Subcellular Localization and Activity of the Multidrug Resistance Protein 1

<p>Multi-drug resistance or MDR is a major impediment to the successful administration of chemotherapy. Broadly defined, the term MDR applies to any mechanism the cell uses to counter the effects of chemotherapeutic agents, protecting the cell at once against the toxicity of many, structurally dissimilar compounds. There are several routes to MDR for a cell, and they include everything from decreasing intracellular drug concentrations to increasing rates drug metabolism. The study presented here focuses on the role of drug transporters in conferring drug resistance. MDR transporters are traditionally thought to extrude cytotoxins from the cell at the plasma membrane, and they thereby serve as a permeability barrier for drug entry into the cell. Several MDR transporters have been cloned to date, but this study focuses on the functional characterization of one of these proteins, the human multidrug resistance protein or MRP1. MRP1, like other members of the MDR transporter family, is thought to be expressed at the plasma membrane and decrease the intracellular accumulation of many different chemotherapeutic compounds. Unlike other MDR transporters, however, MRP1 is thought to require reduced glutathione to enable the transport of most of its chemotherapeutic substrates. Using a fluourescently tagged MRP1 protein, we make two novel demonstrations: that MRP1 can contribute to a drug resistance phenotype from intracellular membranes, as well as from the plasma membrane; and two, that MRP1 is active in the absence of glutathione.</p>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Thesis

Year

2003

Author dc:creator

• Rajagopal, Asha

Contributors dc:contributor

• Sanford M. Simon

• multi-drug resistance (MDR)
• MRP1
• drug transporters
• chemotherapy
• intracellular membranes
• glutathione-independent activity
• Life Sciences

Repository record dc:identifier

https://digitalcommons.rockefeller.edu/student_theses_and_dissertations/327

OAI identifier oai:identifier

oai:digitalcommons.rockefeller.edu:student_theses_and_dissertations-1326