|M.Sc Student||Efrat Michal|
|Subject||Dioleoyl Phosphatidylcholine (PC-18:1) Stimulates|
Paraoxonase 1 (PON1) Enzimatic and Biological
Activities: In Vitro and in Vivo Studies
|Department||Department of Medicine||Supervisor||Professor Emeritus Michael Aviram|
|Full Thesis text|
Objective: Paraoxonase 1 (PON1) is a high-density lipoprotein (HDL)-associated enzyme which possesses anti-atherogenic properties. Our aim was to analyze the effect of HDL phospholipids on HDL-associated 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.