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Paraoxonase 1‐treated ox LDL promotes cholesterol efflux from macrophages by stimulating the PPAR γ– LXR α– ABCA 1 pathway
Author(s) -
Ikhlef Souade,
Berrougui Hicham,
Kamtchueng Simo Olivier,
Khalil Abdelouahed
Publication year - 2016
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.12198
Subject(s) - chemistry , cholesterol , efflux , liver x receptor , microbiology and biotechnology , biochemistry , biology , nuclear receptor , transcription factor , gene
Here, we investigate the mechanism through which paraoxonase 1 ( PON 1) may regulate cholesterol efflux. Pretreatment of ox LDL with PON 1 (ox LDL – PON 1) contributed to the formation of Lyso PC . In J774 macrophages, ox LDL – PON 1 increased cholesterol efflux by more than 47% compared to ox LDL alone. ox LDL – PON 1 significantly increased mRNA and protein expression of ABCA 1 and ABCG 1, as well as of PPAR γ and LXR α compared to ox LDL alone. Intraperitoneal injection of ox LDL – PON 1‐ or Lyso PC ‐treated J774 macrophages significantly increased the fecal elimination of macrophage‐derived cholesterol in these mice. Our results suggest that PON 1 stimulates cholesterol efflux via a mechanism that involves oxidized phospholipid hydrolysis.