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| Content Provider | Journal of Biological Chemistry (JBC) |
|---|---|
| Author | Rusiñol, Antonio E. Yang, Lin Thewke, Douglas Panini, Sankhavaram R. Kramer, Marianne F. Sinensky, Michael S. |
| Abstract | Oxidized low density lipoprotein (oxLDL) induces apoptosis in macrophages, smooth muscle cells, and endothelial cells. To elucidate the molecular mechanism of oxLDL-induced cytotoxicity and determine its tissue specificity, we have used Chinese hamster ovary (CHO)-K1 cells expressing human CD36 (CHO/CD36). Expression of CD36 rendered these cells susceptible to killing by oxLDL. This cytotoxicity was due to the induction of apoptosis. Therefore, CD36 expression is the only requirement for oxLDL-induced apoptosis. Oxysterols apparently mediate the cytotoxicity of oxLDL in macrophage foam cells and endothelial cells. 25-Hydroxycholesterol, at concentrations higher than 1 μg/ml, killed CHO-K1 cells, by apoptosis, in medium supplemented with serum as a source of cholesterol. These effects were not seen in a 25-hydroxycholesterol-resistant CHO/CD36 mutant (OXR), which was otherwise capable of undergoing apoptosis in response to staurosporine. This mutant was also resistant to killing by oxLDL, suggesting that oxysterols are at least partially responsible for the toxic effects of oxLDL. Oxysterol-induced apoptosis did not involve regulation of sterol regulatory element-binding protein proteolysis or the cholesterol biosynthetic pathway. 25-Hydroxycholesterol stimulated calcium uptake by CHO-K1 cells within 2 min after addition. Treatment of CHO or THP-1 (macrophage) cells with the calcium channel blocker nifedipine prevented 25-hydroxycholesterol induction of apoptosis. OXR showed no enhanced calcium uptake in response to 25-hydroxycholesterol. |
| Related Links | http://www.jbc.org/content/275/10/7296.abstract |
| Ending Page | 7303 |
| Starting Page | 7296 |
| Page Count | 8 |
| File Format | HTM / HTML PDF |
| ISSN | 00219258 |
| Journal | Journal of Biological Chemistry (JBC) |
| Issue Number | 10 |
| Volume Number | 275 |
| DOI | 10.1074/jbc.275.10.7296 |
| e-ISSN | 1083351X |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology |
| Publisher Date | 2000-03-10 |
| Access Restriction | Open |
| Subject Keyword | Oxidized low density lipoprotein (oxLDL) Low density lipoprotein (LDL) Sterol regulatory element (SRE) Sterol regulatory element-binding protein (SREBP) Chinese hamster ovary (CHO) Phosphate-buffered saline (PBS) 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI) Terminal deoxyuridine nick end labeling (TUNEL) 25-hydroxycholesterol (25-OHC) 7-amido-4-methylcoumarin (AMC) LIPIDS AND LIPOPROTEINS |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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