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Journal of Lipid Research, Vol. 47, 1542-1550, July 2006
Copyright © 2006 by American Society for Biochemistry and Molecular Biology




* Biochemistry, Cell Biology, and Metabolism, Nagoya City University Graduate School of Medical Sciences, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan
Life Science Department, Nagoya City University Graduate School of Natural Sciences, Mizuho-cho, Mizuho-ku, Nagoya 467-8501, Japan
Department of Laboratory Medicine, Kochi University Medical School, Kohasu Okoh-cho, Nankoku, Kochi 783-8505, Japan
** Laboratory of Chemistry, College of Liberal Arts and Science, Tokyo Medical and Dental University, Ichikawa 272-0827, Japan

Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Kitashirakawa, Sakyo-ku, Kyoto 606-8502, Japan
Published, JLR Papers in Press, April 10, 2006.
1 To whom correspondence should be addressed. e-mail: syokoyam{at}med.nagoya-cu.ac.jp
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.
Abbreviations: apoA-I, apolipoprotein A-I; dBcAMP, dibutyryl cyclic AMP; DF medium, 1:1 mixture of Dulbecco's modified Eagle's medium and Ham's F12 medium; D-PBS, Dulbecco's phosphate-buffered saline; IL, interleukin; LPS, lipopolysaccharide; PMA, phorbol 12-myristate 13-acetate; SAA, serum amyloid A; SR-BI, scavenger receptor class B type I; TNF-
, tumor necrosis factor-
; TNFR-II, tumor necrosis factor receptor-II
Supplementary key words apolipoprotein cholesterol ATP binding cassette transporter A1 ATP binding cassette transporter A7
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