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24(S)‐hydroxycholesterol is actively eliminated from neuronal cells by ABCA 1
Author(s) -
Matsuda Akihiro,
Nagao Kohjiro,
Matsuo Michinori,
Kioka Noriyuki,
Ueda Kazumitsu
Publication year - 2013
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.12275
Subject(s) - chemistry , microbiology and biotechnology , neuroscience , biology
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 ‐ SY 5Y neuron‐like cells as a model, we examined whether 24‐ OHC is actively eliminated via transporters induced by its accumulation. The expression of ABCA 1 and ABCG 1 was induced by 24‐ OHC , as well as TO 901317 and retinoic acid, which are ligands of the nuclear receptors liver X receptor/retinoid X receptor ( LXR / RXR ). When the expression of ABCA 1 and ABCG 1 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 si RNA against ABCA 1, but not by ABCG 1 si RNA . To confirm the role of each transporter, we analyzed human embryonic kidney 293 cells stably expressing human ABCA 1 or ABCG 1; 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 ABCA 1 actively eliminates 24‐ OHC in the presence of HDL as a lipid acceptor and protects neuronal cells.