- 作者：Yu Zhang&lowast ; ; Xiuwu Zhang ; M.D. ; Ph.D.&lowast ; ; Zahid N. Rabbani ; M.D.&lowast ; ; Isabel L. Jackson ; B.S.&dagger ; ; Zeljko Vujaskovic ; M.D. ; Ph.D.&lowast ; ; &dagger ; ; vujas@radonc.duke.edu
- 关键词：Radiation ; Apoptosis ; Reactive oxygen species ; PTEN ; Nox4
- 刊名：International Journal of Radiation Oncology*Biology*Physics
- 出版年：2012
- 期刊代码：136_03603016
- 类别：med
- 出版时间：1 June, 2012
- 卷：83
- 期：2
- 页码：740-748
- 文件大小：2117 K
Purpose
Apoptosis in irradiated normal lung tissue has been observed several weeks after radiation. However, the signaling pathway propagating cell death after radiation remains unknown.Methods and Materials
C57BL/6J mice were irradiated with 15 Gy to the whole thorax. Pro-apoptotic signaling was evaluated 6 weeks after radiation with or without administration of AEOL10150, a potent catalytic scavenger of reactive oxygen and nitrogen species.
Results
Apoptosis was observed primarily in type I and type II pneumocytes and endothelium. Apoptosis correlated with increased PTEN expression, inhibition of downstream PI3K/AKT signaling, and increased p53 and Bax protein levels. Transforming growth factor-尾1, Nox4, and oxidative stress were also increased 6 weeks after radiation. Therapeutic administration of AEOL10150 suppressed pro-apoptotic signaling and dramatically reduced the number of apoptotic cells.
Conclusion
Increased PTEN signaling after radiation results in apoptosis of lung parenchymal cells. We hypothesize that upregulation of PTEN is influenced by Nox4-derived oxidative stress. To our knowledge, this is the first study to highlight the role of PTEN in radiation-induced pulmonary toxicity.