, or to elements existing even farther upstream. The ability of GPX2 to respond transcriptionally to redox stress is likely to be more physiologically relevant than post-transc riptional regulation which is dependent upon selenium availability. (C) 200 0 Elsevier Science B.V. All rights reserved.