Comparison of the ability of paraoxonases 1 and 3 to attenuate the in vitro oxidation of low-density lipoprotein and reduce macrophage oxidative stress.

In light of recent conflicting results regarding the antiatherogenic properties of the paraoxonase (PON) multigene family we have reexamined these properties in vitro. The abilities of recombinant human PON1 and PON3 to retard LDL oxidation, prevent macrophage oxidative stress, and promote macrophage cholesterol efflux were investigated. Both PON1 and PON3 retarded the oxidation of LDL; PON1 was significantly more efficient (50 and 100% at 20 microg PON3 and PON1, respectively (P<0.001)). Neither PON1 nor PON3 were able to prevent macrophage oxidative stress; however, both were able to retard macrophage-induced LDL oxidation (100 and 50% at 20 microg/ml respectively for PON1 and PON3, P<0.05). PON3 promoted macrophage cholesterol efflux (30% at 40 microg/ml, P<0.01); however, PON1 was found to be cytotoxic to the macrophages derived from the human monocyte THP-1 cell line. In conclusion using recombinant proteins we have been able to confirm some but not all of the antiatherosclerotic properties attributed to human PON1 and PON3 but have also discovered a novel cytotoxicity of PON1 toward macrophages derived from the human monocytic THP-1 cell line.