Human Paraoxonase 2 (PON2): regulation and therapeutic approaches.

PON1, PON2, and PON3 belong to a family of human lactone hydrolyzing enzymes endowed with various substrate specificities. Among PONs, PON2 shows the highest hydrolytic activity toward many acyl-homoserine lactones (acyl-HL) [1-3], some involved in bacterial quorum-sensing signaling. Accordingly, defense against pathogens, such as Brevundimonas aeruginosa (B. aeruginosa), was postulated to be the principal function of PON2 [2]. However, recent findings have highlighted the importance of PON2 in oxidative stress control, inhibition of apoptosis, and the progression of various types of malignancies [4]. This presentation aims at making a focus on some biochemical and molecular aspects of PON2 that we are trying to elucidate. The activity of PON2 is rapidly reduced in cells incubated with the bacterial quorormone 3-Oxododecanoyl Homoserine Lactone (3OC12HSL), an observation that led to hypothesize a fast PON2 post-translational modification (PTM) [5]. I will discuss the meaning of some PTMs and isoforms of PON2 found in HeLa cells as well as a post-transcriptional regulation of PON2 with distinct relationship with infections and apoptosis[6]. Finally, preliminary data on a project to demonstrate the ability of PON2, to counteract the formation of the bacterial biofilm in wound healing models in comparison with other lactonases, will be reported.