ATP binding cassette G1-dependent cholesterol efflux during inflammation.
ATP binding cassette transporter G1 (ABCG1) mediates the transport of cellular cholesterol to HDL, and it plays a key role in maintaining macrophage cholesterol homeostasis. During inflammation, HDL undergoes substantial remodeling, acquiring lipid changes and serum amyloid A (SAA) as a major apolipoprotein. In the current study, we investigated whether remodeling of HDL that occurs during acute inflammation impacts ABCG1-dependent efflux. Our data indicate that lipid free SAA acts similarly to apolipoprotein A-I (apoA-I) in mediating sequential efflux from ABCA1 and ABCG1. Compared with normal mouse HDL, acute phase (AP) mouse HDL containing SAA exhibited a modest but significant 17% increase in ABCG1-dependent efflux. Interestingly, AP HDL isolated from mice lacking SAA (SAAKO mice) was even more effective in promoting ABCG1 efflux. Hydrolysis with Group IIA secretory phospholipase A(2) (sPLA(2)-IIA) significantly reduced the ability of AP HDL from SAAKO mice to serve as a substrate for ABCG1-mediated cholesterol transfer, indicating that phospholipid (PL) enrichment, and not the presence of SAA, is responsible for alterations in efflux. AP human HDL, which is not PL-enriched, was somewhat less effective in mediating ABCG1-dependent efflux compared with normal human HDL. Our data indicate that inflammatory remodeling of HDL impacts ABCG1-dependent efflux independent of SAA.
Departments of Physiology, University of Kentucky Medical Center, Lexington, KY, USA. mdebeer@uky.edu
Maria C
MC
de Beer
Ailing
A
Ji
Anisa
A
Jahangiri
Ashley M
AM
Vaughan
Frederick C
FC
de Beer
Deneys R
DR
van der Westhuyzen
Nancy R
NR
Webb
D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000210:Acute-Phase Reaction / Q000503:physiopathology*; D000818:Animals; D016632:Apolipoprotein A-I / Q000378:metabolism; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D006224:Cricetinae; D006801:Humans; D008074:Lipoproteins / Q000378:metabolism*; D008075:Lipoproteins, HDL / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D000685:Serum Amyloid A Protein / Q000378:metabolism*
C487540:ABCG1 protein, mouse; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D016632:Apolipoprotein A-I; D008074:Lipoproteins; D008075:Lipoproteins, HDL; D000685:Serum Amyloid A Protein; D002784:Cholesterol