Distinct groups of multidrug resistance modulating agents are distinguished by competition of P-glycoprotein-specific antibodies
| Autor: | János Kappelmayer, Zsolt Bacsó, Katalin Goda, György Lustyik, Maurizio Cianfriglia, Mária Szilasi, Gábor Szabó, Henrietta Nagy, Ferenc Fenyvesi |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Conformational change
medicine.drug_class Detergents Biophysics ATP-binding cassette transporter Antineoplastic Agents Monoclonal antibody Biochemistry Binding Competitive Epitope Substrate Specificity Mice Cyclosporin a polycyclic compounds medicine Animals Humans Elméleti orvostudományok ATP Binding Cassette Transporter Subfamily B Member 1 Molecular Biology P-glycoprotein Adenosine Triphosphatases Ivermectin integumentary system biology Antibodies Monoclonal Orvostudományok Cell Biology Calcium Channel Blockers Flow Cytometry Fluoresceins Drug Resistance Multiple Anti-Bacterial Agents Multiple drug resistance Drug Resistance Neoplasm biology.protein Cyclosporine NIH 3T3 Cells Antibody |
| Zdroj: | Biochemical and biophysical research communications. 315(4) |
| ISSN: | 0006-291X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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