24(S)-hydroxycholesterol is actively eliminated from neuronal cells by ABCA1.
High cholesterol turnover catalyzed by cholesterol 24-hydroxylase is essential for neural functions, especially learning. Because 24(S)-hydroxycholesterol (24-OHC), produced by 24-hydroxylase, induces apoptosis of neuronal cells, it is vital to eliminate it rapidly from cells. Here, using differentiated SH-SY5Y neuron-like cells as a model, we examined whether 24-OHC is actively eliminated via transporters induced by its accumulation. The expression of ABCA1 and ABCG1 was induced by 24-OHC, as well as TO901317 and retinoic acid, which are ligands of the nuclear receptors LXR/RXR. When the expression of ABCA1 and ABCG1 was induced, 24-OHC efflux was stimulated in the presence of high density lipoprotein (HDL), whereas apolipoprotein A-I was not an efficient acceptor. The efflux was suppressed by the addition of siRNA against ABCA1, but not by ABCG1 siRNA. To confirm the role of each transporter, we analyzed HEK293 cells stably expressing human ABCA1 or ABCG1; we clearly observed 24-OHC efflux in the presence of HDL, whereas efflux in the presence of apolipoprotein A-I was marginal. Furthermore, the treatment of primary cerebral neurons with LXR/RXR ligands suppressed the toxicity of 24-OHC. These results suggest that ABCA1 actively eliminates 24-OHC in the presence of HDL as a lipid acceptor and protects neuronal cells. This article is protected by copyright. All rights reserved.
T10 T11 T12 T13 T14 T15 T16 T17 T18 T19 T1 T20 T21 T22 T23 T24 T25 T26 T27 T28 T29 T2 T30 T31 T32 T33 T34 T35 T36 T37 T3 T4 T5 T6 T7 T8 T9
CHEMICAL CHEMICAL CHEMICAL CHEMICAL GENE-N GENE-Y GENE-N GENE-N GENE-Y GENE-N CHEMICAL GENE-Y GENE-Y GENE-N GENE-Y GENE-Y GENE-N GENE-N GENE-N GENE-Y GENE-Y CHEMICAL GENE-N GENE-N GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL
retinoic acid 24-OHC 24-OHC 24(S)-hydroxycholesterol HDL apolipoprotein A-I LXR RXR ABCA1 HDL 24-OHC 24-hydroxylase cholesterol 24-hydroxylase transporters ABCA1 ABCG1 nuclear receptors LXR RXR ABCA1 ABCG1 24-OHC high density lipoprotein HDL apolipoprotein A-I ABCA1 ABCG1 human ABCA1 ABCG1 ABCA1 24(S)-hydroxycholesterol 24-OHC 24-OHC cholesterol 24-OHC TO901317 cholesterol