Cigarette Smoking Blocks the Protective Expression of Nrf2-ARE Pathway in Peripheral Mononuclear Cells of Young Heavy Smokers Favouring InflammationReportar como inadecuado




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Cigarette smoking is an important risk factor for atherosclerosis, a chronic inflammatory disease. However the underlying factors of this effect are unclear. It has been hypothesized that water-soluble components of cigarette smoke can directly promote oxidative stress in vasculature and blood cells. Aim of this study was to study the relationship between oxidative stress and inflammation in a group of young smokers. To do this we evaluated: 1 the oxidation products of phospholipids oxPAPC in peripheral blood mononuclear cells PBMC; 2 their role in causing PBMC reactive oxygen species ROS generation and changes in GSH; 3 the expression of the transcription factor NF-E2-related factor 2 Nrf2 and of related antioxidant genes ARE; 4 the activation of NF-kB and C-reactive protein CRP values. We studied 90 healthy volunteers: 32 non-smokers, 32 moderate smokers 5–10 cigarettes-day and 26 heavy smokers 25–40 cigarettes-day. OxPAPC and p47phox expression, that reasonably reflects NADPH oxidase activity, were higher in moderate smokers and heavy smokers than in non-smokers p<0.01, the highest values being in heavy smokers p<0.01. In in vitro studies oxPAPC increased ROS generation via NADPH oxidase activation. GSH in PBMC and plasma was lower in moderate smokers and heavy smokers than in non-smokers p<0.01, the lowest values being in heavy smokers p<0.01. Nrf2 expression in PBMC was higher in moderate smokers than in non-smokers p<0.01, but not in heavy smokers, who had the highest levels of NF-kB and CRP p<0.01. In in vitro studies oxPAPC dose-dependently increased NF-kB activation, whereas at the highest concentrations Nrf2 expression was repressed. The small interference si RNA-mediated knockdown of NF-κB-p65 increased about three times the expression of Nrf2 stimulated with oxPAPC. Cigarette smoke promotes oxPAPC formation and oxidative stress in PBMC. This may cause the activation of NF-kB that in turn may participate in the negative regulation of Nrf2-ARE pathway favouring inflammation.



Autor: Ulisse Garbin, Anna Fratta Pasini, Chiara Stranieri, Mattia Cominacini, Andrea Pasini, Stefania Manfro, Fabio Lugoboni, Chiara Mo

Fuente: http://plos.srce.hr/



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