Paraoxonases-2 and -3 Are Important Defense Enzymes against Pseudomonas aeruginosa Virulence Factors due to Their Anti-Oxidative and Anti-Inflammatory Properties.

Journal of Lipids
Eva-Maria SchweikertSven Horke

Abstract

The pathogen Pseudomonas aeruginosa causes serious damage in immunocompromised patients by secretion of various virulence factors, among them the quorum sensing N-(3-oxododecanoyl)-L-homoserine lactone (3OC12) and the redox-active pyocyanin (PCN). Paraoxonase-2 (PON2) may protect against P. aeruginosa infections, as it efficiently inactivates 3OC12 and diminishes PCN-induced oxidative stress. This defense could be circumvented because 3OC12 mediates intracellular Ca(2+)-rise in host cells, which causes rapid inactivation and degradation of PON2. Importantly, we recently found that the PON2 paralogue PON3 prevents mitochondrial radical formation. Here we investigated its role as additional potential defense mechanism against P. aeruginosa infections. Our studies demonstrate that PON3 diminished PCN-induced oxidative stress. Moreover, it showed clear anti-inflammatory potential by protecting against NF-κB activation and IL-8 release. The latter similarly applied to PON2. Furthermore, we observed a Ca(2+)-mediated inactivation and degradation of PON3, again in accordance with previous findings for PON2. Our results suggest that the anti-oxidative and anti-inflammatory functions of PON2 and PON3 are an important part of our innate ...Continue Reading

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Citations

Sep 10, 2013·Neurotoxicology·Lucio G CostaClement E Furlong
Sep 23, 2014·Atherosclerosis·Huige LiUlrich Förstermann
May 31, 2016·Chemico-biological Interactions·Clement E FurlongLucio G Costa
Apr 20, 2016·Infection and Immunity·Brahmchetna BediRuxana T Sadikot
Aug 19, 2020·Journal of Veterinary Diagnostic Investigation : Official Publication of the American Association of Veterinary Laboratory Diagnosticians, Inc·Gabriele RossiSaverio Paltrinieri
Jun 24, 2016·European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology·S IftimieA Castro
Oct 26, 2018·Toxicology·Efthimios DardiotisAristidis Tsatsakis
Feb 11, 2021·Antioxidants·Giuseppe MancoTeresa Maria Carusone
Jun 30, 2021·Biochimie·Kristyna Krasulova, Peter Illes

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Methods Mentioned

BETA
transfection
FCS
ELISArray
ELISA
PCR

Software Mentioned

GraphPad Prism

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