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| Content Provider | Journal of Biological Chemistry (JBC) |
|---|---|
| Author | Reddy, Srinivasa Hama, Susan Grijalva, Victor Hassan, Khaled Mottahedeh, Rachel Hough, Greg Wadleigh, David J. Navab, Mohamad Fogelman, Alan M. |
| Abstract | Entrapment and oxidation of low density lipoproteins (LDL) in the sub-endothelial space is a key process in the initiation of atherosclerotic lesion development. Functional changes induced by oxidized lipids in endothelial cells are early events in the pathogenesis of atherosclerosis. Oxidized-l-α-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (ox-PAPC), a major component of minimally modified/oxidized-LDL (MM-LDL) mimics the biological activities assigned to MM-LDL bothin vitro in a co-culture model as well as in vivo in mice. We hypothesized that ox-PAPC initiates gene expression changes in endothelial cells that result in enhanced endothelial/monocyte interactions. To analyze the gene expression changes that oxidized lipids induce in endothelial cells, we used a suppression subtractive hybridization procedure to compare mRNA from PAPC-treated human aortic endothelial cells (HAEC) with that of ox-PAPC-treated cells. We report here the identification of a gene, mitogen-activated protein kinase phosphatase 1 (MKP-1), that is rapidly and transiently induced in ox-PAPC-treated HAEC. Inhibition of MKP-1 using either the phosphatase inhibitor sodium orthovanadate or antisense oligonucleotides prevents the accumulation of monocyte chemotactic activity in ox-PAPC-treated HAEC supernatants. Furthermore, we show that decreased monocyte chemotactic activity in HAEC treated with sodium orthovanadate or MKP-1 antisense oligonucleotides is due to decreased MCP-1 protein. Our results implicate a direct role for MKP-1 in ox-PAPC-induced signaling pathways that result in the production of MCP-1 protein by ox-PAPC-treated HAEC. |
| Related Links | http://www.jbc.org/content/276/20/17030.abstract |
| Ending Page | 17035 |
| Starting Page | 17030 |
| Page Count | 6 |
| File Format | HTM / HTML PDF |
| ISSN | 00219258 |
| Journal | Journal of Biological Chemistry (JBC) |
| Issue Number | 20 |
| Volume Number | 276 |
| DOI | 10.1074/jbc.M011663200 |
| e-ISSN | 1083351X |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology |
| Publisher Date | 2001-05-18 |
| Access Restriction | Open |
| Subject Keyword | Low density lipoprotein (LDL) Mildly oxidized-LDL (MM-LDL) Mitogen-activated protein kinase (MAPK) MAPK phosphatase 1 (MKP-1) Monocyte chemoattractant protein 1 (MCP-1) Interleukin 8 (IL-8) Apolipoprotein (apo) 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (PAPC) Oxidized-PAPC (ox-PAPC) 1-palmitoyl-2 (5-oxovaleroyl)-sn-glycero-3-phosphocholine (POVPC) 1palmitoyl-2-glutaroyl-sn-glycero-3-phosphocholine (PGPC) 1-palmitoyl-2 (5, 6-epoxyisoprostane E2)-sn-glycero-3-phosphocholine (PEIPC) Human aortic endothelial cells (HAEC) High performance liquid chromatography (HPLC) Enzyme-linked immunosorbent assay (ELISA) LIPIDS AND LIPOPROTEINS |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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