Uncouplers of mitochondrial oxidative phosphorylation are not substrates of the erythrocyte glutathione-S-conjugate pump

Archives of Biochemistry and Biophysics
A Sokal, G Bartosz

Abstract

Uncouplers of mitochondrial oxidative phosphorylation, dinitrophenol (DNP) and carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP), were found to stimulate Mg(2+)-ATPase activity of human erythrocyte membranes in a manner competitive with respect to 2,4-dinitrophenyl-S-glutathione (DNP-SG) which suggested that these compounds may also be substrates of the glutathione-S-conjugate pump. We confirm that the stimulation of erythrocyte membrane ATPase activity by DNP and by another uncoupler, carbonyl cyanide m-chlorophenylhydrazone (CCCP), is competitive with respect to DNP-SG. However, we found no evidence for active transport of DNP and CCCP out of erythrocytes and demonstrate that they inhibit the low-affinity component of DNP-SG transport noncompetitively while stimulating the high-affinity DNP-SG transport (mediated by multidrug resistance-associated protein, MRP1). Implications of these findings may indicate the electrogenic nature of MRP1-mediated transport of glutathione-S conjugates and stimulation of aminophospholipid translocase (flippase) rather than the glutathione-S-conjugate pump by the uncouplers.

References

Nov 1, 1992·Trends in Biochemical Sciences·T Ishikawa
Jan 1, 1992·Annual Review of Biophysics and Biomolecular Structure·P F Devaux
Jun 15, 1990·Experientia·A Zachowski, P F Devaux
Jan 15, 1986·Biochemical Pharmacology·K G Eckert, P Eyer
Jan 1, 1967·Biochimica Et Biophysica Acta·P Wins, E Schoffeniels
Sep 21, 1995·Biochimica Et Biophysica Acta·L Pułaski, G Bartosz
Dec 1, 1994·Biochemical Medicine and Metabolic Biology·P KhannaS K Srivastava
Jan 15, 1993·The Biochemical Journal·C ChevillardA Cornish-Bowden
Jan 1, 1996·Annual Review of Pharmacology and Toxicology·W T Bellamy
Jun 1, 1996·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·D W LoeS P Cole
Nov 22, 1996·Biochemical Pharmacology·K Zhang, K P Wong

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Citations

Apr 23, 2009·The International Journal of Psycho-analysis·Charles Hanly

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