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

被引:21
作者
Efrat, Michal [1 ]
Rosenblat, Mira [1 ]
Mahmood, Saeed
Vaya, Jacob
Aviram, Michael [1 ]
机构
[1] Rambam Med Ctr, Rappaport Family Inst Res Med Sci, Lipid Res Lab, Technion Fac Med, IL-31096 Haifa, Israel
关键词
Paraoxonase; 1; HDL; Di-oleoyl phosphatidylcholine; Lactonase activity; Macrophages; Cholesterol efflux; LOW-DENSITY-LIPOPROTEIN; FATTY-ACID-COMPOSITION; MACROPHAGE CHOLESTEROL EFFLUX; APOLIPOPROTEIN-A-I; SERUM PARAOXONASE; OXIDATIVE STRESS; ATHEROSCLEROSIS; HDL; MICE; BINDING;
D O I
10.1016/j.atherosclerosis.2008.05.016
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 until 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 J774AJ 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 HIM, (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
引用
收藏
页码:461 / 469
页数:9
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