Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0008370 (
cholestasis
)
9,378
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The ATP-binding cassette (ABC) transporter A subfamily 8 (
ABCA8
) belongs to the ABCA6-like transporters subgroup, which is distinct from the ABCA1-like subgroup in the ABCA family. The expression and function of the short-size human
ABCA8
lacking one of the two ATP-binding domains for ATP hydrolysis, which are regularly present in the other ABCA transporters, have been reported. However, the functional differences between the short-size human
ABCA8
and full-size human
ABCA8
, which has the two ATP-binding domains, remain unknown. The purpose of the present study was to clarify the tissue expression profiles of ABCA6-like and ABCA1-like subgroup transporters and the functional characteristics of
ABCA8
in mouse and human. The tissue distribution of mouse ABCA (mABCA) transporter protein and the changes in mABCA8 protein expression levels in a mouse model of obstructive
cholestasis
were elucidated by means of quantitative targeted absolute proteomics (QTAP). The transport characteristics were clarified in a HEK293 cell line overexpressing full-size
ABCA8 protein
. QTAP and immunohistochemical analyses revealed that mABCA transporters exhibited the distinct protein expression patterns in the tissues, and mABCA8b, its mouse orthologue, was abundant in the liver and predominantly distributed in sinusoidal membranes of the hepatocytes. Further, protein expression of mABCA8b was decreased in the mouse
cholestasis
liver. Changes of mABCA8b expression level in
cholestasis
were similar to those of mABCA1, a sinusoidal cholesterol efflux transporter. Uptake and efflux assays showed that
ABCA8
mediates efflux of [
3
H]cholesterol and [
3
H]taurocholate, while it showed no significant efflux activity for [
3
H]estrone sulfate, [
3
H]digoxin, [
3
H]vinblastine, [
3
H]para-aminohippuric acid, [
3
H]oleic acid, [
14
C]nicotine, or [
3
H]methotrexate. [
3
H]Cholesterol efflux was increased by extracellularly applied taurocholate. These results suggest that mABCA8b/
ABCA8
functions as a sinusoidal efflux transporter for at least cholesterol and taurocholate in mouse and human liver.
...
PMID:ATP-Binding Cassette Transporter A Subfamily 8 Is a Sinusoidal Efflux Transporter for Cholesterol and Taurocholate in Mouse and Human Liver. 2930 Apr 88
