Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases Co-constructed by Henan Province & Education Ministry of P.R. China, Henan University of Chinese Medicine, Zhengzhou, China; Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese Medicine, Zhengzhou, China; Henan Research Center for Special Processing Technology of Chinese Medicine, School of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, China.
Henan Research Center for Special Processing Technology of Chinese Medicine, School of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, China.
Food Chem Toxicol. 2021 Apr;150:112050. doi: 10.1016/j.fct.2021.112050. Epub 2021 Feb 10.
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 HO 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 Cysand Cys, similar to HO. 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.
慢性阻塞性肺疾病（COPD）是一种全球性的公共卫生问题，到 2020 年将成为全球第三大致死原因。磷酸酶和张力蛋白同源物缺失的第 10 号染色体（PTEN）是一种双特异性蛋白和脂质磷酸酶，在 COPD 中发挥着重要作用。然而，PTEN 在 COPD 发展过程中的氧化还原调节作用研究甚少。我们的研究结果表明，香烟烟雾提取物（CSE）可使 BEAS-2B 细胞中的 PTEN 发生时间依赖性氧化，而 CSE 暴露引起的 PTEN 氧化比 HO 延迟。此外，我们发现 NADPH 氧化酶的 DUOX1 和 2 产生的 ROS 主要负责氧化失活 PTEN，同时也导致 Trx-1 二聚化失活。CSE 暴露诱导的 PTEN 氧化机制是通过半胱氨酸之间形成二硫键介导的，类似于 HO。PTEN 的失活导致 Akt 的磷酸化增加。总之，CSE 暴露可增加细胞内 ROS，主要来自 DUOX1 和 2，从而氧化 PTEN 和 Trx-1，导致 Akt 激活，最终导致 COPD 的发生，提示 PTEN 是 COPD 新疗法的潜在靶点。
