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Publication : Paraoxonase 1-treated oxLDL promotes cholesterol efflux from macrophages by stimulating the PPARγ-LXRα-ABCA1 pathway.

First Author  Ikhlef S Year  2016
Journal  FEBS Lett Volume  590
Issue  11 Pages  1614-29
PubMed ID  27148853 Mgi Jnum  J:233832
Mgi Id  MGI:5788200 Doi  10.1002/1873-3468.12198
Citation  Ikhlef S, et al. (2016) Paraoxonase 1-treated oxLDL promotes cholesterol efflux from macrophages by stimulating the PPARgamma-LXRalpha-ABCA1 pathway. FEBS Lett 590(11):1614-29
abstractText  Here, we investigate the mechanism through which paraoxonase 1 (PON1) may regulate cholesterol efflux. Pretreatment of oxLDL with PON1 (oxLDL-PON1) contributed to the formation of LysoPC. In J774 macrophages, oxLDL-PON1 increased cholesterol efflux by more than 47% compared to oxLDL alone. oxLDL-PON1 significantly increased mRNA and protein expression of ABCA1 and ABCG1, as well as of PPARgamma and LXRalpha compared to oxLDL alone. Intraperitoneal injection of oxLDL-PON1- or LysoPC-treated J774 macrophages significantly increased the fecal elimination of macrophage-derived cholesterol in these mice. Our results suggest that PON1 stimulates cholesterol efflux via a mechanism that involves oxidized phospholipid hydrolysis.
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