Motohiro Takeya
   Department   Kumamoto Health Science University  Department of Medical Technology, Faculty of Health Science
   Position   Professor
Research Period 2004~2005
Research Topic Elucidation of the mechanisms for intracellular accumulation of cholesterol ester and its application to therapies.
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(C)),基盤研究(C)
KAKENHI Grant No. 16590895
Representative Person Akira MIYAZAKI
Collaborative Researcher Shigeki HONGO, Motohiro TAKEYA, Takuya WATANABE
Details Acyl-coenzyme A : cholesterol acyltransferase-1 (ACAT-1) converts intracellular free cholesterol into cholesterol ester for storage in lipid droplets and plays an important role in the formation of macrophage-derived foam cells in atherosclerotic lesions. Serotonin (5-HT), a potentvasoconstrictor that is released from activated platelets, increases uptake of oxidized low-density lipoprotein (LDL) by macrophages, leading to foam cell formation, and contributes to the development of atherosclerotic plaque. However, it is not yet known whether 5-HT affects ACAT-1 expression in human monocyte-macrophages as the molecular mechanism of 5-HT-induced foam cell formation. We examined the effects of 5-HT on ACAT-1 expression during differentiation of cultured human monocytes into macrophages. Expression of ACAT-1 protein but not 5-HT_<2A>receptor increased in a time-dependent manner. 5-HT increased ACAT activity in a concentration-dependent manner after seven days in primary monocyte culture. Immunoblotting analysis showed that 5-HT at 10μM increased ACAT-1 protein expression level by two-fold, and this effect was abolished completely by a 5-HT_<2A>receptor antagonist (sarpogrelate), Nor
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