期刊
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY
卷 55, 期 1, 页码 49-55出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/FJC.0b013e3181c37d86
关键词
atherosclerosis; macrophages; insulin resistance; ER stress; tauroursodeoxycholic acid
资金
- National Institutes of Health
- National Center for Research Resources [P20RR016474]
- NATIONAL CENTER FOR RESEARCH RESOURCES [P20RR016474] Funding Source: NIH RePORTER
Background/Aim: Recent evidence suggests that endoplasmic reticulum (ER) stress provoked under diabetic conditions augments the expression of scavenger receptors on macrophages, promoting the uptake of oxidized low-density lipoprotein uptake and atherogenesis. The aim of the present study was to test the hypothesis that the chemical chaperone tauroursodeoxycholic acid (TUDCA) attenuates lipid accumulation in macrophages subjected to ER stress. Methods: Cultured human macrophages were subjected to ER stress by treating them with tunicamycin. Lipid uptake by macrophages subjected to ER stress in the presence or absence of TUDCA was assessed by oil red 0 staining and by assessing the cellular uptake of Dil-oxidized low-density lipoprotein by fluorescence measurement. Protein levels and phosphorylation status of ER stress markers, insulin-signaling molecules, and scavenger receptor were assessed by Western blotting. Results: Treatment of cultured human macrophages with the ER stressor tunicamycin caused an increase in the protein levels of cluster of differentiation 36 (CD-36) and augmentation of lipid uptake both of which were inhibited by TUDCA. TUDCA treatment inhibited tunicamycin-induced ER stress as evidenced by the attenuation of phosphorylation of eukaryotic translation initiation factor-2a and glucose reactive protein-78. In addition, TUDCA improved insulin signaling in macrophages by augmenting Akt phosphorylation and blunting c-Jun N-terminal kinase activity. Conclusions: Inhibition of macrophage ER stress may represent a potential strategy in preventing atherogenesis under diabetic conditions.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据