Paraoxonase 1‐treated oxLDL promotes cholesterol efflux from macrophages by stimulating the PPARγ–LXRα–ABCA1 pathway. Issue 11 (23rd May 2016)

• Record Type: Journal Article
• Authors: Ikhlef, Souade; Berrougui, Hicham; Kamtchueng Simo, Olivier; Khalil, Abdelouahed
• Is Part Of: FEBS letters. Volume 590:Issue 11(2016)
• Page Start: 1614
• Page End: 1629
• Publication Date: 2016-05-23
• Subjects: cholesterol efflux -- LysoPC -- PON1 -- reverse cholesterol transport; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1002/1873-3468.12198
• Languages: English
• ISSNs: 0014-5793

Abstract

Abstract : 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 PPARγ and LXRα 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. Abstract :