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001-es BibID:	BIBFORM039166
035-os BibID:	(scopus)0036272752 (wos)000175906900005
Első szerző:	Goda Katalin (biofizikus)
Cím:	Effects of ATP depletion and phosphate analogues on P-glycoprotein conformation in live cells / Goda, K., Nagy, H., Mechetner, E., Cianfriglia, M., Szabo, G.
Dátum:	2002
ISSN:	0014-2956
Megjegyzések:	P-glycoprotein (Pgp), a membrane pump often responsible for the multidrug resistance of cancer cells, undergoes conformational changes in the presence of substrates/modulators, or upon ATP depletion, reflected by its enhanced reactivity with the UIC2 monoclonal antibody. When the UIC2-shift was elicited by certain modulators (e.g. cyclosporin A or vinblastine, but not with verapamil or Tween 80), the subsequent binding of other monoclonal anti-Pgp Ig sharing epitopes with UIC2 (e.g. MM12.10) was abolished [Nagy, H., Goda, K., Arceci, R., Cianfriglia, M., Mechetner, E. & Szabó Jr, G. (2001) Eur. J. Biochem.268, 2416?2420]. To further study the relationship between UIC2-shift and the suppression of MM12.10 binding, we compared, on live cells, how ATP depletion and treatment of cells with phosphate analogues (sodium orthovanadate, beryllium fluoride and fluoro-aluminate) that trap nucleotides at the catalytic site, affect the two phenomena. Similarly to modulators or ATP depleting agents, all the phosphate analogues increased daunorubicin accumulation in Pgp-expressing cells. Prelabeling of ATP depleted cells with UIC2 completely abolished the subsequent binding of MM12.10, in accordance with the enhanced binding of the first mAb. Vanadate and beryllium fluoride, but not fluoro-aluminate, reversed the effect of cyclosporin A, preventing UIC2 binding and allowing for labeling of cells with MM12.10. Thus, changes in UIC2 reactivity are accompanied by complementary changes in MM12.10 binding also in response to direct modulation of the ATP-binding site, confirming that conformational changes intrinsic to the catalytic cycle are reflected by both UIC2-related phenomena. These data also fit a model where the UIC2 epitope is available for antibody binding throughout the catalytic cycle including the step of ATP binding, to become unavailable only in the catalytic transition state.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk
Megjelenés:	European Journal Of Biochemistry. - 269 : 11 (2002), p. 2672-2677. -
További szerzők:	Nagy Henrietta Mechetner, Eugene Cianfriglia, Maurizio Szabó Gábor (1953-) (biofizikus)
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001-es BibID:	BIBFORM004839
035-os BibID:	(WOS)000220105600025 (scopus)1342345242
Első szerző:	Nagy Henrietta
Cím:	Distinct groups of multidrug resistance modulating agents are distinguished by competition of P-glycoprotein-specific antibodies / Nagy, H., Goda, K., Fenyvesi, F., Bacso, Z., Szilasi, M., Kappelmayer, J., Lustyik, G., Cianfriglia, M., Szabo, G.
Dátum:	2004
Megjegyzések:	P-glycoprotein (Pgp) is one of the ABC transporters responsible for the multidrug resistance of cancer cells. The conformational changes of Pgp that occur in the presence of substrates/modulators or ATP depletion are accompanied by the up-shift of UIC2 monoclonal antibody (mAb) binding. In the case of cyclosporin A, vinblastine or valinomycin, this up-shift was found to be concomitant with the near-complete suppression of labeling with other mAbs specific for Pgp epitopes overlapping with UIC2, while pre-treatment with verapamil or Tween 80 brings about a modest suppression. Here we have extended these observations to 44 Pgp interacting agents, and found that only 8 fall into the cyclosporin-like category, inducing a conformational state characterized by the complete UIC2 dominance. The rest of the drugs either did not affect antibody competition or had a modest effect. Thus, Pgp substrates/modulators can be classified into distinct modalities based on the conformational change they elicit.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk Adenosine Adenosine Triphosphatases Animals Anti-Bacterial Agents Antibodies Antibodies,Monoclonal Antineoplastic Agents Binding,Competitive Biophysics Calcium Calcium Channel Blockers Cells Cyclosporine Detergents Drug Resistance,Multiple Drug Resistance,Neoplasm Epitopes Flow Cytometry Fluorescein Fluoresceins genetics Humans Hungary immunology Ivermectin metabolism Mice Nih 3T3 Cells P-Glycoprotein pharmacology physiology Research Substrate Specificity Support Valinomycin Verapamil Vinblastine egyetemen (Magyarországon) készült közlemény
Megjelenés:	Biochemical and Biophysical Research Communications. - 315 : 4 (2004), p. 942-949. -
További szerzők:	Goda Katalin (1969-) (biofizikus) Fenyvesi Ferenc (1977-) (gyógyszerész, gyógyszertechnológus) Bacsó Zsolt (1963-) (biofizikus) Szilasi Mária (1953-) (tüdőgyógyász, klinikai immunológus, allergológus, belgyógyász) Kappelmayer János (1960-) (laboratóriumi szakorvos) Lustyik György Cianfriglia, Maurizio Szabó Gábor (1953-) (biofizikus)
Internet cím:	elektronikus változat DOI
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