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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)
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
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2.

001-es BibID:BIBFORM040018
Első szerző:Nagy Henrietta
Cím:P-Glycoprotein conformational changes detected by antibody competition / Nagy Henrietta, Goda Katalin, Arceci Robert, Cianfriglia Maurizio, Mechetner Eugene, Szabó Gábor jr.
Dátum:2001
ISSN:0014-2956
Megjegyzések:Conformational changes accompanying P-glycoprotein (Pgp) mediated drug transport are reflected by changes in the avidity of certain monoclonal antibodies (mAbs). More of the UIC2 mAb binds to Pgp-expressing cells in the presence of substrates or modulators [Mechetner, E.B., Schott, B., Morse, S.B., Stein, W., Druley, T., Dvis, K.A., Tsuruo, T. & Roninson, I.B. (1997) Proc. Natl Acad. Sci. USA 94, 12908-12913], while the binding of other mAbs (e.g. MM12.10, MRK16, 4E3) is not conformation sensitive. Pre-staining of Pgp+ cells with UIC2 decreased the subsequent binding of MM12.10 mAb by about 30-40%, suggesting that there are Pgp molecules available for both UIC2 and MM12.10, and others accessible only for MM12.10. In the presence of certain substrates/modulators such as vinblastin, cyclosporin A or valinomycin, the MM12.10 reactivity was completely abolished by preincubation with UIC2. However, verapamil, Tween-80 and nifedipine did not influence the ratio of bound mAbs significantly. This is the first assay to our knowledge, sharply distinguishing two classes of modulators. The conformational changes accompanying the mAb competition phenomenon appear to be closely related, though not identical to those accompanying the UIC2-shift, as suggested by the simultaneous assessment of the two phenomena.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
3T3 Cells
Animal
Antibiotics
Antibiotics,Peptide
Antibodies
Antibodies,Monoclonal
Antineoplastic Agents
Antineoplastic Agents,Phytogenic
Binding,Competitive
Biophysics
Calcium
Calcium Channel Blockers
Cells
chemistry
Cyclosporine
Drug Resistance,Neoplasm
Enzyme Inhibitors
Flow Cytometry
Human
Hungary
metabolism
Mice
Nifedipine
P-Glycoprotein
pharmacology
Polysorbates
Protein Binding
Protein Conformation
Substrate Specificity
Support,Non-U.S.Gov't
Tumor Cells,Cultured
Valinomycin
Verapamil
Vinblastine
Megjelenés:European Journal Of Biochemistry. - 268 : 8 (2001), p. 2416-2420. -
További szerzők:Goda Katalin (1969-) (biofizikus) Arceci, Robert Cianfriglia, Maurizio Mechetner, Eugene Szabó Gábor (1980-) (orvos) jr
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:
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