Glutathione peroxidase-1 as a novel therapeutic target for COPD

Figures & data

Figure 1. Sources and production of ROS in the lung. Activation of macrophages, neutrophils, and epithelium by cigarette smoke generates superoxide radicals (O₂^•−) which can then either react with nitric oxide (NO) to form reactive peroxynitrite molecules (ONOO⁻) or alternatively be rapidly converted to damaging hydrogen peroxide (H₂O₂) under the influence of SOD. This in turn can result in the non-enzymatic production of damaging hydroxyl radical (^•OH) from H₂O₂ in the presence of Fe²⁺. H₂O₂ is subsequently enzymatically reduced by glutathione peroxidases (Gpxs), including Gpx-1, as well as catalase (CAT). Gpx-1 uses GSH as a cofactor to reduce H₂O₂, resulting in the formation of oxidized glutathione (GSSG), which can then be reduced to GSH by glutathione reductase (GR). The ROS O₂^•−, ONOO⁻, H₂O₂, and ^•OH can then cause lung inflammation, DNA damage, protein denaturation, lipid peroxidation, and emphysema.