Selective expression of glutathione S-transferase genes in the murine gastrointestinal tract in response to dietary organosulfur compounds

A short-term feeding regimen was designed to analyze the effects of compounds such as diallyl disulfide (DADS), diallylthiosulfinate (allicin) from garlic and butylated hydroxyanisole (BHA) on glutathione S-transferase (GST) expression in the gastrointestinal tract and liver of male mice. After animals were force-fed these compounds, tissue GSTs were purified and individual subunits resolved by HPLC and identified on the basis of mass spectrometry (ESI MS) and immunoreactivity data. The effects of DADS and allicin on GST expression were especially prominent in stomach and small intestine, where there were major coordinate changes in GST subunit profiles. In particular, the transcripts of the mGSTM1 and mGSTM4 genes, which share large segments of common 5′-flanking sequences, and their corresponding subunits were selectively induced. Levels of α class subunits also increased, whereas mGSTM3 and mGSTP1 were not affected. The inducible mGSTA5 and non-responsive mGSTM3 subunits had not been identified previously. Liver and colon GSTs were also affected to a lesser extent, but this short-term feeding regimen had no effect on GST subunit patterns from other organs, including heart, brain and testis. Real-time PCR (TagMan) methods were used for quantitative estimations of relative amounts of the mRNAs encoding the GSTs. Effects on the transcripts generally paralleled changes at the protein level, for the most part, however, the greatest relative increases were observed for those mRNAs that were expressed at low abundance constituitively. Mechanisms by which the organosulfur compounds operate to affect GST transcription could involve reversible modification of certain protein sulfhydryl groups, shifts in reduced glutathione/oxidized glutathione ratios and resultant changes in cellular redox status.