title: Paraoxonase 1-treated oxLDL promotes cholesterol efflux from macrophages by stimulating the PPARγ-LXRα-ABCA1 pathway.
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.
authors.affiliation: Research Centre on Aging, CSSS-IUGS, Sherbrooke, Canada.
authors.forename: Souade
authors.initials: S
authors.lastname: Ikhlef
authors.affiliation: Research Centre on Aging, CSSS-IUGS, Sherbrooke, Canada.|Department of Biology, University Sultan My Slimane, Beni Mellal, Morocco.
authors.forename: Hicham
authors.initials: H
authors.lastname: Berrougui
authors.affiliation: Research Centre on Aging, CSSS-IUGS, Sherbrooke, Canada.
authors.forename: Olivier
authors.initials: O
authors.lastname: Kamtchueng Simo
authors.affiliation: Research Centre on Aging, CSSS-IUGS, Sherbrooke, Canada.|Department of Medicine, Geriatrics Service, Faculty of Medicine and Biological Sciences, University of Sherbrooke, Canada.
authors.forename: Abdelouahed
authors.initials: A
authors.lastname: Khalil
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D043303:Aryldialkylphosphatase / Q000494:pharmacology / Q000502:physiology*; D001692:Biological Transport / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism* / Q000494:pharmacology*; D000071518:Liver X Receptors / Q000235:genetics* / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D047495:PPAR gamma / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics
chemical_list: D064286:ATP Binding Cassette Transporter 1; D008077:Lipoproteins, LDL; D000071518:Liver X Receptors; D047495:PPAR gamma; C099252:oxidized low density lipoprotein; D002784:Cholesterol; D043303:Aryldialkylphosphatase
keywords: LysoPC; PON1; cholesterol efflux; reverse cholesterol transport