title: Serum amyloid A generates high density lipoprotein with cellular lipid in an ABCA1- or ABCA7-dependent manner.
abstract: Serum amyloid A (SAA) is an amphiphilic helical protein that is found associated with plasma HDL in various pathological conditions, such as acute or chronic inflammation. Cellular lipid release and generation of HDL by this protein were investigated, in comparison with the reactions by apolipoprotein A-I (apoA-I) and several types of cells that appear with various specific profiles of cholesterol and phospholipid release. SAA mediated cellular lipid release from these cells with the same profile as apoA-I. Upregulation of cellular ABCA1 protein by liver X receptor/retinoid X receptor agonists resulted in an increase of cellular lipid release by apoA-I and SAA. SAA reacted with the HEK293-derived clones that stably express human ABCA1 (293/2c) or ABCA7 (293/6c) to generate cholesterol-containing HDL in a similar manner to apoA-I. Dibutyryl cyclic AMP and phorbol 12-myristate 13-acetate, which differentiate apoA-I-mediated cellular lipid release between 293/2c and 293/6c, also exhibited the same differential effects on the SAA-mediated reactions. No evidence was found for the ABCA1/ABCA7-independent lipid release by SAA. Characterization of physicochemical properties of the HDL revealed that SAA-generated HDL particles had higher density, larger diameter, and slower electrophoretic mobility than those generated by apoA-I. These results demonstrate that SAA generates cholesterol-containing HDL directly with cellular lipid and that the reaction is mediated by ABCA1 and ABCA7.
authors.affiliation: Biochemistry, Cell Biology, and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan.
authors.forename: Sumiko
authors.initials: S
authors.lastname: Abe-Dohmae
authors.forename: Koichi H
authors.initials: KH
authors.lastname: Kato
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Kumon
authors.forename: Wei
authors.initials: W
authors.lastname: Hu
authors.forename: Hideaki
authors.initials: H
authors.lastname: Ishigami
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Iwamoto
authors.forename: Mitsuyo
authors.initials: M
authors.lastname: Okazaki
authors.forename: Chen-Ai
authors.initials: CA
authors.lastname: Wu
authors.forename: Maki
authors.initials: M
authors.lastname: Tsujita
authors.forename: Kazumitsu
authors.initials: K
authors.lastname: Ueda
authors.forename: Shinji
authors.initials: S
authors.lastname: Yokoyama
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D016466:CHO Cells; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism; D006224:Cricetinae; D006801:Humans; D066298:In Vitro Techniques; D050356:Lipid Metabolism; D008075:Lipoproteins, HDL / Q000096:biosynthesis* / Q000737:chemistry; D051379:Mice; D010316:Particle Size; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D000685:Serum Amyloid A Protein / Q000378:metabolism*; D014162:Transfection
chemical_list: C577836:ABCA1 protein, human; C411895:ABCA7 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D008075:Lipoproteins, HDL; D011994:Recombinant Proteins; D000685:Serum Amyloid A Protein; D002784:Cholesterol