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PTEN deletion leads to deregulation of antioxidants and increased oxidative damage in mouse embryonic fibroblasts
Yan-Ying Huo1; Gang Li1; Rui-Feng Duan1; Qiao Gou2; Chun-Ling Fu2; Ying-Chun Hu1; Bo-Qiang Song3; Zhi-Hua Yang1; De-Chang Wu1; Ping-Kun Zhou1
2008
Source PublicationFREE RADICAL BIOLOGY AND MEDICINE
ISSN0891-5849
Volume44Issue:8Pages:1578-1591
Abstract

Despite the significance of oxidative damage in carcinogenesis, the molecular mechanisms that lead to increased susceptibility to oxidative stress are not well understood. We now report a link between loss of protection against oxidative damage and loss of function of PTEN, a highly mutated tumor suppressor gene in a variety of human tumors. Using two-dimensional gel electrophoresis, combined with Western and Northern blot analyses, we found that PTEN deficiency in mouse embryonic fibroblasts (MEFs) displays deregulated expression of several antioxidant enzymes, including peroxiredoxins 1, 2, 5, and 6 and Cu, Zn superoxide dismutase. In these Pten-deleted MEFs, the basal levels of reactive oxygen species (ROS) were increased, and both the basal level and the ROS-induced oxidative damage of DNA were increased, as evidenced by increased levels of hydrogen peroxide (H2O2), superoxide anion, 8-hydroxy-2′-deoxyguanosine, and DNA double-strand breaks. We further show that Pten deletion is correlated with resistance to H2O2-induced expression of several antioxidants. These findings suggest an essential role for PTEN in maintaining the normal redox state of mouse embryonic fibroblasts against oxidative damage. They also provide a molecular link between PTEN, whose inactivation is known to be involved in a variety of human tumors, and antioxidants, whose perturbation leads to oxidative damage of cells.

KeywordPten Reactive Oxygen Species Peroxiredoxin Cu Zn Superoxide Dismutase Oxidative Damage Free Radicals
DOIhttps://doi.org/10.1016/j.freeradbiomed.2008.01.013
Indexed BySCI
Language英语
WOS Research AreaBiochemistry & Molecular Biology ; Endocrinology & Metabolism
WOS SubjectBiochemistry & Molecular Biology ; Endocrinology & Metabolism
WOS IDWOS:000254925700008
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Cited Times [WOS]:27   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
Corresponding AuthorYan-Ying Huo
Affiliation1.a Department of Radiation Toxicology and Oncology, Beijing Institute of Radiation Medicine, Beijing 100850, People’s Republic of China
2.Department of Pathology, Chongqing University of Medical Science, Chongqing 400016, People’s Republic of China
3.The Affiliated Hospital of Academy of Military Medical Science, Beijing 100850, People’s Republic of China
Recommended Citation
GB/T 7714
Yan-Ying Huo,Gang Li,Rui-Feng Duan,et al. PTEN deletion leads to deregulation of antioxidants and increased oxidative damage in mouse embryonic fibroblasts[J]. FREE RADICAL BIOLOGY AND MEDICINE,2008,44(8):1578-1591.
APA Yan-Ying Huo.,Gang Li.,Rui-Feng Duan.,Qiao Gou.,Chun-Ling Fu.,...&Ping-Kun Zhou.(2008).PTEN deletion leads to deregulation of antioxidants and increased oxidative damage in mouse embryonic fibroblasts.FREE RADICAL BIOLOGY AND MEDICINE,44(8),1578-1591.
MLA Yan-Ying Huo,et al."PTEN deletion leads to deregulation of antioxidants and increased oxidative damage in mouse embryonic fibroblasts".FREE RADICAL BIOLOGY AND MEDICINE 44.8(2008):1578-1591.
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