Glutathione S-transferase pi in an arsenic-resistant Chinese hamster ovary cell line.
A glutathione S-transferase (GST) was purified from an arsenic-resistant Chinese hamster ovary cell line, SA7. The SA7 GST was shown to catalyse the conjugation of glutathione and ethacrynic acid, a specific substrate for Pi class GST. Its N-terminal amino-acid sequence has 80% identical residues to that of rat GST P and human GST pi. Thus, the GST purified from SA7 cells belongs to the Pi family. Treatment with Cibacron Blue or ethacrynic acid, which are GST inhibitors, significantly decreased the resistance of SA7 cells to sodium arsenite. On the other hand, pretreatment of SA7N cells, a partial revertant of SA7 cells, with sublethal doses of sodium arsenite, cadmium acetate or zinc sulphate resulted in re-elevation of GST activities and the cells regained the arsenic resistance. The regained arsenic resistance was well correlated with the levels of GST pi which were induced dose-dependently by zinc sulphate. Heat-shock treatment (45 degrees C for 10 min) did not increase GST pi expression or arsenic resistance of SA7N cells. The results indicate that GST pi is possibly involved in the mechanism of arsenic detoxification.
Lo
J F
JF
Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, Republic of China.
Wang
H F
HF
Tam
M F
MF
Lee
T C
TC
D000595:Amino Acid Sequence; D000818:Animals; D001151:Arsenic / Q000633:toxicity*; D018053:Arsenites; D016466:CHO Cells / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology; D006224:Cricetinae; D004351:Drug Resistance; D004591:Electrophoresis, Polyacrylamide Gel; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D006360:Heat-Shock Proteins / Q000096:biosynthesis; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D008668:Metallothionein / Q000378:metabolism; D008969:Molecular Sequence Data; D051381:Rats; D017670:Sodium Compounds; D013379:Substrate Specificity; D013431:Sulfates; D015032:Zinc; D019287:Zinc Sulfate
D018053:Arsenites; D006360:Heat-Shock Proteins; D007527:Isoenzymes; D017670:Sodium Compounds; D013431:Sulfates; C017947:sodium arsenite; D019287:Zinc Sulfate; D008668:Metallothionein; D005982:Glutathione Transferase; D015032:Zinc; D001151:Arsenic