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Journal of Lipid Research, Vol. 46, 1703-1711, August 2005
Copyright © 2005 by American Society for Biochemistry and Molecular Biology

Heterogeneity of high density lipoprotein generated by ABCA1 and ABCA7

Michi Hayashi^*, Sumiko Abe-Dohmae^*, Mitsuyo Okazaki, Kazumitsu Ueda and Shinji Yokoyama^1,*

^* Biochemistry, Cell Biology, and Metabolism, Nagoya City University Graduate School of Medical Sciences, Kawasumi 1, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan
Laboratory of Chemistry, College of Liberal Arts and Science, Tokyo Medical and Dental University, Ichikawa 272-0827, Japan
Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Kitashirakawa, Sakyo-ku, Kyoto 606-8502, Japan

Published, JLR Papers in Press, June 1, 2005. DOI 10.1194/jlr.M500092-JLR200

¹ To whom correspondence should be addressed. e-mail: syokoyam{at}med.nagoya-cu.ac.jp

The assembly of HDL by helical apolipoprotein and cellular lipid was studied using HEK293 cells to which ecdysone-inducible human ABCA1 or human ABCA7 was transfected. Expression of both ABCA1 and ABCA7 was induced linearly proportional to ponasterone A concentration in the medium. In the experimental conditions used, the ABC protein expression levels limited the rate of lipid release when the apolipoprotein concentration was high, and the apolipoprotein concentration was rate-limiting when the ABC protein expression levels were high. When ABCA1 expression increased in conditions in which it was rate-limiting, relative cholesterol content to phospholipid increased in the HDL produced. In contrast, it was constant when ABCA7 expression increased. To investigate the background mechanism, the HDL particles were analyzed by density gradient ultracentrifugation and high performance lipid chromatography. The ABCA1-mediated reaction produced two distinct HDLs, large cholesterol-rich and small cholesterol-poor particles, and the ABCA7-mediated reaction generated mostly small cholesterol-poor particles. The increase of HDL assembly with the increase of ABCA1 expression was predominant in large cholesterol-rich particles, whereas only small cholesterol-poor HDL increased as ABCA7 expression increased.

We conclude that ABCA1 generates cholesterol-rich and cholesterol-poor HDL and that the former is more prominently dependent on the increase of ABCA1 expression. ABCA7 produces this HDL subfraction only as a very minor component.

Abbreviations: apoA-I, apolipoprotein A-I; DF, 1:1 mixture of Dulbecco's modified Eagle's medium and Ham's F-12 medium; GFP, green fluorescent protein

Supplementary key words ATP binding cassette transporter A1 • ATP binding cassette transporter A7 • cholesterol • ecdysone-inducible

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