Cigarette smoke extract amplifies NADPH oxidase-dependent ROS production to inactivate PTEN by oxidation in BEAS-2B cells

Chronic obstructive pulmonary disease (COPD) is widely recognized as a global public health problem and the third leading cause of mortality worldwide by 2020. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a dual-specificity protein and lipid phosphatase that plays an important role in COPD. However, the redox regulation of PTEN in the development of COPD was poorly studied. Our results showed that cigarette smoke extract (CSE) could oxidize PTEN in a time-dependent manner in BEAS-2B cells, whereas PTEN oxidation exposed to CSE was delayed compared to that of H2O2. Additionally, we found that ROS derived from DUOX1 and 2 of NADPH oxidases were mainly responsible for oxidative inactivation PTEN, also simultaneously led to Trx-1 inactivation by dimerization. Oxidative mechanism of PTEN exposed to CSE was mediated by forming a disulfide bond between Cys(71) and Cys(124), similar to H2O2. Inactivation of PTEN resulted in the increased phosphorylation of Akt. In conclusion, CSE exposure could elevate the intracellular ROS mainly from DUOX1 and 2 to oxidize PTEN and Trx-1 resulting in Akt activation, eventually cause the occurrence of COPD, suggesting that PTEN is a potential target for new therapies in COPD.

Automated summary

Overall, this study found that cigarette smoke extract (CSE) could oxidize PTEN in BEAS-2B cells, mainly through ROS from DUOX1 and 2 of NADPH oxidases leading to oxidative inactivation of PTEN and Trx-1, resulting in Akt activation and potentially contributing to the development of COPD. This suggests that PTEN could be a potential target for new therapies in COPD treatment.