Di-oleoyl phosphatidylcholine (PC-18:1) stimulates paraoxonase 1 (PON1) enzymatic and biological activities: In vitro and in vivo studies

Abstract

Objective Paraoxonase 1 (PON1) is a high-density lipoprotein (HDL)-associated enzyme which possess anti-atherogenic properties. Our aim was to analyze the effect of HDL phospholipids on HDL-associated paraoxonase (PON1) catalytic and biological activities. Methods and results In HDL isolated from di-oleoyl-phosphatidylcholine (PC-18:1)-enriched serum, HDL–PC-18:1 levels, as well as PON1 lactonase, arylesterase and paraoxonase activities were increased by 23%, 35%, 47% and 63%, respectively, as compared to control HDL ( p < 0.01). Furthermore, PON1 contribution to HDL-mediated cholesterol efflux from J774A.1 macrophages was higher in PC-18:1-enriched HDL in comparison to control HDL. In vivo olive oil consumption by Balb C mice increased HDL phospholipids/protein (30%), and HDL–PON1 arylesterase (150%) and lactonase (94%) activities ( p < 0.01). Furthermore, in the olive oil-treated mice PON1 contribution to HDL-mediated macrophage cholesterol efflux was higher by 100%, in comparison to placebo mouse HDL ( p < 0.01). Similarly, olive oil consumption by healthy subjects increased HDL–PC-18:1 levels, HDL–PON1 arylesterase (88%), lactonase (52%), paraoxonase (140%) activities and PON1 stimulatory effect on HDL-mediated cholesterol efflux (53%) as compared to HDL before treatment ( p < 0.01). PC-18:1 stimulatory effect on recombinant PON1 mutant (lacks 20 amino acids at the N-terminal region) paraoxonase and lactonase activities was lower by 56% and 57%, respectively, in comparison to its effect on wild type PON1 ( p < 0.01). Conclusion Intervention to increase PON1 activities by HDL enrichment with PC-18:1 could be proven as a beneficial anti-atherogenic therapy.