RGD Reference Report - Estradiol-17beta-D-glucuronide induces endocytic internalization of Bsep in rats. - Rat Genome Database

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Estradiol-17beta-D-glucuronide induces endocytic internalization of Bsep in rats.

Authors: Crocenzi, FA  Mottino, AD  Cao, J  Veggi, LM  Pozzi, EJ  Vore, M  Coleman, R  Roma, MG 
Citation: Crocenzi FA, etal., Am J Physiol Gastrointest Liver Physiol. 2003 Aug;285(2):G449-59. Epub 2003 Apr 17.
RGD ID: 1598571
Pubmed: PMID:12702498   (View Abstract at PubMed)
DOI: DOI:10.1152/ajpgi.00508.2002   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cholestasis  ISOAbcb11 (Rattus norvegicus)1598571; 1598571 RGD 
cholestasis  ISOAbcc2 (Rattus norvegicus)1598571; 1598571 RGD 
cholestasis  IDA 1598571 RGD 
cholestasis  IAGP 1598571 RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
response to estrogen  IEP 1598571 RGD 
response to estrogen  IDA 1598571 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Abcb11  (ATP binding cassette subfamily B member 11)
Abcc2  (ATP binding cassette subfamily C member 2)

Genes (Mus musculus)
Abcb11  (ATP-binding cassette, sub-family B member 11)
Abcc2  (ATP-binding cassette, sub-family member 2)

Genes (Homo sapiens)
ABCB11  (ATP binding cassette subfamily B member 11)
ABCC2  (ATP binding cassette subfamily C member 2)


Additional Information