Effects of NTE-122, a Novel Acyl-CoA:Cholesterol Acyltransferase Inhibitor, on Cholesterol Esterification and High-Density Lipoprotein-Induced Cholesterol Efflux in Macrophages.

DOI Web Site Web Site Web Site Web Site ほか1件をすべて表示 一部だけ表示 被引用文献2件 参考文献48件

この論文をさがす

抄録

We investigated the effects of a novel acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor, NTE-122 (trans-1, 4-bis[[1-cyclohexyl-3-(4-dimethylamino phenyl)ureido]methyl]cyclohexane), on ACAT activities in macrophages originating from several species and high-density lipoprotein (HDL)-induced cholesterol efflux in phorbol 12-myristate 13-acetate (PMA)-treated THP-1 cells. NTE-122 inhibited cell-free ACAT activities in human PMA-treated THP-1 cells and mouse J774.1 cells with IC50 values of 0.88 and 360 nM, respectively. NTE-122 competively inhibited the ACAT activity in PMA-treated THP-1 cells. NTE-122 also inhibited cellular ACAT activities in PMA-treated THP-1 cells, rat peritoneal macrophages and J774.1 cells with IC50 values of 3.5, 84 and 6800 nM, respectively. Furthermore, NTE-122 prevented cholesterol accumulation in PMA-treated THP-1 cells incubated with acetylated low density lipoprotein, simultaneously with HDL, while it caused accumulation of a significant amount of free cholesterol in the absence and even in the presence of HDL. NTE-122 also enhanced HDL-induced cholesterol efflux from established foam cells converted from PMA-treated THP-1 cells. These results suggest that NTE-122, capable of inhibiting macrophage ACAT activity in humans more strongly than those in the other species, exhibits anti-atherogenic effects by preventing the foam cell formation and enhancing the foam cell regression in humans.

収録刊行物

  • Jpn.J.Pharmacol.

    Jpn.J.Pharmacol. 79 (2), 159-167, 1999

    公益社団法人 日本薬理学会

被引用文献 (2)*注記

もっと見る

参考文献 (48)*注記

もっと見る

キーワード

詳細情報 詳細情報について

問題の指摘

ページトップへ