Fig. 2

Molecular and cellular targets of reactive oxygen species (ROS) in the airways and lungs of COPD patients. ROS directly affects the activity and/or expression of redox-sensitive kinases, transcription factors, mitochondria, anti-oxidant pathways, iron (Fe) biology and innate immune systems such as complement and autoantibody production. Modulation of these processes promotes cell proliferation/survival and cellular senescence which is associated with enhanced inflammation. Enhanced oxidant pathways and reduced anti-oxidant activity affects mucosal defence against bacteria and viruses including reduced phagocytosis, whilst oxidative stress actions on catalase and Fe allow excess bacterial growth. ROS also causes post-translational modifications of DNA, RNA, lipids and proteins to affect cellular function and reveal neo-epitopes for auto-antibody induction. The generation of oxidised phospholipids (OxPLs) can further drive mitochondria dysregulation and activate the inflammasome. Abbreviations: AP-1: activator protein-1; ARE, anti-oxidant response element; ERK, extracellular signal-regulated kinase; ETC, electron transport chain; GSH, glutathione; GPX, glutathione peroxidase; GRX, glutaredoxins; HIF1α, hypoxia-Inducible Factor 1α; JAK-STAT, Janus kinase-signal transducer and activator of transcription; KEAP, Kelch-like ECH-associated protein; MEK, mitogen-activated extracellular signal-regulated kinase; mtDNA, mitochondrial DNA; NADPH, nicotinamide adenine dinucleotide phosphate; NF-κB, nuclear factor κB; NOS, nitric oxide synthase; Nrf2, Nuclear factor-erythroid factor 2-related factor 2; p38 MAPK, p38 mitogen activated protein kinase; PI3K, phosphoinositide 3-kinase; RNS, reactive nitrogen species; TRX, thioredoxins