| Oxidative Stress Mediates Radiation Lung Injury by Inducing Apoptosis. | |
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MedLine Citation:
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PMID: 22270165 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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-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. 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. |
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Authors:
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Yu Zhang; Xiuwu Zhang; Zahid N Rabbani; Isabel L Jackson; Zeljko Vujaskovic |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-1-21 |
Journal Detail:
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Title: International journal of radiation oncology, biology, physics Volume: - ISSN: 1879-355X ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-1-24 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7603616 Medline TA: Int J Radiat Oncol Biol Phys Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011 Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Radiation Oncology, Duke University Medical Center, Durham, NC. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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