Novel Mechanism of Cholesterol Transport by ABCA5 in Macrophages and Its Role in Dyslipidemia.
ATP Binding Cassette Transporter 1
/ chemistry
ATP-Binding Cassette Transporters
/ chemistry
Adult
Animals
Cholesterol
/ blood
Diet, High-Fat
/ adverse effects
Disease Models, Animal
Dyslipidemias
/ chemically induced
Female
Humans
Macrophages
/ metabolism
Male
Mice
Middle Aged
Models, Molecular
Protein Conformation
RAW 264.7 Cells
THP-1 Cells
ABC transporter
atherosclerosis
cholesterol homeostasis
macrophages
reverse cholesterol transport
Journal
Journal of molecular biology
ISSN: 1089-8638
Titre abrégé: J Mol Biol
Pays: Netherlands
ID NLM: 2985088R
Informations de publication
Date de publication:
07 08 2020
07 08 2020
Historique:
received:
06
06
2020
revised:
02
07
2020
accepted:
10
07
2020
pubmed:
21
7
2020
medline:
26
1
2021
entrez:
21
7
2020
Statut:
ppublish
Résumé
Cholesterol homeostasis results from a delicate interplay between influx and efflux of free cholesterol primarily mediated by ABCA1. Here we report downregulation of ABCA1 in hyper-cholesterol conditions in macrophages, which might be responsible for compromised reverse cholesterol transport and hyperlipidemia. Surprisingly, this is countered by the upregulation of a lesser known family member ABCA5 to maintain cholesterol efflux. The relative contribution of ABCA1 and ABCA5 toward cholesterol efflux was evaluated and revealed ABCA5 as the primary efflux mediator under high cholesterol load. These observations were correlated to cholesterol load in circulation in vivo, and we observed an inverse expression profile in mice models of atherosclerosis (ApoE
Identifiants
pubmed: 32687853
pii: S0022-2836(20)30450-2
doi: 10.1016/j.jmb.2020.07.006
pii:
doi:
Substances chimiques
ABCA1 protein, human
0
ABCA5 protein, human
0
ATP Binding Cassette Transporter 1
0
ATP-Binding Cassette Transporters
0
Cholesterol
97C5T2UQ7J
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4922-4941Informations de copyright
Copyright © 2020 Elsevier Ltd. All rights reserved.