Abstract |
Oxidized LDL ( oxLDL) promotes lipid accumulation as well as growth and survival signaling in macrophages. OxLDL uptake is mainly due to scavenger receptors SR-AI/II and CD36. However, other scavenger receptors such as lectin-like oxLDL receptor-1 (LOX-1) may also play a role. We used mice with targeted inactivation of the LOX-1 gene to define the role of this receptor in the uptake of oxLDL and in activation of survival pathways. There was no difference in uptake or degradation of 125I-oxLDL in unstimulated macrophages from wild-type and LOX-1 knockout mice and no difference in the rate of clearance of oxLDL from plasma in vivo. However, when expression of LOX-1 was induced with lysophosphatidylcholine, oxLDL uptake and degradation increased 2-fold in wild-type macrophages but did not change in LOX-1 knockout macrophages. Macrophages lacking LOX-1 showed the same stimulation of PKB phosphorylation and enhancement of survival by oxLDL as wild-type cells. These data show that LOX-1 does not alter the uptake of oxLDL in unstimulated macrophages and is not essential for the pro-survival effect of oxLDL in these cells. However, LOX-1 expression is highly inducible by lysophosphatidylcholine and pro-inflammatory cytokines, and if that occurred in macrophages within atheromas, LOX-1 could substantially increase oxLDL uptake by lesion macrophages.
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Authors | David F Schaeffer, Maziar Riazy, Kuljit S Parhar, Johnny H Chen, Vincent Duronio, Tatsuya Sawamura, Urs P Steinbrecher |
Journal | Journal of lipid research
(J Lipid Res)
Vol. 50
Issue 8
Pg. 1676-84
(Aug 2009)
ISSN: 1539-7262 [Electronic] United States |
PMID | 19359704
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Lipoproteins, LDL
- Lysophosphatidylcholines
- Olr1 protein, mouse
- RNA, Messenger
- Scavenger Receptors, Class E
- oxidized low density lipoprotein
- stearoyl alpha-lysolecithin
- Proto-Oncogene Proteins c-akt
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Topics |
- Animals
- Apoptosis
- Biological Transport
- Cell Survival
- Cells, Cultured
- Dose-Response Relationship, Drug
- Female
- Gene Expression Regulation
- Lipoproteins, LDL
(blood, metabolism)
- Lysophosphatidylcholines
(pharmacology)
- Macrophages
(metabolism)
- Macrophages, Peritoneal
(cytology, metabolism)
- Male
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Oxidation-Reduction
- Phenotype
- Proto-Oncogene Proteins c-akt
(metabolism)
- RNA, Messenger
(genetics, metabolism)
- Scavenger Receptors, Class E
(deficiency, genetics, metabolism)
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