1. Garlic organosulfur compounds upregulate the expression of the [pi] class of glutathione S-transferase in rat primary hepatocytes
- Author
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Tsai, Chia-Wen, Yang, Jaw-Ji, Chen, Haw-Wen, Sheen, Lee-Yan, and Lii, Chong-Kuei
- Subjects
Glutathione transferase -- Research ,Liver cells -- Research ,Organosulfur compounds -- Usage ,Organosulfur compounds -- Research ,Food/cooking/nutrition - Abstract
The chemopreventive property of garlic is related in part to its induction of phase II detoxification enzymes. In the present study, we investigated the modulatory effect of 3 garlic organosulfur compounds, i.e., diallyl sulfide (DAS), diallyl disulfide (DADS), and diallyl trisulfide (DATS), which differ in their number of sulfur atoms, on the gene expression of the [pi] class of glutathione S-transferase (GSTP). Hepatocytes isolated from male Sprague-Dawley rats were cultured with 50-200 [micro]mol/L of DAS, DADS, or DATS for 24 h. DADS and DATS increased GST activity toward ethacrynic acid by 40 and 66%, respectively (P < 0.05). Moreover, both garlic allyl sulfides dose dependently induced GSTP mRNA and protein expression. DATS increased the protein level more than DADS (P < 0.05). In contrast, DAS did not affect the activity or the protein or mRNA levels of this phase II drug-metabolizing enzyme. In Clone 9 liver cells, the pTA-luciferase reporter assay showed that luciferase activity in DADS- and DATS-treated cells was 2.8- and 3.9-fold higher than that in control cells, respectively (P < 0.05). Again, luciferase activity was not affected by treatment with DAS. Deletion of -2.7 to -2.6 kb in the GSTP promoter region, which contains the GSTP enhancer (GPE) I element, abolished the upregulation of GSTP transcription by DADS and DATS. Deletion of GPE II, however, did not affect the induction of reporter activity. In conclusion, the effectiveness of 3 garlic allyl sulfides on GSTP expression was related to the number of sulfur atoms in the molecules, and GPE I was responsible for this upregulation. KEY WORDS: * garlic organosulfur compounds * [pi] class of glutathione S-transferase * gene expression * hepatocytes * rats
- Published
- 2005