Hepatocellular transport in acquired cholestasis: new insights into functional, regulatory and therapeutic aspects

ROMA, MARCELO G.; CROCENZI, FERNANDO ARIEL; SÁNCHEZ POZZI, ENRIQUE J.

CLINICAL SCIENCE (LONDON, ENGLAND : 1979)

Biochemical Society

Lugar: Londres; Año: 2008 vol. 114 p. 567 - 588

0143-5221

The recent overwhelming advances in molecular and cell biology have added enormously to our   understanding of the physiological processes involved in bile formation and, by extension, to      our comprehension of the consequences of their alteration in cholestatic hepatopathies. The      present review addresses in detail this new information by summarizing a number of recent      experimental findings on the structural, functional and regulatory aspects of hepatocellular      transporter function in acquired cholestasis. This comprises (i) a short overview of the      physiological mechanisms of bile secretion, including the nature of the transporters involved and    their role in bile formation; (ii) the changes induced by nuclear receptors and hepatocyte-enriched transcription factors in the constitutive expression of hepatocellular transporters in cholestasis,      either explaining the primary biliary failure or resulting from a secondary adaptive response;      (iii) the post-transcriptional changes in transporter function and localization in cholestasis,      including a description of the subcellular structures putatively engaged in the endocytic      internalization of canalicular transporters and the involvement of signalling cascades in this effect;  and (iv) a discussion on how this new information has contributed to the understanding of the      mechanism by which anticholestatic agents exert their beneficial effects, or the manner in which     it has helped the design of new successful therapeutic approaches to cholestatic liver diseases.