title: Glutathione peroxidase-1 as a novel therapeutic target for COPD.
abstract: Oxidative stress plays a role in a variety of diseases but it is even more pertinent in chronic obstructive pulmonary disease (COPD) given the increased oxidant burden in smokers. The increased oxidant burden results from the fact that cigarette smoke contains over 4700 different chemical compounds and more than 10(15) oxidants/free radicals per puff. Other factors, such as air pollutants, infections, and occupational dusts that may exacerbate COPD, also have the potential to produce oxidative stress. These oxidants give rise to Reactive Oxygen Species (ROS) that are generated enzymatically by inflammatory and epithelial cells within the lung as part of an inflammatory immune response towards a pathogen or irritant. Thus, while ROS are necessary for host defence against invading pathogens, increased levels of ROS have been implicated in initiating inflammatory responses in the lungs through the activation of transcriptional factors, signal transduction pathways, chromatin remodelling and gene expression of pro-inflammatory mediators. However, the normal lung has developed defences to ROS-mediated damage, which include antioxidant enzymes such as superoxide dismutase, catalase, and glutathione peroxidase. In this review we consider the therapeutic potential of the antioxidant enzyme glutathione peroxidase-1 for the treatment of cigarette smoke-induced lung inflammation and damage.
authors.affiliation: The University of Melbourne, Parkville, Australia. rossv@unimelb.edu.au
authors.forename: Ross
authors.initials: R
authors.lastname: Vlahos
authors.forename: Steven
authors.initials: S
authors.lastname: Bozinovski
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D001393:Azoles / Q000627:therapeutic use*; D005979:Glutathione Peroxidase / Q000627:therapeutic use*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D054833:Isoindoles; D008168:Lung / Q000378:metabolism; D008665:Metalloporphyrins / Q000627:therapeutic use; D016566:Organoselenium Compounds / Q000627:therapeutic use*; D018384:Oxidative Stress; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012907:Smoking / Q000009:adverse effects*; D013482:Superoxide Dismutase / Q000627:therapeutic use; D014028:Tobacco Smoke Pollution / Q000009:adverse effects; D000094765:Glutathione Peroxidase GPX1
chemical_list: C472668:AEOL 10150; D000975:Antioxidants; D001393:Azoles; D054833:Isoindoles; D008665:Metalloporphyrins; D016566:Organoselenium Compounds; D017382:Reactive Oxygen Species; D014028:Tobacco Smoke Pollution; C042986:ebselen; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D000094765:Glutathione Peroxidase GPX1; C000722067:GPX1 protein, human