ABCA1 modulates the oligomerization and Golgi exit of caveolin-1 during HDL-mediated cholesterol efflux in aortic endothelial cells.
Previously, the authors have shown that the molecular interaction between caveolin-1 and ATP-binding cassette transporter A1 (ABCA1) is associated with the high-density lipoprotein (HDL)-mediated cholesterol efflux pathway in aortic endothelial cells (ECs). This study analyzed the role ABCA1 plays in caveolin-1-mediated cholesterol efflux in aortic ECs. Knockdown of ABCA1 by siRNA in primary rat aortic ECs after cholesterol treatment did not affect caveolin-1 expression but led to the retention of caveolin-1 in the Golgi apparatus, impaired caveolin-1 oligomerization, and reduced cholesterol efflux. Immunoblotting assay and immunofluorescence microscopy demonstrated that HDL transiently up-regulated ABCA1 expression, induced caveolin-1 oligomerization, and promoted its Golgi exit, thereby enhancing cholesterol efflux. These HDL-induced events, however, were inhibited by down-regulation of ABCA1. It is concluded that HDL up-regulates ABCA1 expression, which in turn modulates the oligomerization and Golgi exit of caveolin-1 to enhance cholesterol efflux in aortic ECs.
Lin
Yu-Chun
YC
Department of Life Science, Tunghai University, 181 Taichung Harbor Road, Section 3, Taichung 40704, Taiwan, ROC.
Lin
Chun-Huan
CH
Kuo
Chan-Yen
CY
Yang
Vivian C
VC
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051242:Caveolin 1 / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D015536:Down-Regulation; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D006056:Golgi Apparatus / Q000378:metabolism*; D008075:Lipoproteins, HDL / Q000378:metabolism* / Q000494:pharmacology; D021381:Protein Transport; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D051242:Caveolin 1; D008075:Lipoproteins, HDL; D034741:RNA, Small Interfering; D002784:Cholesterol