Rabbit Anti-Human PON2 (a.a. 1-219) Polyclonal antibody

To achieve malignancy, cancer cells convert numerous signaling pathways, with evasion from cell death being a characteristic hallmark. The cell death machinery represents an anti-cancer target demanding constant identification of tumor-specific signaling molecules. Control of mitochondrial radical formation, particularly superoxide interconnects cell death signals with appropriate mechanistic execution. Superoxide is potentially damaging, but also triggers mitochondrial cytochrome c release. While paraoxonase (PON) enzymes are known to protect against cardiovascular diseases, recent data revealed that PON2 attenuated mitochondrial radical formation and execution of cell death. Another family member, PON3, is poorly investigated. Using various cell culture systems and knockout mice, here we addressed its potential role in cancer. PON3 is found overexpressed in various human tumors and diminishes mitochondrial superoxide formation. It directly interacts with coenzyme Q10 and presumably acts by sequestering ubisemiquinone, leading to enhanced cell death resistance. Localized to the endoplasmic reticulum (ER) and mitochondria, PON3 abrogates apoptosis in response to DNA damage or intrinsic but not extrinsic stimulation. Moreover, PON3 impaired ER stress-induced apoptotic MAPK signaling and CHOP induction. Therefore, our study reveals the mechanism underlying PON3's anti-oxidative effect and demonstrates a previously unanticipated function in tumor cell development. We suggest PONs represent a novel class of enzymes crucially controlling mitochondrial radical generation and cell death. Cell Death and Differentiation (2012) 19, 1549-1560; doi:10.1038/cdd.2012.35; published online 23 March 2012

The human paraoxonase (PON) gene family includes three members: PON1, PON2, and PON3. PON, which prevents the oxidative modification of lipoproteins, has been implicated as a potential risk factor of the cerebrovascular disease. In this study, we investigated associations between coding region single-nucleotide polymorphisms (cSNPs) of PON1, PON2, and PON3 genes and intracerebral hemorrhage (ICH) in a Korean population. Six cSNPs [rs13306698 and rs662 for PON1; rs12026 and rs7493 for PON2; rs13226149 and rs1053275 for PON3] were genotyped using direct sequencing in 145 ICH patients and 372 control subjects. Of the six cSNPs, rs12026 and rs7493, which were in complete linkage disequilibrium, were associated with ICH in log-additive (GC vs. CC vs. GG, p = 0.0008, OR = 0.53, 95 % CI = 0.36-0.78) and dominant models (GC/CC vs. GG, p = 0.0006, OR = 0.47, 95 % CI = 0.30-0.73). In addition, rs13226149 was associated with ICH in log-additive model (GA vs. AA vs. GG, p = 0.0033, OR = 0.58, 95 % CI = 0.39-0.84). In the allele frequency analysis, the C alleles of rs12026 and rs7493 and the A allele of rs13226149 were also shown to contribute to the decreased risk of ICH (p = 0.001, OR = 0.55, 95 % CI = 0.38-0.80 in rs12026 and rs7493; p = 0.003, OR = 0.58, 95 % CI = 0.40-0.83 in rs13226149). These results suggest that PON genes may be involved in the susceptibility of ICH.