アクセス数 : ?
ダウンロード数 : ?
ID 109570
著者
坂下, 直実 Department of Human Pathology, Institute of Health Biosciences, the University of Tokushima Graduate School KAKEN研究者をさがす
Lei, XiaoFeng Department of Biochemistry, Showa University
カミカワ, マサシ Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University
ニシツジ, カズチカ Department of Human Pathology, Institute of Health Biosciences, the University of Tokushima Graduate School KAKEN研究者をさがす
キーワード
ACAT1
late endosomes
macrophages
cholesterol metabolism
Niemann-Pick disease type C
資料タイプ
学術雑誌論文
抄録
Macrophages in hyperlipidemic conditions accumulate cholesterol esters and develop into foamy transformed macrophages. During this transformation, macrophages demonstrate endoplasmic reticulum fragmentation and consequently produce acyl coenzyme A : cholesterol acyltransferase 1 (ACAT1-positive late endosomes (ACAT1-LE). ACAT1-LE-positive macrophages effectively esterify modified or native low-density lipoprotein-derived free cholesterol, which results in efficient cholesterol esterification as well as atherosclerotic plaque formation. These macrophages show significant cholesterol ester formation even when free cholesterol egress from late endosomes is impaired, which indicates that free cholesterol is esterified at ACAT1-LE. Genetic blockade of cholesterol egress from late endosomes causes Niemann-Pick disease type C (NPC), an inherited lysosomal storage disease with progressive neurodegeneration. Induction of ACAT1-LE in macrophages with the NPC phenotype led to significant recovery of cholesterol esterification. In addition, in vivo ACAT1-LE induction significantly extended the lifespan of mice with the NPC phenotype. Thus, ACAT1-LE not only regulates intracellular cholesterol metabolism but also ameliorates NPC pathophysiology.
掲載誌名
The journal of medical investigation : JMI
ISSN
13431420
cat書誌ID
AA11166929
61
3-4
開始ページ
270
終了ページ
277
並び順
270
発行日
2014-08
EDB ID
フルテキストファイル
言語
eng
著者版フラグ
出版社版
部局
医学系