The lipidation status of acute-phase protein serum amyloid A determines cholesterol mobilization via scavenger receptor class B, type I

Gunther Marsche , Sasa Frank , John G Raynes , Karen F Kozarsky , Wolfgang Sattler , Ernst Malle (1)

1 Medical University Graz

During the acute-phase reaction, serum amyloid A (SAA) replaces apoA-I as the major high-density lipoprotein (HDL)-associated apolipoprotein. A remarkable portion of SAA exists in a lipid-free/lipid-poor form and promotes ATP-binding cassette transporter A1 (ABCA1)-dependent cellular cholesterol efflux. In contrast to lipid-free apoA-I and apoE, lipid-free SAA was recently reported to mobilize scavenger receptor class B, type I (SR-BI)-dependent cellular cholesterol efflux (Van der Westhuyzen, D. R., Cai, L., de Beer, M. C., and de Beer, F. C. (2005) J. Biol. Chem. 280, 35890-35895). This unique property could strongly affect cellular cholesterol mobilization during inflammation. However, here we show that overexpression of SR-BI in HEK cells (devoid of ABCA1) failed to mobilize cholesterol to lipid-free or lipid-poor SAA. Only reconstituted vesicles containing phospholipids and SAA promoted SR-BI-mediated cholesterol efflux. Cholesterol efflux from HEK and HEK[SR-BI] cells to lipid-free and lipid-poor SAA was minimal while efficient efflux was observed from fibroblasts and CHO cells (both expressing functional ABCA1). Overexpression of SR-BI in CHO cells strongly attenuated cholesterol efflux to lipid-free SAA even in the presence of an SR-BI blocking IgG. This implies that SR-BI attenuates ABCA1-mediated cholesterol efflux in a way that is not dependent on SR-BI-mediated re-uptake of cholesterol. The present in vitro experiments demonstrate that the lipidation status of SAA is a critical factor governing cholesterol acceptor properties of this amphipathic apolipoprotein. In addition, we demonstrate that SAA mediates cellular cholesterol efflux via the ABCA1 and/or SR-BI pathway in a similar way as apoA-I.

Mots clés: Life Sciences

Gunther Marsche, Sasa Frank, John G Raynes, Karen F Kozarsky, Wolfgang Sattler, et al.. The lipidation status of acute-phase protein serum amyloid A determines cholesterol mobilization via scavenger receptor class B, type I. Biochemical Journal, 2006, 402 (1), pp.117-124. ⟨10.1042/BJ20061406⟩. ⟨hal-00478664⟩