Glutathione S-transferase pi facilitates the excretion of arsenic from arsenic-resistant Chinese hamster ovary cells.
We have previously demonstrated that glutathione S-transferase pi (GST pi) is overexpressed in SA7 cells, an arsenic resistant cell line derived from Chinese hamster ovary (CHO) cells. Our present results show that SA7 cells accumulate less arsenic than parental CHO cells and partially revertant SA7N cells. The lower levels of arsenic accumulation in SA7 cells resulted from their faster excretion rates. However, the excretion of arsenic from SA7 cells was significantly inhibited by the GST inhibitors ethacrynic acid and Cibacron blue. Furthermore, when GST pi levels in SA7N cells were re-elevated by zinc sulfate pretreatment, arsenic accumulation decreased and arsenic excretion increased to levels similar to those in SA7 cells. These results suggest that GST pi can facilitate the excretion of arsenic. Such facilitation by GST pi is unlikely to be associated with multi-drug resistant P-glycoprotein, since no overexpression of P-glycoprotein was detected in SA7N and SA7 cells.
Wang
H F
HF
Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, Republic of China.
Lee
T C
TC
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000818:Animals; D001151:Arsenic / Q000378:metabolism* / Q000494:pharmacology*; D001692:Biological Transport; D015153:Blotting, Western; D016466:CHO Cells; D002352:Carrier Proteins / Q000302:isolation & purification / Q000378:metabolism; D002999:Clone Cells; D006224:Cricetinae; D004351:Drug Resistance / Q000502:physiology*; D004976:Ethacrynic Acid / Q000494:pharmacology; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000302:isolation & purification / Q000378:metabolism; D013431:Sulfates / Q000494:pharmacology; D013997:Time Factors; D014227:Triazines / Q000494:pharmacology; D015032:Zinc / Q000494:pharmacology; D019287:Zinc Sulfate
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002352:Carrier Proteins; D007527:Isoenzymes; D008562:Membrane Glycoproteins; D013431:Sulfates; D014227:Triazines; C012842:Cibacron Blue F 3GA; D019287:Zinc Sulfate; D005982:Glutathione Transferase; D015032:Zinc; D004976:Ethacrynic Acid; D001151:Arsenic