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001-es BibID:	BIBFORM004945
Első szerző:	Heijn, Marc
Cím:	Anthracyclines modulate multidrug resistance protein (MRP) mediated organic anion transport / Marc Heijn, Jan H. Hooijberg, George L. Scheffer, Gábor Szabó, Hans V. Westerhoff, Jan Lankelma
Dátum:	1997
ISSN:	0005-2736
Megjegyzések:	We studied the ATP-dependent uptake of dinitrophenyl-glutathione (GS-DNP) into plasma membrane vesicles derived from parental GLC4 cells and from multidrug resistant GLC4/ADR cells. The latter have a high expression of the multidrug resistance protein (MRP). Uptake of GS-DNP into membrane vesicles from GLC4/ADR cells was highly stimulated by the addition of ATP, compared to the uptake into membrane vesicles from GLC4 cells. This ATP-dependent uptake into membrane vesicles from GLC4/ADR cells was saturable with a Km of 1.2 +/- 0.2 microM and a Vmax of 560 +/- 80 pmol/mg prot./min. ATP stimulated GS-DNP uptake with a Km of 187 +/- 4 microM. This uptake was specifically inhibited by a polyclonal serum raised against a fusion protein containing a segment of MRP. The ATP-dependent uptake of GS-DNP was not only inhibited by organic anions, such as oxidized glutathione (GSSG), methotrexate (MTX) and some bile acids, but also by non-anionic natural product drugs, such as anthracyclines, vinca alkaloids and etoposide (VP-16). Uptake of GSSG and MTX into membrane vesicles from GLC4/ADR cells could be stimulated by ATP. The ATP-dependent uptake of GSSG had a Km of 43 +/- 3 microM and a Vmax of 900 +/- 200 nmol/mg protein/min. The ATP-dependent uptake of GS-DNP seemed to be non-competitively inhibited by the anthracycline daunorubicin (DNR), whereas the ATP-dependent GSSG uptake seemed to be competitively inhibited by DNR. A substrate binding site on MRP is proposed that comprises a pocket in which both DNR and GS-DNP or GSSG bind in random order to different, only partly overlapping sites. In this pocket binding of a second compound is influenced by the compound which was bound first.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban Drug resistance, multiple Biological transport Adenosine triphosphate Kinetics Glutathione/aa Daunorubicin
Megjelenés:	Biochimica et Biophysica Acta (BBA). Biomembranes. - 1326 : 1 (1997), p. 12-22. -
További szerzők:	Hooijberg, Jan H. Scheffer, George L. Szabó Gábor (1953-) (biofizikus) Westerhoff, Hans V. Lankelma, Jan
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