Bibliographic Details
| Title: |
Cigarette Smoking Blocks the Protective Expression of Nrf2/ARE Pathway in Peripheral Mononuclear Cells of Young Heavy Smokers Favouring Inflammation. |
| Authors: |
Garbin, Ulisse1, Pasini, Anna Fratta1, Stranieri, Chiara1, Cominacini, Mattia1, Pasini, Andrea1, Manfro, Stefania1, Lugoboni, Fabio2, Mozzini, Chiara1, Guidi, GianCesare3, Faccini, Giovanni3, Cominacini, Luciano1 luciano.cominacini@univr.it |
| Source: |
PLoS ONE. 2009, Vol. 4 Issue 12, p1-12. 12p. |
| Subject Terms: |
*SMOKING, *CIGARETTE smokers, *ATHEROSCLEROSIS, *INFLAMMATION, *OXIDATIVE stress, *BLOOD vessels, *PHOSPHOLIPIDS, *GENE expression |
| Abstract: |
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-κB 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-κB and CRP (p<0.01). In in vitro studies oxPAPC dose-dependently increased NF-κB 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-κB that in turn may participate in the negative regulation of Nrf2/ARE pathway favouring inflammation. [ABSTRACT FROM AUTHOR] |
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| Database: |
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