Serum amyloid A is a ligand for scavenger receptor class B type I and inhibits high density lipoprotein binding and selective lipid uptake.
Serum amyloid A is an acute phase protein that is carried in the plasma largely as an apolipoprotein of high density lipoprotein (HDL). In this study we investigated whether SAA is a ligand for the HDL receptor, scavenger receptor class B type I (SR-BI), and how SAA may influence SR-BI-mediated HDL binding and selective cholesteryl ester uptake. Studies using Chinese hamster ovary cells expressing SR-BI showed that (125)I-labeled SAA, both in lipid-free form and in reconstituted HDL particles, functions as a high affinity ligand for SR-BI. SAA also bound with high affinity to the hepatocyte cell line, HepG2. Alexa-labeled SAA was shown by fluorescence confocal microscopy to be internalized by cells in a SR-BI-dependent manner. To assess how SAA association with HDL influences HDL interaction with SR-BI, SAA-containing HDL was isolated from mice overexpressing SAA through adenoviral gene transfer. SAA presence on HDL had little effect on HDL binding to SR-BI but decreased (30-50%) selective cholesteryl ester uptake. Lipid-free SAA, unlike lipid-free apoA-I, was an effective inhibitor of both SR-BI-dependent binding and selective cholesteryl ester uptake of HDL. We have concluded that SR-BI plays a key role in SAA metabolism through its ability to interact with and internalize SAA and, further, that SAA influences HDL cholesterol metabolism through its inhibitory effects on SR-BI-mediated selective lipid uptake.
Cai
Lei
L
Department of Internal Medicine, Graduate Center for Nutritional Sciences, University of Kentucky Medical Center, Lexington, Kentucky 40536, USA.
de Beer
Maria C
MC
de Beer
Frederick C
FC
van der Westhuyzen
Deneys R
DR
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D018955:CD36 Antigens; D016466:CHO Cells; D002460:Cell Line; D002788:Cholesterol Esters / Q000378:metabolism; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D018014:Gene Transfer Techniques; D006801:Humans; D008024:Ligands; D050356:Lipid Metabolism; D008075:Lipoproteins, HDL / Q000378:metabolism*; D051379:Mice; D018613:Microscopy, Confocal; D011485:Protein Binding; D020033:Protein Isoforms; D011971:Receptors, Immunologic / Q000378:metabolism / Q000502:physiology*; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B; D000685:Serum Amyloid A Protein / Q000096:biosynthesis*; D013696:Temperature; D013997:Time Factors
D018955:CD36 Antigens; D002788:Cholesterol Esters; D008024:Ligands; D008075:Lipoproteins, HDL; D020033:Protein Isoforms; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B; D000685:Serum Amyloid A Protein