Motohiro Takeya
   Department   Kumamoto Health Science University  Department of Medical Technology, Faculty of Health Science
   Position   Professor
Research Period 2005~2007
Research Topic Identification and characterization of novel vesicular organelle appearing hyperlipidemic human macrophages
Research Type KAKENHI Research
Consignor Ministry of Education, Culture, Sports, Science and Technology
Research Program Type Grants-in-Aid for Scientific Research(基盤研究(B)),基盤研究(B)
KAKENHI Grant No. 17390115
Representative Person Naomi SAKASHITA
Collaborative Researcher Motohiro TAKEYA
Details The macrophages under hyperlipidemic condition continuously internalize modified low density lipoprotein (LDL) and transformed to lipid laden (foamy transformed) macrophages in the arterial wall. These lipid-laden macrophages promote atherosclerosis via producing various chemokines and cytokines, therefore, mechanism of foamy transformation of the macrophages is key issue to investigate atherogenesis. Internalized modified LDL is hydrolyzed in the LAMP2-positive hydrolytic compartment, free cholesterol derived from modified LDL is transferred to the endoplasmic reticulum (ER), ACAT1, an ER resident enzyme, esterifies cholesterol, esterified cholesterol is stored as lipid droplets, thus macrophages turn into lipid laden macrophages. We discovered foamy transformed macrophages produce ER-derived, ACAT1-positive vesicular organelle (Am J Pathol, 156:227-236, 2000). To investigate the nature of these vesicles, we analyzed lipid-laden human macrophages by means of subcellular fractionation assay. Most of ACAT1 appeared in middle density fractions that have negligible ACAT enzymatic activity in cholesterol poor situation, while it moved to low density fractions with significant ACAT acti
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