出版社：American Society for Biochemistry and Molecular Biology
摘要：Serum amyloid A (SAA) is an amphiphilic helical protein thatis found associated with plasma HDL in various pathologicalconditions, such as acute or chronic inflammation. Cellularlipid 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 specificprofiles of cholesterol and phospholipid release. SAA mediatedcellular lipid release from these cells with the same profileas apoA-I. Upregulation of cellular ABCA1 protein by liver Xreceptor/retinoid X receptor agonists resulted in an increaseof cellular lipid release by apoA-I and SAA. SAA reacted withthe HEK293-derived clones that stably express human ABCA1 (293/2c)or ABCA7 (293/6c) to generate cholesterol-containing HDL ina similar manner to apoA-I. Dibutyryl cyclic AMP and phorbol12-myristate 13-acetate, which differentiate apoA-I-mediatedcellular lipid release between 293/2c and 293/6c, also exhibitedthe same differential effects on the SAA-mediated reactions.No evidence was found for the ABCA1/ABCA7-independent lipidrelease by SAA. Characterization of physicochemical propertiesof the HDL revealed that SAA-generated HDL particles had higherdensity, larger diameter, and slower electrophoretic mobilitythan those generated by apoA-I. These results demonstrate thatSAA generates cholesterol-containing HDL directly with cellularlipid 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
, tumor necrosis factor-
