Department of Radiation Oncology, Duke University Medical Center, Durham, NC, USA.
Int J Radiat Oncol Biol Phys. 2012 Jun 1;83(2):740-8. doi: 10.1016/j.ijrobp.2011.08.005. Epub 2012 Jan 21.
Apoptosis in irradiated normal lung tissue has been observed several weeks after radiation. However, the signaling pathway propagating cell death after radiation remains unknown.
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.
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-β1, 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.
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.
在接受放射治疗数周后，人们已经观察到放射治疗后的正常肺组织中的细胞凋亡。然而，导致细胞死亡的信号通路在放射后仍然未知。
用 15Gy 对 C57BL/6J 小鼠全胸进行照射。在放射后 6 周，用或不用 AEOL10150（一种活性氧和氮物种的有效催化清除剂）来评估促凋亡信号。
凋亡主要发生在 I 型和 II 型肺泡上皮细胞和内皮细胞中。凋亡与 PTEN 表达增加、下游 PI3K/AKT 信号通路抑制以及 p53 和 Bax 蛋白水平增加相关。转化生长因子-β1、Nox4 和氧化应激在放射后 6 周也增加。AEOL10150 的治疗性给药抑制了促凋亡信号，并显著减少了凋亡细胞的数量。
放射后 PTEN 信号的增加导致肺实质细胞凋亡。我们假设 Nox4 衍生的氧化应激会影响 PTEN 的上调。据我们所知，这是首次强调 PTEN 在放射诱导的肺毒性中的作用的研究。
