Very low density lipoproteins provide a vector for secretion of paraoxonase-1 from cells.

Paraoxonase-1 (PON1) requires a suitable acceptor complex for its secretion from producing cells. The serum lipoprotein, high-density lipoprotein (HDL) has been shown to accomplish this function, whereas low-density lipoproteins are ineffective. The present study examined the influence of the third serum lipoprotein subclass, very low density lipoproteins (VLDL), on PON1 secretion. VLDL were shown to promote secretion of PON1 from a transfected Chinese hamster ovary model and from transfected hepatocytes in a high-affinity, saturable manner. The effects of HDL and VLDL were not additive, suggesting that they may employ a common secretion pathway. VLDL was able to stabilise secreted PON1 enzyme activity, but less effectively than stabilisation by HDL. Following co-incubation of VLDL and HDL, the majority of PON1 accumulated in HDL even if HDL was added after initial association of the enzyme with VLDL. VLDL to HDL transfer of PON1 was rapid and did not require lipolysis of VLDL. Low levels of active PON1 were associated with VLDL in human serum, and VLDL-associated enzyme activity was proportional to serum triglyceride concentrations. Serum triglycerides were positively associated with whole serum PON1 mass but negatively associated with specific activity. PON1-enriched VLDL was more resistant to oxidation in vitro. The present study suggests that the triglyceride transport vector, VLDL, can modulate PON1 metabolism and activity. This is due, in part, to an influence of the lipoprotein on PON1 secretion. PON1 was associated with VLDL in human serum, where triglycerides correlated independently with variations in serum mass and activity of the enzyme. VLDL-associated PON1 exerted an anti-oxidative effect, which may be of physiological benefit.