| 論文名 |
Bis(monoacylglycero)phosphate accumulation in macrophages induces intracellular cholesterol redistribution, attenuates liver-X receptor/ATP-Binding cassette transporter A1/ATP-binding cassette transporter G1 pathway, and impairs cholesterol efflux. |
| 著者 |
C?line Luquain-Costaz
Etienne Lefai
Maud Arnal-Levron
Daria Markina
Shota Saka?
Vanessa Euthine
Asami Makino
Michel Guichardant
Shizuya Yamashita
Toshihide Kobayashi
Michel Lagarde
Philippe Moulin
Isabelle Delton-Vandenbroucke
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| キーワード |
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| 出版年月 |
1970年1月 |
| 発表先 |
Arterioscler Thromb Vasc Biol. 2013 Aug;33(8):1803-11. |
| WEBサイト |
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| 論文概要（和文） |
マクロファージにおけるビス（モノアシルグリセロ）リン酸の蓄積は、細胞内コレステロール再分布を誘発し、肝臓X受容体/ ATP結合カセットトランスポーターA1 / ATP結合カセットトランスポーターG1経路を減衰させ、コレステロール流出を損なう。 |
| 論文概要（英文） |
Objective: Endosomal signature phospholipid bis(monoacylglycero)phosphate (BMP) has been involved in the regulation of cellular cholesterol homeostasis. Accumulation of BMP is a hallmark of lipid storage disorders and was recently reported as a noticeable feature of oxidized low-density lipoprotein-laden macrophages. This study was designed to delineate the consequences of macrophage BMP accumulation on intracellular cholesterol distribution, metabolism, and efflux and to unravel the underlying molecular mechanisms. Approach and results: We have developed an experimental design to specifically increase BMP content in RAW 264.7 macrophages. After BMP accumulation, cell cholesterol distribution was markedly altered, despite no change in low-density lipoprotein uptake and hydrolysis, cholesterol esterification, or total cell cholesterol content. The expression of cholesterol-regulated genes sterol regulatory element-binding protein 2 and hydroxymethylglutaryl-coenzyme A reductase was decreased by 40%, indicative of an increase of endoplasmic reticulum-associated cholesterol. Cholesterol delivery to plasma membrane was reduced as evidenced by the 20% decrease of efflux by cyclodextrin. Functionally, BMP accumulation reduced cholesterol efflux to both apolipoprotein A1 and high-density lipoprotein by 40% and correlated with a 40% decrease in mRNA contents of ATP-binding cassette transporter A1, ATP-binding cassette transporter G1, and liver-X receptor α and β. Foam cell formation induced by oxidized low-density lipoprotein exposure was exacerbated in BMP-enriched cells. Conclusions: The present work shows for the first time a strong functional link between BMP and cholesterol-regulating genes involved in both intracellular metabolism and efflux. We propose that accumulation of cellular BMP might contribute to the deregulation of cholesterol homeostasis in atheromatous macrophages. |
