Nascent HDL formation in hepatocytes and role of ABCA1, ABCG1, and SR-BI

作者：Ji Ailing; Wroblewski Joanne M; Cai Lei; de Beer Maria C; Webb Nancy R; van der Westhuyzen Deneys R^*

来源：The Journal of Lipid Research, 2012, 53(3): 446-455.

DOI：10.1194/jlr.M017079

• ATP binding cassette transporter A1
• ATP binding cassette transporter G1
• class B scavenger receptor type 1
• high density lipoprotein formation
• cholesterol efflux
• hepatocyte

To study the mechanisms of hepatic HDL formation, we investigated the roles of ABCA1, ABCG1, and SR-BI in nascent HDL formation in primary hepatocytes isolated from mice deficient in ABCA1, ABCG1, or SR-BI and from wild-type (WT) mice. Under basal conditions, in WT hepatocytes, cholesterol efflux to exogenous apoA-I was accompanied by conversion of apoA-I to HDL-sized particles. LXR activation by T0901317 markedly enhanced the formation of larger HDL-sized particles as well as cellular cholesterol efflux to apoA-I. Glyburide treatment completely abolished the formation of 7.4 nm diameter and greater particles but led to the formation of novel 7.2 nm-sized particles. However, cells lacking ABCA1 failed to form such particles. ABCG1-deficient cells showed similar capacity to efflux cholesterol to apoA-I and to form nascent HDL particles compared with WT cells. Cholesterol efflux to apoA-I and nascent HDL formation were slightly but significantly enhanced in SR-BI-deficient cells compared with WT cells under basal but not LXR activated conditions. As in WT but not in ABCA1-deficient hepatocytes, 7.2 nm-sized particles generated by glyburide treatment were also detected in ABCG1-deficient and SR-BI-deficient hepatocytes. Our data indicate that hepatic nascent HDL formation is highly dependent on ABCA1 but not on ABCG1 or SR-BI.-Ji, A., J. M. Wroblewski, L. Cai, M. C. de Beer, N. R. Webb, and D. R. van der Westhuyzen. Nascent HDL formation in hepatocytes and role of ABCA1, ABCG1, and SR-BI. J. Lipid Res. 2012. 53: 446-455.

• 出版日期2012-3