International journal of radiation oncology, biology, physics · 2012
Oxidative stress mediates radiation lung injury by inducing apoptosis.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Zhang Yu, Zhang Xiuwu, Rabbani Zahid N, Jackson Isabel L, Vujaskovic Zeljko
Аннотация
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.
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.
Предметные рубрики MeSH
Alveolar Epithelial CellsAnimalsAntioxidantsApoptosisCaspase 3EndotheliumFemaleIn Situ Nick-End LabelingLungLung InjuryMetalloporphyrinsMiceMice, Inbred C57BLModels, AnimalNADPH Oxidase 4NADPH OxidasesOxidative StressPTEN PhosphohydrolasePhosphatidylinositol 3-KinasesProtein Serine-Threonine KinasesProto-Oncogene Proteins c-aktRadiation InjuriesRandom AllocationReactive Oxygen SpeciesSignal TransductionTime FactorsTransforming Growth Factor beta1Tumor Suppressor Protein p53Up-Regulationbcl-2-Associated X ProteinScaffold Protein ILK