OxLDL stimulates lipoprotein-associated phospholipase A(2) expression in THP-1 monocytes via PI3K and p38 MAPK pathways
文献类型：期刊论文
| 作者 | Wang, Wen-Yi1,2; Li, Jie2; Yang, Ding2; Xu, Wei1,2; Zha, Ruo-peng1,2; Wang, Yi-ping2
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| 刊名 | CARDIOVASCULAR RESEARCH
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| 出版日期 | 2010-03-01 |
| 卷号 | 85期号:4页码:845-852 |
| 关键词 | Atherosclerosis lp-PLA2 oxLDL p38 PI3K |
| ISSN号 | 0008-6363 |
| DOI | 10.1093/cvr/cvp367 |
| 文献子类 | Article |
| 英文摘要 | Lipoprotein-associated phospholipase A(2) (lp-PLA(2)) has been detected in human and rabbit atherosclerotic lesions, where it co-localizes with its substrate, oxidized LDL (oxLDL). Here, we investigated whether oxLDL may exert a regulatory effect on lp-PLA(2) expression. Using human monocytic THP-1 cells as a model system, we found that oxLDL up-regulated the expression of lp-PLA(2) while another substrate of the enzyme, platelet activating factor, had no such effect. The up-regulatory effect of oxLDL could be conferred by its oxidized phospholipids (oxPCs, the exact substrates of lp-PLA(2)), but not their hydrolyzed products, lysophosphatidylcholines (lysoPCs). OxLDL induced the activation of p38 mitogen-activating protein kinase (MAPK) through phosphatidylinositol 3-kinase (PI3K). Inhibition of either PI3K or p38 MAPK completely blocked oxLDL-induced lp-PLA(2) expression. In addition, inhibition of lp-PLA(2) activity in the conditioned medium significantly decreased lipid accumulation in macrophages as detected by oil red staining. The present study shows that oxLDL, and more specifically its unhydrolyzed oxidized phospholipids, can up-regulate lp-PLA(2) expression in monocytes through the PI3K and p38 MAPK pathway. In turn, lp-PLA(2) promotes lipoprotein uptake in macrophages. Our results uncover a new link between oxLDL and lp-PLA(2), and may provide insight into this interaction in the context of atherosclerosis. |
| WOS关键词 | ACTIVATING-FACTOR-ACETYLHYDROLASE ; LOW-DENSITY-LIPOPROTEIN ; CORONARY-HEART-DISEASE ; PROTEIN-KINASE CASCADES ; OXIDIZED PHOSPHOLIPIDS ; ATHEROSCLEROTIC PLAQUE ; OXIDATION-PRODUCTS ; ARTERY-DISEASE ; RISK-FACTORS ; INFLAMMATION |
| 资助项目 | National Basic Research Program of China[2009CB930300] |
| WOS研究方向 | Cardiovascular System & Cardiology |
| 语种 | 英语 |
| WOS记录号 | WOS:000274487900024 |
| 出版者 | OXFORD UNIV PRESS |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/278959]  |
| 专题 | 药理学第一研究室 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
| 通讯作者 | Wang, Yi-ping |
| 作者单位 | 1.Chinese Acad Sci, Grad Sch, Beijing, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Wang, Wen-Yi,Li, Jie,Yang, Ding,et al. OxLDL stimulates lipoprotein-associated phospholipase A(2) expression in THP-1 monocytes via PI3K and p38 MAPK pathways[J]. CARDIOVASCULAR RESEARCH,2010,85(4):845-852. |
| APA | Wang, Wen-Yi,Li, Jie,Yang, Ding,Xu, Wei,Zha, Ruo-peng,&Wang, Yi-ping.(2010).OxLDL stimulates lipoprotein-associated phospholipase A(2) expression in THP-1 monocytes via PI3K and p38 MAPK pathways.CARDIOVASCULAR RESEARCH,85(4),845-852. |
| MLA | Wang, Wen-Yi,et al."OxLDL stimulates lipoprotein-associated phospholipase A(2) expression in THP-1 monocytes via PI3K and p38 MAPK pathways".CARDIOVASCULAR RESEARCH 85.4(2010):845-852. |
入库方式： OAI收割
来源：上海药物研究所
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