A Subregion of Reelin Suppresses Lipoprotein-Induced Cholesterol Accumulation in Macrophages

PloS One
Emmanuel U OkoroHong Yang

Abstract

Activation of apolipoprotein E receptor-2 (apoER2) and very low density lipoprotein receptor (VLDLR) inhibits foam cell formation. Reelin is a ligand of these receptors. Here we generated two reelin subregions containing the receptor binding domain with or without its C-terminal region (R5-6C and R5-6, respectively) and studied the impact of these peptides on macrophage cholesterol metabolism. We found that both R5-6C and R5-6 can be secreted by cells. Purified R5-6 protein can bind apoER2 and VLDLR. Overexpression of apoER2 in macrophages increased the amount of R5-6 bound to the cell surface. Treatment of macrophages with 0.2 μg/ml R5-6 elevated ATP binding cassette A1 (ABCA1) protein level by ~72% and apoAI-mediated cholesterol efflux by ~39%. In addition, the medium harvested from cells overexpressing R5-6 or R5-6C (R5-6- and R5-6C-conditioned media, respectively) also up-regulated ABCA1 protein expression, which was associated with accelerated cholesterol efflux and enhanced phosphorylation of phosphatidylinositol 3 kinase (PI3K) and specificity protein-1 (Sp1) in macrophages. The increased ABCA1 expression and cholesterol efflux by R5-6- and R5-6C-conditioned media were diminished by Sp1 or PI3K inhibitors mithramycin A a...Continue Reading

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Citations

Oct 16, 2016·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Elvira Khialeeva, Ellen M Carpenter
Oct 22, 2018·Neurogenetics·Júlia Canet-PonsUwe Warnken

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Datasets Mentioned

BETA
GM500

Methods Mentioned

BETA
ELISA
Assay
PCR
transfection

Software Mentioned

VassarStats

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