title: Critical role of ABCA1 transporter in sphingosine 1-phosphate release from astrocytes.
abstract: Sphingosine 1-phosphate (S1P) is accumulated in lipoproteins, especially high-density lipoprotein (HDL), in plasma. However, it remains uncharacterized how extracellular S1P is produced in the CNS. The treatment of rat astrocytes with retinoic acid and dibutyryl cAMP, which induce apolipoprotein E (apoE) synthesis and HDL-like lipoprotein formation, stimulated extracellular S1P accumulation in the presence of its precursor sphingosine. The released S1P was present together with apoE particles in the HDL fraction. S1P release from astrocytes was inhibited by the treatment of the cells with glybenclamide or small interfering RNAs specific to ATP-binding cassette transporter A1 (ABCA1). Astrocytes from Abca1-/- mice also showed impairment of retinoic acid/dibutyryl cAMP-induced S1P release in association with the blockage of HDL-like lipoprotein formation. However, the formation of either apoE or lipoprotein itself was not sufficient, and additional up-regulation of ABCA1 was requisite to stimulate S1P release. We conclude that the S1P release from astrocytes is coupled with lipoprotein formation through ABCA1.
authors.affiliation: Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Japan. kosato@showa.gunma-u.ac.jp
authors.forename: Koichi
authors.initials: K
authors.lastname: Sato
authors.forename: Enkhzol
authors.initials: E
authors.lastname: Malchinkhuu
authors.forename: Yuta
authors.initials: Y
authors.lastname: Horiuchi
authors.forename: Chihiro
authors.initials: C
authors.lastname: Mogi
authors.forename: Hideaki
authors.initials: H
authors.lastname: Tomura
authors.forename: Masahiko
authors.initials: M
authors.lastname: Tosaka
authors.forename: Yuhei
authors.initials: Y
authors.lastname: Yoshimoto
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kuwabara
authors.forename: Fumikazu
authors.initials: F
authors.lastname: Okajima
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000502:physiology*; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001057:Apolipoproteins E / Q000096:biosynthesis; D001253:Astrocytes / Q000378:metabolism*; D015153:Blotting, Western; D003994:Bucladesine / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D005822:Genetic Vectors; D008074:Lipoproteins / Q000096:biosynthesis; D008075:Lipoproteins, HDL / Q000096:biosynthesis; D008246:Lysophospholipids / Q000378:metabolism*; D051379:Mice; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D013268:Stimulation, Chemical; D014212:Tretinoin / Q000494:pharmacology
chemical_list: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D001057:Apolipoproteins E; D017077:Culture Media, Conditioned; D008074:Lipoproteins; D008075:Lipoproteins, HDL; D008246:Lysophospholipids; C060506:sphingosine 1-phosphate; D014212:Tretinoin; D003994:Bucladesine; D013110:Sphingosine