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.
journal_name
Atherosclerosisjournal_title
Atherosclerosisauthors
Efrat M,Rosenblat M,Mahmood S,Vaya J,Aviram Mdoi
10.1016/j.atherosclerosis.2008.05.016subject
Has Abstractpub_date
2009-02-01 00:00:00pages
461-9issue
2eissn
0021-9150issn
1879-1484pii
S0021-9150(08)00337-7journal_volume
202pub_type
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