Regulation of hepatic ABCC transporters by xenobiotics and in disease states

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.

Keywords::

• ABCC transporters
• multidrug resistance-associated protein (MRP)
• sulfonylurea receptor (SUR)
• cystic fibrosis transmembrane conductance regulator (CFTR)
• xenobiotics
• gene regulation
• liver diseases

Acknowledgements

JEM is the Marlene L. Cohen and Jerome H. Fleisch Scholar in the Department of Pharmaceutical Sciences at the University of Connecticut (Storrs, Connecticut, USA).

Declaration of interest

XG, postdoctoral fellow in JEM’s laboratory, has been supported by the National Institutes of Health (Bethesda,Maryland, USA) (grant DK069557). The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.