An evaluation of the mechanism of ABCA7 on cellular lipid release in ABCA7-HEC293 cell.
- Author:
Cheng-Ai WU
1
;
Na WANG
;
Dan-Hui ZHAO
Author Information
- Publication Type:Journal Article
- MeSH: ATP Binding Cassette Transporter 1; analysis; genetics; physiology; ATP-Binding Cassette Transporters; analysis; genetics; physiology; Amino Acid Sequence; Apolipoprotein A-I; physiology; Gene Expression Regulation; HEK293 Cells; Humans; Hydrocarbons, Fluorinated; pharmacology; Hydroxycholesterols; pharmacology; Lipid Metabolism; Liver X Receptors; Molecular Sequence Data; Orphan Nuclear Receptors; agonists; Sulfonamides; pharmacology
- From: Chinese Medical Journal 2013;126(2):306-310
- CountryChina
- Language:English
-
Abstract:
BACKGROUNDABCA7 is a member of the ABCA subfamily that shows a high degree of homology to ABCA1 and, like ABCA1, mediates cellular cholesterol and phospholipid release by apolipoproteins when transfected in vitro. However, expression of ABCA7 has been shown to be downregulated by increased cellular cholesterol while ABCA1 was upregulated.
METHODSThe underlying mechanism for this effect was examined in ABCA1 or ABCA7-transfected HEC293. Lipid content in the medium and cells was determined by enzymatic assays. Gene expression was quantitated by real time PCR, and protein content was determined by Western blotting.
RESULTSWhile ABCA7 mRNA was decreased by 25-hydroxycholesterol treatment, ABCA1 was apparently increased. Treatment with the synthetic LXR agonist T0901317 (T09) upregulated ABCA1 expression and apoAI-mediated cellular lipid release in ABCA1-transfected HEC293 cells, but ABCA7 expression and cellular lipid release in ABCA7-transfected HEC293 cells showed no obvious changes.
CONCLUSIONThe ABCA7 gene is regulated by sterol in a direction opposite to that of ABCA1.