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J. Lipid Res.
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Originally published In Press as doi:10.1194/jlr.M400222-JLR200 on September 17, 2004 Originally published In Press as doi:10.1194/jlr.M400222-JLR200 on September 16, 2004

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Journal of Lipid Research, Vol. 45, 2269-2276, December 2004
Copyright © 2004 by American Society for Biochemistry and Molecular Biology

Apolipoprotein A-I induces translocation of protein kinase C{alpha} to a cytosolic lipid-protein particle in astrocytes

Jin-ichi Ito, Hao Li1, Yuko Nagayasu, Alireza Kheirollah and Shinji Yokoyama2

Biochemistry, Cell Biology, and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan

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

Apolipoprotein A-I (apoA-I) induces the translocation of newly synthesized cholesterol as well as caveolin-1 to the cytosolic lipid-protein particle (CLPP) fraction in astrocytes before its appearance in high density lipoprotein generated in the medium (Ito, J., Y. Nagayasu, K. Kato, R. Sato, and S. Yokoyama. 2002. Apolipoprotein A-I induces translocation of cholesterol, phospholipid, and caveolin-1 to cytosol in rat astrocytes. J. Biol. Chem. 277: 7929–7935). We here report the association of signal-related molecules with CLPP. ApoA-I induces rapid translocation of protein kinase C{alpha} to the CLPP fraction and its phosphorylation in astrocytes. ApoA-I also induces the translocation of phospholipase C{gamma} to CLPP. Diacylglyceride (DG) production is increased by apoA-I in the cells, with a maximum at 5 min after the stimulation, and the increase takes place also in the CLPP fraction. An inhibitor of receptor-coupled phospholipase C, U73122, inhibited all the apoA-I-induced events, such as DG production, cholesterol translocation to the cytosol, release of cholesterol, and translocation of protein kinase C{alpha} into the CLPP fraction.

CLPP may thus be involved in the apoA-I-initiated signal transduction in astrocytes that is related to intracellular cholesterol trafficking for the generation of high density lipoprotein in the brain.

Abbreviations: apoA-I, apolipoprotein A-I; apoE-KO mouse, apoE knockout C57BL/6 mouse; CLPP, cytosolic lipid-protein particle; CSF, cerebrospinal fluid; DG, diacylglyceride; DPBS, Dulbecco's phosphate-buffered saline; FCS, fetal calf serum; PI, phosphatidylinositol

Supplementary key words caveolin-1 • phospholipase C • phosphatidylinositol turnover • cholesterol


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