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Selective uptake and efflux of cholesteryl linoleate in LDL by macrophages expressing 12/15-lipoxygenase

Journal Article · · Biochemical and Biophysical Research Communications
DOI:https://doi.org/10.1016/J.BBRC.2005.0· OSTI ID:20793189
 [1];  [2];  [2];  [3];  [4];  [4];  [2]
  1. Department of Nutritional Science, Faculty of Health and Welfare Science, Okayama Prefectural University, Soja, Okayama 719-1197 (Japan)
  2. Department of Molecular Pharmacology, Kanazawa University Graduate School of Medical Science, Kanazawa 920-8640 (Japan)
  3. Department of Molecular Function Analysis, Kanazawa University Graduate School of Medical Science, Kanazawa 920-8640 (Japan)
  4. Research Department, R and D Center, BML, Inc., Saitama 350-1101 (Japan)
Oxidation of low density lipoprotein (LDL) is a critical step for airtightness, and the role of the 12/15-lipoxygenase (12/15-Lox) as well as LDL receptor-related protein (Lp) expressed in macrophages in this process has been suggested. The oxygenation of cholesteryl linoleate in LDL by mouse macrophage-like Joe.1 cells over expressing 12/15-Lox was inhibited by an anti-Lp antibody but not by an anti-LDL receptor antibody. When the cells were incubated with LDL double-labeled by [{sup 3}H]cholesteryl linoleate and [{sup 125}I]apo B, association with the cells of [{sup 3}H]cholesteryl linoleate expressed as LDL protein equivalent exceeded that of [{sup 125}I]apo B, indicating selective uptake of [{sup 3}H]cholesteryl linoleate from LDL to these cells. An anti-Lp antibody inhibited the selective uptake of [{sup 3}H]cholesteryl ester by 62% and 81% with the 12/15-Lox-expressing cells and macrophages, respectively. Furthermore, addition of LDL to the culture medium of the [{sup 3}H]cholesteryl linoleate-labeled 12/15-Lox-expressing cells increased the release of [{sup 3}H]cholesteryl linoleate to the medium in LDL concentration- and time-dependent manners. The transport of [{sup 3}H]cholesteryl linoleate from the cells to LDL was also inhibited by an anti-Lp antibody by 75%. These results strongly suggest that Lp contributes to the LDL oxidation by 12/15-Lox in macrophages by selective uptake and efflux of cholesteryl ester in the LDL particle.
OSTI ID:
20793189
Journal Information:
Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 1 Vol. 338; ISSN BBRCA9; ISSN 0006-291X
Country of Publication:
United States
Language:
English