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Bis(monoacylglycero)phosphate reduces oxysterol formation and apoptosis in macrophages exposed to oxidized LDL.
Biochem Pharmacol. 2013 Mar 28. pii: S0006-2952(13)00217-7. doi: 10.1016/j.bcp.2013.03.017
Arnal-Levron M, Chen Y, Delton-Vandenbroucke I, Luquain-Costaz C
Abstract:
.....Little is known about the possible contribution of cell-generated oxysterols towards LDL-associated oxysterols in cellular accumulation of oxysterols and related apoptosis. Using both radiochemical and mass analyzes, we showed that oxLDL greatly enhanced oxysterol production by RAW macrophages in comparison with unloaded cells or cells loaded with native LDL. Most oxysterols were produced by non-enzymatic routes (7-ketocholesterol and 7α/β-hydroyxycholesterol) but enzymatically formed 7α-, 25- and 27-hydroxycholesterol were also quantified. Bis(monoacylglycero)phosphate (BMP) is a unique phospholipid preferentially found in late endosomes. We and others have highlighted the role of BMP in the regulation of intracellular cholesterol metabolism/traffic in macrophages. We here report that cellular BMP accumulation was associated with a significantly lower production of oxysterols upon oxLDL exposure. Of note, potent pro-apoptotic 7-ketocholesterol was the most markedly decreased. OxLDL-induced cell cytotoxicity and apoptosis were consistently attenuated in BMP-enriched cells. Taken together, our data suggest that BMP exerts a protective action against the pro-apoptotic effect of oxLDL via a reduced production of intracellular pro-apoptotic oxysterols.
PMID: 23542536
Tags: 7KC, oxysterols