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The interaction of selected natural products with human recombinant glutathione transferases
Author(s) -
Hayeshi Rose,
Mukanganyama Stanley,
Hazra Banasri,
Abegaz Berhanu,
Hasler Julia
Publication year - 2004
Publication title -
phytotherapy research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.019
H-Index - 129
eISSN - 1099-1573
pISSN - 0951-418X
DOI - 10.1002/ptr.1481
Subject(s) - ergothioneine , glutathione , biochemistry , chemistry , recombinant dna , enzyme , ic50 , in vivo , non competitive inhibition , in vitro , antioxidant , biology , gene , microbiology and biotechnology
The interaction of geshoidin, diospyrin and ergothioneine, with heterologously expressed human glutathione transferases (GSTs) was investigated in vitro . Diospyrin and geshoidin inhibited the three GST isoforms tested, with IC 50 values in the range 0.1–0.5 µ m , whereas ergothioneine had no effect on the GSTs. The predominant mode of inhibition was noncompetitive with respect to both glutathione (GSH) and 1‐chloro‐2,4‐dinitrobenzene (CDNB). Diospyrin, however, competitively inhibited A1‐1 and M1‐1 with respect to GSH and geshoidin displayed mixed inhibition toward A1‐1 with respect to GSH. The K i values for diospyrin with respect to both GSH and CDNB were in the range 0.08–0.6 µM and those for geshoidin were in the range 16–173 µM. These results indicate that diospyrin is a potent inhibitor of heterologously expressed human GSTs A1‐1, M1‐1 and P1‐1. Diospyrin and geshoidin were also found to inactivate P1‐1 with diospyrin being a potent inactivator. Given these inhibitory properties, diospyrin may be a potential GST chemomodulator. Ergothioneine inactivated P1‐1 only after preincubation and it enhanced ethacrynic acid inactivation of P1‐1. Inactivation of P1‐1 by ergothioneine may have implications for the antioxidant roles of P1‐1 and ergothioneine in vivo . Copyright © 2004 John Wiley & Sons, Ltd.