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著作: Lei XiaoFeng/Fujiwara Yukio/Chang C. Y. Catherine/Chang Ta-Yuan/Takeya Motohiro/[坂下 直実]/Association of ACAT1-positive vesicles with late endosomes/ lysosomes in cholesterol-rich human macrophages./[Journal of Atherosclerosis and Thrombosis]

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EID
269150
EOID
819652
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LastModified
2016年5月11日(水) 11:12:36
Operator
大家 隆弘
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坂下 直実
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種別 必須
言語 必須 英語
招待 推奨
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共著種別 推奨
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組織 推奨
著者 必須
  1. (英) Lei XiaoFeng
    役割 任意
    貢献度 任意
    学籍番号 推奨
  2. (英) Fujiwara Yukio
    役割 任意
    貢献度 任意
    学籍番号 推奨
  3. (英) Chang C. Y. Catherine
    役割 任意
    貢献度 任意
    学籍番号 推奨
  4. (英) Chang Ta-Yuan
    役割 任意
    貢献度 任意
    学籍番号 推奨
  5. (英) Takeya Motohiro
    役割 任意
    貢献度 任意
    学籍番号 推奨
  6. 坂下 直実
    役割 任意
    貢献度 任意
    学籍番号 推奨
題名 必須

(英) Association of ACAT1-positive vesicles with late endosomes/ lysosomes in cholesterol-rich human macrophages.

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要約 任意

(英) Acyl-coenzyme A: cholesterol acyltransferase1 (ACAT1) is an endoplasmic reticulum (ER)-resident enzyme that catalyzes the conversion of cholesterol into cholesteryl esters. We previously showed that cholesterol-loaded macrophages produce numerous ER-derived vesicles with elevated ACAT1 enzyme activity; some of these vesicles were shown to be closely associated with Golgi-related organelle(s). The aim of this study was to investigate the translocation of ACAT1 vesicle in cholesterol-loaded macrophages. To demonstrate association of ACAT1 with late endosomes/lysosomes (LE/LS), primary human macrophages with or without cholesterol-loading was subjected to confocal microscopy, immunoelectron microscopy, subcellular fractionation, and immunoadsorption assay. Furthermore, cholesterol esterification assay was also carried out to investigate function of ACAT1 associated LE/LS. Confocal fluorescence microscopy revealed that no significant ACAT1 signal was associated with the signal for LAMP2, a marker protein for LE/LS, in cholesterol non-loaded macrophages; however, approximately 20% of the total ACAT1 signals colocalized with the LAMP2 signal in cholesterol-loaded macrophages. ACAT1-positive membranes isolated by immunoadsorption using ACAT1-specific antibody contained LAMP2, demonstrating the association of ACAT1 and LE/LS. In addition, in macrophages phagocytosing latex beads, the close association of ACAT1 with LE/LS can be demonstrated in phagosomes isolated from cholesterol-loaded macrophages, not from non-loaded macrophages. Furthermore, cholesterol-loaded macrophages re-esterified aggregated LDL-derived cholesteryl ester even in the presence of U18666A, a reagent known to block egression of cholesterol from LE/LS. Our results indicated that cholesterol-loaded human macrophages produce LE/LS in close association with ACAT1, and may promote efficient esterification of modified LDL-derived free cholesterol on LE/LS.

キーワード 推奨
  1. (英) Acetyl-CoA C-Acetyltransferase
  2. (英) Animals
  3. (英) Cells, Cultured
  4. (英) Cholesterol
  5. (英) Endoplasmic Reticulum
  6. (英) Endosomes
  7. (英) Esterification
  8. (英) Humans
  9. (英) Immunoblotting
  10. (英) Lysosomal-Associated Membrane Protein 2
  11. (英) Lysosomes
  12. (英) Macrophages
  13. (英) Mice
  14. (英) Subcellular Fractions
発行所 推奨
誌名 必須 Journal of Atherosclerosis and Thrombosis(日本動脈硬化学会)
(pISSN: 1340-3478, eISSN: 1880-3873)
ISSN 任意 1880-3873
ISSN: 1340-3478 (pISSN: 1340-3478, eISSN: 1880-3873)
Title: Journal of atherosclerosis and thrombosis
Title(ISO): J Atheroscler Thromb
Supplier: 一般社団法人 日本動脈硬化学会
Publisher: Japan Atherosclerosis Society
 (NLM Catalog  (医中誌Web  (J-STAGE  (Scopus  (CrossRef (Scopus information is found. [need login])
必須 17
必須 7
必須 740 750
都市 任意
年月日 必須 2010年 6月 2日
URL 任意
DOI 任意 10.5551/jat.4416    (→Scopusで検索)
PMID 任意 20523008    (→Scopusで検索)
NAID 任意
WOS 任意 000282824200009
Scopus 任意
評価値 任意
被引用数 任意
指導教員 推奨
備考 任意
  1. (英) Article.Affiliation: Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, Japan.

  2. (英) Article.PublicationTypeList.PublicationType: Journal Article

  3. (英) Article.PublicationTypeList.PublicationType: Research Support, Non-U.S. Gov't