Some aspects of glutathione S-transferase P1-1 gene transcription regulation in human placenta

Abstract

Glutathione S-transferase P1-1 is the main phase II xenobiotic metabolism enzyme in human placenta. Low level of its gene expression and corresponding ineffective protection of fetus from toxic compounds is associated with pregnancy disorders such as preeclampsia and abnormalities of fetus development. It was previously reported that environmental radioactive contamination caused down-regulation of GSTP1 transcription in human placenta, but mechanisms responsible for such changes were unclear. In the present study we have found that observed changes in transcription of this gene are not caused by promoter methylation because GSTP1 promoter was not methylated in any of analyzed 91 placental samples. Regulation of GSTPl by methylation or transcription factors was not previously studied in human placenta. Using "Gene Expression Atlas" online software the placental expression profile of transcription factors known to interact with GSTP1 promoter in other cell types, was identified. According to computer analysis the genes coding for GATA2, GATA3, Fos-B, Nrf3 and MafK transcription factors are highly expressed in human placenta, while genes coding for c-Fos, Juns, Mafs, ERβ, RARα and NF-κB factors have moderate level of expression. Competitive EMSA provided the evidence that ARE and NF-κB-like sites specifically interacted with placental nuclear proteins. Among these proteins transcription factors AP-1 and NF-κB were identified using corresponding consensus oligonucleotides as competitors in EMSA