Acidic phospholipids strikingly potentiate sterol carrier protein 2 mediated intermembrane sterol transfer.
A liposomal membrane model system was developed to examine the mechanism of spontaneous and protein-mediated intermembrane cholesterol transfer. Rat liver sterol carrier protein 2 (SCP2) and fatty acid binding protein (FABP, also called sterol carrier protein) both bind sterol. However, only SCP2 mediates sterol transfer. The exchange of sterol between small unilamellar vesicles (SUV) containing 35 mol % sterol was monitored with a recently developed assay [Nemecz, G., Fontaine, R. N., & Schroeder, F. (1988) Biochim. Biophys. Acta 943, 511-541], modified to continuous polarization measurement and not requiring separation of donor and acceptor membrane vesicles. As compared to spontaneous sterol exchange, 1.5 microM rat liver SCP2 enhanced the initial rate of sterol exchange between neutral zwwitterionic phosphatidylcholine SUV 2.3-fold. More important, the presence of acidic phospholipids (2.5-30 mol %) stimulated the SCP2-mediated increase in sterol transfer approximately 35-42-fold. Thus, acidic phospholipids strikingly potentiate the effect of SCP2 by 15-18 times as compared to SUV without negatively charged lipids. Rat liver FABP (up to 60 microM) was without effect on sterol transfer in either neutral zwitterionic or anionic phospholipid containing SUV. The potentiation of SCP2 action by acidic phospholipids was suppressed by high ionic strength, neomycin, and low pH. The results suggest that electrostatic interaction between SCP2 and negatively charged membranes may play an important role in the mechanism whereby SCP2 enhances intermembrane cholesterol transfer.
Butko
P
P
Department of Pharmacology and Medicinal Chemistry, College of Pharmacy, University of Cincinnati, Ohio 45267-0004.
Hapala
I
I
Scallen
T J
TJ
Schroeder
F
F
D002352:Carrier Proteins / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism*; D004875:Ergosterol / Q000031:analogs & derivatives / Q000378:metabolism; D005454:Fluorescence Polarization; D007526:Isoelectric Point; D007700:Kinetics; D008567:Membranes, Artificial; D010743:Phospholipids; D010940:Plant Proteins; D013261:Sterols / Q000378:metabolism*
D002352:Carrier Proteins; D008567:Membranes, Artificial; D010743:Phospholipids; D010940:Plant Proteins; D013261:Sterols; C072087:sterol carrier proteins; C010905:dehydroergosterol; D002784:Cholesterol; D004875:Ergosterol