Cholesterol efflux to apolipoprotein AI involves endocytosis and resecretion in a calcium-dependent pathway

Proceedings of the National Academy of Sciences of the United States of America - Tập 96 Số 20 - Trang 11358-11363 - 1999
Yukihiro Takahashi1, Jonathan D. Smith2
1The Rockefeller University, 1230 York Avenue, New York, NY 10021 USA#TAB#
2The Rockefeller University, 1230 York Avenue, New York, NY 10021

Tóm tắt

We previously have described the cAMP-mediated induction of cholesterol and phospholipid efflux from the murine macrophage RAW264 cell line to lipid-free apolipoprotein acceptors. This induction of cholesterol efflux is associated with increased binding and association of apolipoprotein to the cells. In the present study, using primarily apolipoprotein AI (apoAI) as the acceptor, cAMP-dependent cholesterol efflux to apolipoprotein acceptors was associated with apoAI binding to coated pits, cellular uptake, and resecretion. After cell association and washing, 58% of the apoAI was resecreted during a 90-min chase period. In addition, after apoAI uptake and washing, cholesterol efflux was observed during a chase period without additional acceptors. Cholesterol efflux was partially blocked by chlorpromazine and hypertonic media, two inhibitors of coated pit endocytosis. Cholesterol efflux to apoAI was found to depend on extracellular calcium. By temporally separating the cAMP induction phase from the apoAI chase phase, calcium was found to be required during the apoAI chase phase rather than during the cAMP induction period. In the absence of calcium the 8-Br-cAMP-mediated induction of apoAI binding was maintained, but the specific apoAI cellular association was inhibited. The data are consistent with a model for cholesterol efflux to apolipoproteins that involves a calcium-dependent endocytic pathway, followed by recycling and the subsequent release of the nascent lipoprotein particle from the cell.

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Proceedings of the National Academy of Sciences of the United States of America

Tập 96 Số 20

11358-11363

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