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001-es BibID:	BIBFORM046298
Első szerző:	Goda Katalin (biofizikus)
Cím:	Reversal of Multidrug Resistance by Valinomycin is Overcome by CCCP / Goda K., Krasznai Z., Gaspar R., Lankelma J., Westerhoff H. V., Damjanovich S., Szabo G.
Dátum:	1996
ISSN:	0006-291X
Megjegyzések:	Reversal of P-glycoprotein-mediated multidrug resistance by valinomycin is overcome by the proton ionophore, CCCP. This effect, a complete suppression of the 5- to 10-fold valinomycin-induced reversal ("re-reversal"), exhibits a sharp extracellular potassium concentration ([K+(0)]) dependence. It is observed at [K+(0)] > 2-4 mM and not at [K+(0)] greater than or equal to 2 mM, in the case of the fluorescent substrates rhodamine 123 and daunorubicin. The fact that "re-reversal" is detected only for the combination of CCCP with valinomycin raises the possibility that a direct interaction between these ionophores may explain the phenomenon. We show spectroscopic evidence of such an interaction, with a [K+(0)]-dependence similar to that of the "re-reversal." These data suggest that the reversal of P-glycoprotein activity by valinomycin can be compromised by anionic compounds such as CCCP due to complex formation. More generally, molecular interactions involving P-glycoprotein substrates or reversing agents may significantly affect drug accumulation in multidrug resistant cells.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:	Biochemical And Biophysical Research Communications. - 219 : 2 (1996), p. 306-310. -
További szerzők:	Krasznai Zoltán (1950-) (biofizikus) Gáspár Rezső (1944-) (biofizikus) Lankelma, Jan Westerhoff, Hans V. Damjanovich Sándor (1936-2017) (biofizikus) Szabó Gábor (1953-) (biofizikus)
Pályázati támogatás:	T14655 OTKA 17592 OTKA
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
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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
Internet cím:	Intézményi repozitóriumban (DEA) tárolt változat DOI Szerző által megadott URL
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