当前位置: 首页 > 详情页

Inhibition of ERK1/2 and Activation of Liver X Receptor Synergistically Induce Macrophage ABCA1 Expression and Cholesterol Efflux

文献详情

资源类型:
WOS体系:

收录情况: ◇ SCIE ◇ 自然指数

机构: [1]College of Life Sciences, Nankai University, Tianjin 300071, China, [2]College of Chemistry, Nankai University, Tianjin 300071, China, [3]Key Lab of Bioactive Materials of the Ministry of Education of China, Nankai University, Tianjin 300071, China, [4]Department of Neurobiology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China, [5]Center of Vascular Biology and Department of Pathology, Weill Medical College of Cornell University, New York, New York 10065
出处:
ISSN:

摘要:
ATP-binding cassette transporter A1 (ABCA1), a molecule mediating free cholesterol efflux from peripheral tissues to apoAI and high density lipoprotein (HDL), inhibits the formation of lipid-laden macrophage/foam cells and the development of atherosclerosis. ERK1/2 are important signaling molecules regulating cellular growth and differentiation. The ERK1/2 signaling pathway is implicated in cardiac development and hypertrophy. However, the role of ERK1/2 in the development of atherosclerosis, particularly in macrophage cholesterol homeostasis, is unknown. In this study, we investigated the effects of ERK1/2 activity on macrophage ABCA1 expression and cholesterol efflux. Compared with a minor effect by inhibition of other kinases, inhibition of ERK1/2 significantly increased macrophage cholesterol efflux to apoAI and HDL. In contrast, activation of ERK1/2 reduced macrophage cholesterol efflux and ABCA1 expression. The increased cholesterol efflux by ERK1/2 inhibitors was associated with the increased ABCA1 levels and the binding of apoAI to cells. The increased ABCA1 by ERK1/2 inhibitors was due to increased ABCA1 mRNA and protein stability. The induction of ABCA1 expression and cholesterol efflux by ERK1/2 inhibitors was concentration-dependent. The mechanism study indicated that activation of liver X receptor (LXR) had little effect on ERK1/2 expression and activation. ERK1/2 inhibitors had no effect on macrophage LXR alpha/beta expression, whereas they did not influence the activation or the inhibition of the ABCA1 promoter by LXR or sterol regulatory element-binding protein (SREBP). However, inhibition of ERK1/2 and activation of LXR synergistically induced macrophage cholesterol efflux and ABCA1 expression. Our data suggest that ERK1/2 activity can play an important role in macrophage cholesterol trafficking.

基金:
语种:
被引次数:
WOS:
PubmedID:
中科院(CAS)分区:
出版当年[2009]版:
大类 | 2 区 生物
小类 | 2 区 生化与分子生物学
最新[2023]版:
大类 | 2 区 生物学
小类 | 2 区 生化与分子生物学
JCR分区:
出版当年[2008]版:
Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
最新[2023]版:
Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

影响因子: 最新[2023版] 最新五年平均 出版当年[2008版] 出版当年五年平均 出版前一年[2007版] 出版后一年[2009版]

第一作者:
第一作者机构: [1]College of Life Sciences, Nankai University, Tianjin 300071, China, [4]Department of Neurobiology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China, [5]Center of Vascular Biology and Department of Pathology, Weill Medical College of Cornell University, New York, New York 10065
通讯作者:
通讯机构: [*]Center of Vascular Biology, Weill Medical College of Cornell University, 1300 York Ave., New York, NY 10065
推荐引用方式(GB/T 7714):
APA:
MLA:

资源点击量:16409 今日访问量:0 总访问量:869 更新日期:2025-01-01 建议使用谷歌、火狐浏览器 常见问题

版权所有©2020 首都医科大学宣武医院 技术支持:重庆聚合科技有限公司 地址:北京市西城区长椿街45号宣武医院