title: LDL receptor and ApoE are involved in the clearance of ApoM-associated sphingosine 1-phosphate.
abstract: Sphingosine 1-phosphate (S1P) is a vasoactive lipid mediator that is speculated to be involved in various aspects of atherosclerosis. About 70% of circulating plasma S1P is carried on HDL, and several pleiotropic properties of HDL have been ascribed to S1P. In the previous study with human subjects, however, LDL cholesterol or apoB, but not HDL cholesterol or apoA-I, had a significant positive correlation with the plasma S1P level, suggesting that the metabolic pathway for LDL might have some roles in the metabolism of S1P. In this study, we analyzed the association between LDL receptor, an important protein in the clearance of LDL, and circulating S1P. We observed that in LDL receptor-overexpressing mice, the plasma S1P levels as well as apolipoprotein M (apoM), a carrier of S1P, were decreased and that exogenously administered C17S1P bound to apoM-containing lipoproteins was cleared more rapidly. Unlike the situation in wild-type mice, LDL receptor overexpression in apoE-deficient mice did not reduce the plasma S1P or apoM levels, suggesting that apoE might be a ligand for the LDL receptor during the clearance of these factors. The present findings clarify the novel roles of the LDL receptor and apoE in the clearance of S1P, a multifunctional bioactive phospholipid.
authors.affiliation: From the Department of Clinical Laboratory Medicine, Graduate School of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655.
authors.forename: Makoto
authors.initials: M
authors.lastname: Kurano
authors.affiliation: the Department of Metabolism, Diabetes and Nephrology, Aizu Medical Center, Fukushima Medical University, 21-2, Maeda, Yazawaji, Higashimachi, Aizuwakamatsu, Fukushima 969-3482.
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Tsukamoto
authors.affiliation: the Department of Medicine IV, Mizonokuchi Hospital, Teikyo University School of Medicine, 3-8-3, Mizonokuchi, Takatsu-ku, Kawasaki, Kanagawa 213-0001, Japan.
authors.forename: Masumi
authors.initials: M
authors.lastname: Hara
authors.affiliation: the Department of Clinical Laboratory, University of Tokyo Hospital, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, and.
authors.forename: Ryunosuke
authors.initials: R
authors.lastname: Ohkawa
authors.affiliation: From the Department of Clinical Laboratory Medicine, Graduate School of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, the Department of Clinical Laboratory, University of Tokyo Hospital, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, and.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ikeda
authors.affiliation: From the Department of Clinical Laboratory Medicine, Graduate School of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, the Department of Clinical Laboratory, University of Tokyo Hospital, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, and yatoyuta-tky@umin.ac.jp.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yatomi
mesh_terms: D000818:Animals; D001053:Apolipoproteins / Q000378:metabolism*; D001057:Apolipoproteins E / Q000378:metabolism*; D000075243:Apolipoproteins M; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation; D056945:Hep G2 Cells; D006801:Humans; D008024:Ligands; D008099:Liver / Q000378:metabolism; D008246:Lysophospholipids / Q000097:blood*; D051379:Mice; D008810:Mice, Inbred C57BL; D011973:Receptors, LDL / Q000378:metabolism*; D012044:Regression Analysis; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000097:blood
chemical_list: C501623:ApoM protein, mouse; D001053:Apolipoproteins; D001057:Apolipoproteins E; D000075243:Apolipoproteins M; D008076:Cholesterol, HDL; D018076:DNA, Complementary; D008024:Ligands; D008246:Lysophospholipids; D011973:Receptors, LDL; C060506:sphingosine 1-phosphate; D002784:Cholesterol; D013110:Sphingosine
keywords: Apolipoprotein; Apolipoprotein E (ApoE); Lipoprotein Receptor; Low-density Lipoprotein (LDL); Sphingosine 1-Phosphate (S1P)