Redistribution of Membrane Raft Microdomains by Apolipoprotein A-I In Mouse Aortic Endothelial Cells.

Abstract

Apolipoprotein A-I (apoAI) upregulates ATP-binding cassette transport A1 (ABCA1) in various cell types. ABCA1 has been shown to induce the redistribution of raft-associated proteins and lipids to the non-raft membrane. This report investigated the effect of apoAI on ABCA1 expression and raft cholesterol and protein distribution, as well as the effect of ABCA1 knockdown on apoAI-induced changes in mouse aortic endothelial cells (MAECs). Our data demonstrated that ABCA1 was distributed in both the lipid raft and non-raft membranes and was coimmunoprecipitated with caveolin-1 (CAV1). ApoAI treatment significantly increased the mRNA and protein levels of ABCA1 and reduced the percentage of ABCA1 in the raft membrane. Our data also showed that free cholesterol (FC) and CAV1 were concentrated in the raft-like detergent-resistant membranes (DRMs) under the control conditions. ApoAI treatment did not alter the cellular level of FC and CAV1 significantly but reduced the percentage of FC and CAV1 in the DRMs. Knockdown of ABCA1 attenuated apoAI-induced redistribution of FC and CAV1. The percentage of FC and CAV1 in the DRMs was correlated inversely with the cellular level of ABCA1, suggesting that apoAI induces relocation of CAV1 and FC from the raft to the non-rail membrane via a mechanism involving upregulation of ABCA1.