Abstract
Introduction
Phosphatases are redox regulated and play important roles in inflammatory signaling. Protein phosphatase 2A (PP2A) activity can be modified by reactive oxygen species (ROS) produced by numerous stimuli, including cigarette smoke (CS).
Aims and objectives
We examined whether the alteration of an anti-oxidant, glutathione peroxidase-1 (GPx-1), in mice could affect phosphatase response against CS and impact on CS-induced emphysema.
Methods
Wild-type, GPx-1 overexpressing and knockout mice were exposed to short and long term cigarette smoke. Inflammatory responses and phosphatase activities were determined from lung tissue.
Results
Over-expression of GPx-1 protected CS-induced inflammation and airway enlargement. Knockdown of GPx-1 resulted in an exaggerated emphysema phenotype, correlating with low PP2A activity levels. Induction of PP2A activity coincided with increased protein tyrosine phosphatase 1B (PTP1B) activity and subsequent tyrosine dephosphorylation of the catalytic subunit of PP2A (Tyr307).
Conclusions
Therefore, PP2A is redox regulated by GPx-1 and contributes to the inflammatory and proteolytic responses that occur in CS driven diseases. Targeting the PP2A pathway may be effective means of treating COPD and other diseases where inflammation plays a central role.
- © 2012 ERS
