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.
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May 2008
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Review Article|
April 02 2008
Hepatocellular transport in acquired cholestasis: new insights into functional, regulatory and therapeutic aspects
Marcelo G. Roma;
1Instituto de Fisiología Experimental (IFISE), Facultad de Ciencias Bioquímicas y Farmacéuticas (CONICET–U.N.R.), Suipacha 570, S2002LRL, Rosario, Argentina
Correspondence: Dr. Marcelo G. Roma (email [email protected]).
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Fernando A. Crocenzi;
Fernando A. Crocenzi
1Instituto de Fisiología Experimental (IFISE), Facultad de Ciencias Bioquímicas y Farmacéuticas (CONICET–U.N.R.), Suipacha 570, S2002LRL, Rosario, Argentina
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Enrique A. Sánchez Pozzi
Enrique A. Sánchez Pozzi
1Instituto de Fisiología Experimental (IFISE), Facultad de Ciencias Bioquímicas y Farmacéuticas (CONICET–U.N.R.), Suipacha 570, S2002LRL, Rosario, Argentina
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Publisher: Portland Press Ltd
Received:
July 03 2007
Revision Received:
October 30 2007
Accepted:
November 07 2007
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2008 Biochemical Society
2008
Clin Sci (Lond) (2008) 114 (9): 567–588.
Article history
Received:
July 03 2007
Revision Received:
October 30 2007
Accepted:
November 07 2007
Citation
Marcelo G. Roma, Fernando A. Crocenzi, Enrique A. Sánchez Pozzi; Hepatocellular transport in acquired cholestasis: new insights into functional, regulatory and therapeutic aspects. Clin Sci (Lond) 1 May 2008; 114 (9): 567–588. doi: https://doi.org/10.1042/CS20070227
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