INVESTIGADORES
SANCHEZ POZZI Enrique Juan
artículos
Título:
Hepatocellular transport in acquired cholestasis: new insights into functional, regulatory and therapeutic aspects
Autor/es:
ROMA, MARCELO; CROCENZI, FERNANDO; SANCHEZ POZZI, EJ
Revista:
CLINICAL SCIENCE (LONDON, ENGLAND : 1979)
Editorial:
Portland Press
Referencias:
Lugar: Londres; Año: 2008 vol. 114 p. 567 - 588
ISSN:
0143-5221
Resumen:
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.