Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.1.79 (hormone-sensitive lipase)
 2,163 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pathogenic bacterium Pseudomonas aeruginosa uses acyl-HSL quorum-sensing signals to regulate genes controlling virulence and biofilm formation. We found that paraoxonase 1 (PON1), a mammalian lactonase with an unknown natural substrate, hydrolyzed the P. aeruginosa acyl-HSL 3OC12-HSL. In in vitro assays, mouse serum-PON1 was required and sufficient to degrade 3OC12-HSL. Furthermore, PON2 and PON3 also degraded 3OC12-HSL effectively. Serum-PON1 prevented P. aeruginosa quorum-sensing and biofilm formation in vitro by inactivating the quorum-sensing signal. Although 3OC12-HSL production by P. aeruginosa was important for virulence in a mouse sepsis model, Pon1-knock-out mice were paradoxically protected. These mice showed increased levels of PON2 and PON3 mRNA in epithelial tissues suggesting a possible compensatory mechanism. Thus, paraoxonase interruption of bacterial communication represents a novel mechanism to modulate quorum-sensing by bacteria. The consequences for host immunity are yet to be determined.
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PMID:Human and murine paraoxonase 1 are host modulators of Pseudomonas aeruginosa quorum-sensing. 1626 97

Human paraoxonase 1 (PON1) has broad substrate specificity and has been shown to protect against exposure to some organophosphorus (OP) insecticides due to its ability to hydrolyze toxic metabolites of some organophosphorothioate insecticides. PON1 status has been shown to be important in protecting against vascular disease, presumably due to the not-as-yet fully characterized role of the three PON proteins in modulating oxidative stress. More recently, all three PONs (1, 2, and 3) have been shown to inactivate the quorum sensing factor N-(3-oxododecanoyl)-L: -homoserine lactone (3OC12-HSL) of Pseudomonas. Expression of human PON1 in Drosophila demonstrated the importance of PON1 in resistance to Pseudomonas infection. Many studies have examined only DNA single nucleotide polymorphisms as possible risk factors for disease or exposures. For all of the known functions of PON1, the level of PON1 enzyme is important and, in some cases, also the Q192R polymorphism. A simple high throughput two-substrate assay/analysis, plotting rates of diazoxon hydrolysis vs. paraoxon hydrolysis, provided both PON1 levels and functional Q192R phenotype/genotype. We have developed a new two-substrate assay/analysis protocol that provides PON1 status without use of toxic OP substrates. Factors were determined for inter-converting rates of hydrolysis of different substrates.
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PMID:Paraoxonase 1 status as a risk factor for disease or exposure. 2022 68

Human paraoxonase 1 (PON1) is a high-density lipoprotein (HDL)-associated serum enzyme that exhibits a broad substrate specificity. In addition to protecting against exposure to some organophosphorus (OP) pesticides by hydrolyzing their toxic oxon metabolites, PON1 is important in protecting against vascular disease by metabolizing oxidized lipids. Recently, PON1 has also been shown to play a role in inactivating the quorum sensing factor N-(3-oxododecanoyl)-l-homoserine lactone (3OC12-HSL) of Pseudomonas aeruginosa. Native, untagged engineered recombinant human PON1 (rHuPON1) expressed in Escherichia coli and purified by conventional column chromatographic purification is stable, active, and capable of protecting PON1 knockout mice (PON1(-/-)) from exposure to high levels of the OP compound diazoxon. The bacterially derived rHuPON1 can be produced in large quantities and lacks the glycosylation of eukaryotic systems that can produce immunogenic complications when inappropriately glycosylated recombinant proteins are used as therapeutics. Previous studies have shown that the determination of PON1 status, which reveals both PON1(192) functional genotype and serum enzyme activity level, is required for a meaningful evaluation of PON1's role in risk of disease or exposure. We have developed a new two-substrate assay/analysis protocol that provides PON1 status without use of toxic OP substrates, allowing for use of this protocol in non-specialized laboratories. Factors were also determined for inter-converting rates of hydrolysis of different substrates. PON1 status also plays an important role in revealing changes in HDL-associated PON1 activities in male patients with Parkinson disease (PD). Immunolocalization studies of PONs 1, 2 and 3 in nearly all mouse tissues suggest that the functions of PONs 1 and 3 extend beyond the plasma and the HDL particle.
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PMID:Human PON1, a biomarker of risk of disease and exposure. 2033 54