Up-regulation of transporters of the MRP family by drugs and toxins

Toxicol Lett. 2001 Mar 31;120(1-3):51-7. doi: 10.1016/s0378-4274(01)00306-x.

Abstract

Expression of a variety of ABC efflux pumps including certain conjugate transporters of the multidrug resistance protein (MRP) subfamily is inducible in primate and rodent tissues, and in a variety of cell lines and primary cells in culture. In human cell lines (HepG2, MCF-7), we studied the inducibility of MRPs 1-5. Similar to the rat mrp2 gene, human mrp2 is inducible by the chemical carcinogen 2-AAF, the chemotherapeutic drug cisplatin and the barbiturate phenobarbital, as demonstrated in Northern and Western Blots. Furthermore, the antibiotic rifampicin was identified as MRP2 inducer in HepG2 cells. MRP1 and 4 mRNAs being expressed in human liver at a very low level could not be detected in HepG2 cells after treatment with various agents. However, MRP3 and 5 mRNAs were detected in addition to MRP2 and their expression was found to be increased by 2-AAF, cisplatin and rifampicin. MRP1 expression was studied in MCF-7 cells where the chemotherapeutic drug vinblastine and tert-butyl hydroquinone but not the MRP2 inducing agents described above acted as inducers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B / genetics*
  • ATP-Binding Cassette Transporters / genetics*
  • Animals
  • Anion Transport Proteins
  • Carrier Proteins / genetics*
  • Gene Expression Regulation / drug effects*
  • Humans
  • Membrane Transport Proteins*
  • Multidrug Resistance-Associated Protein 2
  • Multidrug Resistance-Associated Proteins
  • Toxins, Biological / toxicity*
  • Up-Regulation

Substances

  • ABCC2 protein, human
  • ABCC5 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • ATP-Binding Cassette Transporters
  • Abcc5 protein, rat
  • Anion Transport Proteins
  • Carrier Proteins
  • Membrane Transport Proteins
  • Multidrug Resistance-Associated Protein 2
  • Multidrug Resistance-Associated Proteins
  • Toxins, Biological
  • multidrug resistance-associated protein 1