St. Reddy et al., Human paraoxonase-3 is an HDL-associated enzyme with biological activity similar to paraoxonase-1 protein but is not regulated by oxidized lipids, ART THROM V, 21(4), 2001, pp. 542-547
Paraoxonase-1 (PON1) is a secreted protein associated primarily with high d
ensity lipoprotein (HDL) and participates in the prevention of low density
lipoprotein (LDL) oxidation. Two other paraoxonase (PON) family members, na
mely, PON2 and PON3, have been identified. In this study, we report the clo
ning and characterization of the human PON3 gene from HepG2 cells. Tissue N
orthern analysis identifies an approximate to1.3-kb transcript for PON3 pri
marily in the liver. PON3-specific peptide antibodies detect an approximate
to 40-kDa protein associated with HDL and absent from LDL. Pretreatment of
cultured human aortic endothelial cells with supernatants from HeLa Tet On
cell lines overexpressing PON3 prevents the formation of mildly oxidized L
DL and inactivates preformed mildly oxidized LDL. In contrast to PON1, PON3
is not active against the synthetic substrates paraoxon and phenylacetate.
Furthermore, PON3 expression is not regulated in HepG2 cells by oxidized p
hospholipids and is not regulated in the livers of mice fed a high-fat athe
rogenic diet.