The lung is a unique organ in terms of its direct exposure to high levels of
oxygen and reactive compounds. Several parenchymal
lung diseases (e.g.
emphysema associated with smoking and a number of fibrotic lung disorders) have been proposed to be due to the exposure of the lung to exogenous irritants leading to local redox imbalance in the alveolar epithelium. The
disease progression of
emphysema/
chronic obstructive pulmonary disease (
COPD) and
fibrosis share several common factors, such as the role of
reactive oxygen species, disturbances of the pulmonary
thiol status and activation of
growth factors and tissue destructing
proteases. Importantly in
COPD or
fibrosis, medication does not provide any significant
therapeutic effect. This review concentrates on the key
thiol (-SH)-regulated mechanisms leading to the development of
COPD and/or
pulmonary fibrosis and the major redox-regulated defense/
oxidant repair mechanisms,
thioredoxin/
peroxiredoxin and
glutaredoxin protein families in the lung. Redox-regulated
proteins, both
proteases and
oxidant repair
enzymes, undergo conformational changes during oxidative stress, a process that modulates their activation or inactivation. In addition, some of the redox-regulated
proteins influence the metabolism of
glutathione (GSH), a major small molecular
antioxidant of human lung, and participate in the crosstalk between numbers of GSH associated
enzymes functioning in the detoxification pathways of human lung. An understanding of the processes involved in
oxidant-mediated lung damage may provide the key to devising interventional strategies that can actually prevent the progression of lung parenchymal disease.