Regulation of hepatic ABCC transporters by xenobiotics and in disease states

Drug Metab Rev. 2010 Aug;42(3):482-538. doi: 10.3109/03602531003654915.

Abstract

The subfamily of ABCC transporters consists of 13 members in mammals, including the multidrug resistance-associated proteins (MRPs), sulfonylurea receptors (SURs), and the cystic fibrosis transmembrane conductance regulator (CFTR). These proteins play roles in chemical detoxification, disposition, and normal cell physiology. ABCC transporters are expressed differentially in the liver and are regulated at the transcription and translation level. Their expression and function are also controlled by post-translational modification and membrane-trafficking events. These processes are tightly regulated. Information about alterations in the expression of hepatobiliary ABCC transporters could provide important insights into the pathogenesis of diseases and disposition of xenobiotics. In this review, we describe the regulation of hepatic ABCC transporters in humans and rodents by a variety of xenobiotics, under disease states and in genetically modified animal models deficient in transcription factors, transporters, and cell-signaling molecules.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Cholestasis / genetics
  • Cholestasis / metabolism
  • Fatty Liver / genetics
  • Fatty Liver / metabolism
  • Gene Expression Regulation
  • Humans
  • Liver Circulation / physiology
  • Liver Diseases / genetics
  • Liver Diseases / metabolism*
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism
  • Mice
  • Multidrug Resistance-Associated Proteins / biosynthesis
  • Multidrug Resistance-Associated Proteins / genetics
  • Multidrug Resistance-Associated Proteins / metabolism*
  • Rats
  • Xenobiotics / pharmacology*

Substances

  • Multidrug Resistance-Associated Proteins
  • Xenobiotics
  • multidrug resistance-associated protein 2
  • multidrug resistance-associated protein 1