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Papers In Press, published online ahead of print June 1, 2005
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Biochemistry, Cell Biology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi 467-8601
Corresponding Author: syokoyam{at}med.nagoya-cu.ac.jp
Assembly of high density lipoprotein (HDL) by helical apolipoprotein and cellular lipid was studied by using the HEK293 cells to which ecdysone-inducible human ATP-binding cassette transporter (ABC) A1 or human ABCA7 was transfected. Expression of ABCA1 and ABCA7 were both induced linearly proportional to ponasterone A concentration in the medium. In the experimental condition employed, the ABCA protein expression levels limit the rate of lipid release when the apolipoprotein concentration is high and the apolipoprotein concentration is rate-limiting when the ABC protein expression levels are high. As ABCA1 expression increased in the conditions that it was rate-limiting, relative cholesterol content to phospholpid 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 mostly generated small cholesterol-poor particles. The increase of HDL assembly with the increase of ABCA1 expression was predominant in large cholesterol-rich particles, while only small cholesterol-poor HDL increased as ABCA7 expression increased. We concluded that ABCA1 generates cholesterol-rich and cholesterol-poor HDL and the former is more prominently dependent on the increase of ABCA1 expression. ABCA7 produces this HDL subfraction only as a very minor component.
Revised on April 25, 2005
Accepted on May 24, 2005
Heterogeneity of high density lipoprotein generated by ABCA1 and ABCA7
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