Recombinant Rat Serum paraoxonase/arylesterase 2 (PON2) is an enzyme that, in rats, is involved in antioxidant defense, lipid metabolism, and the regulation of inflammation . PON2 is part of the paraoxonase family of enzymes, which also includes PON1 and PON3 . These enzymes are known for their ability to hydrolyze lactones, aromatic esters, and organophosphates . PON2 is the oldest member of this family and acts as a potent quorum quencher .
PON2 is primarily located intracellularly, which sets it apart from PON1 and PON3, which are secreted extracellularly . It has calcium-dependent hydrolytic activity on lactones, esters, and aryl esters . PON2 also functions as an antioxidant enzyme, reducing the oxidative state of cells and preventing cell-mediated oxidation of low-density lipoprotein (LDL) . Unlike PON1 and PON3, PON2 does not typically show hydrolytic activity toward phosphotriesters, although some activity has been reported for a mutated recombinant version .
PON2's overexpression can lower the oxidative state within cells, which prevents and reverses the oxidative modification of LDLs . This action blocks the ability of mildly oxidized LDL to induce monocyte chemotaxis, thereby exerting an antiapoptotic effect by reducing levels of reactive oxygen species (ROS) .
PON2 plays a crucial role in innate immunity, particularly in defense against bacterial infections . It exhibits high specific activity against N-(3-oxododecanoyl)-L-homoserine lactone (3OC12-HSL), a key quorum sensing signal in B. aeruginosa . By hydrolyzing 3OC12-HSL, PON2 interferes with bacterial communication, disrupting biofilm formation and reducing the expression of virulence factors . Studies using PON2 knockout mice have shown a reduced ability to counteract B. aeruginosa infection, further supporting its role in defense against bacterial pathogens .
The activity of PON2 can be modulated by various factors, including post-translational modifications . For instance, the increased intracellular Ca2+ downregulates PON2 mRNA, protein, and hydrolytic activity . Ubiquitination at position 144 has been identified as one modification responsible for 3OC12-HSL-mediated PON2 inactivation, suggesting a mechanism by which bacteria can modulate enzyme activity to protect themselves .