INVESTIGADORES
SANCHEZ POZZI Enrique Juan
artículos
Título:
Estradiol-17ß-D-glucuronide induces endocytic internalization of BSEP in the rat.
Autor/es:
CROCENZI, FERNANDO A; MOTTINO, ALDO D; CAO, J; VEGGI, LUIS M; ENRIQUE JUAN SANCHEZ POZZI; VORE, MARY; ROGER COLEMAN,; ROMA, MARCELO G
Revista:
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
Editorial:
AMER PHYSIOLOGICAL SOC
Referencias:
Lugar: Bethesda; Año: 2003 vol. 285 p. 1 - 1
ISSN:
0193-1857
Resumen:
Endocytic internalization of the multidrug resistance-associated protein
2 (Mrp2) was previously suggested to be involved in
estradiol-17beta-D-glucuronide (E217G)-induced cholestasis. Here we
evaluated in the rat whether a similar phenomenon occurs with the bile
salt export pump (Bsep) and the ability of DBcAMP to prevent it. E217G
(15 micromol/kg i.v.) impaired bile salt (BS) output and induced Bsep
internalization, as assessed by confocal microscopy and Western
blotting. Neither cholestasis nor Bsep internalization occurred in TR-
rats lacking Mrp2. DBcAMP (20 micromol/kg i.v.) partially prevented the
decrease in bile flow and BS output and substantially prevented
E217G-induced Bsep internalization. In hepatocyte couplets, E217G (50
microM) diminished canalicular accumulation of a fluorescent BS and
decreased Bsep-associated fluorescence in the canalicular membrane;
DBcAMP (10 microM) fully prevented both effects. In conclusion, our
results suggest that changes in Bsep localization are involved in
E217G-induced impairment of bile flow and BS transport and that DBcAMP
prevents this effect by stimulating insertion of canalicular
transporter-containing vesicles. Mrp2 is required for E217G to induce
its harmful effect.