Abstract | AIMS: METHODS: Human THP-1 monocytes were preincubated with Phorbol-12-myristate- 13-acetate (PMA) and oxidized low density lipoprotein ( ox-LDL) to form foam cells. The protein and mRNA expression were examined by western immunoblotting assays and real-time quantitative PCR, respectively. Cellular cholesterol content was measured by HPLC. The cholesterol efflux was assessed by liquid scintillation counting. RESULTS:
AOPPs significantly decreased the expression of ATP-binding membrane cassette transporter A-1 (ABCA1) and liver X receptor α (LXRα) and reduced cholesterol efflux from THP-1 macrophage- derived foam cells. AOPPs substantially activated NADPH oxidase and activated Janus kinase/signal transducers and activators of transcription (JAK/STAT) signal pathway in THP-1-derived foam-like cells. Inhibiting NADPH oxidase by diphenyliodonium (DPI) effectively abolished the AOPPs-induced decrease in cholesterol efflux and the expression of ABCA1. Inhibiting JAK/STAT activation by its specific inhibitor AG-490 or by siRNA could also block AOPPs action on THP-1 cells. CONCLUSIONS:
AOPPs may first down-regulate the expression of LXRα and ABCA1 through JAK/STAT signal pathway activation and then inhibit cholesterol efflux in THP-1-derived foam-like cells; therefore, our study may be useful for understanding the critical effects of AOPPs on the pathogenesis of atherosclerosis.
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Authors | Zhong-Cheng Mo, Ji Xiao, Xie-Hong Liu, Yan-Wei Hu, Xiao-Xu Li, Guang-Hui Yi, Zuo Wang, Ya-Ling Tang, Duan-Fang Liao, Chao-Ke Tang |
Journal | Journal of atherosclerosis and thrombosis
(J Atheroscler Thromb)
Vol. 18
Issue 9
Pg. 796-807
( 2011)
ISSN: 1880-3873 [Electronic] Japan |
PMID | 21670559
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- ABCA1 protein, human
- ATP Binding Cassette Transporter 1
- ATP-Binding Cassette Transporters
- Proteins
- STAT Transcription Factors
- Cholesterol
- Janus Kinases
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Topics |
- ATP Binding Cassette Transporter 1
- ATP-Binding Cassette Transporters
(metabolism)
- Cell Line
- Cholesterol
(metabolism)
- Down-Regulation
- Humans
- Janus Kinases
(metabolism)
- Proteins
(metabolism)
- STAT Transcription Factors
(metabolism)
- Signal Transduction
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