دورية أكاديمية
Protection against gamma-radiation injury by protein tyrosine phosphatase 1B
العنوان: | Protection against gamma-radiation injury by protein tyrosine phosphatase 1B |
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المؤلفون: | Marina Mojena, María Pimentel-Santillana, Adrián Povo-Retana, Victoria Fernández-García, Silvia González-Ramos, Patricia Rada, Alberto Tejedor, Daniel Rico, Paloma Martín-Sanz, Angela M. Valverde, Lisardo Boscá |
المصدر: | Redox Biology, Vol 17, Iss , Pp 213-223 (2018) |
بيانات النشر: | Elsevier, 2018. |
سنة النشر: | 2018 |
المجموعة: | LCC:Medicine (General) LCC:Biology (General) |
مصطلحات موضوعية: | Medicine (General), R5-920, Biology (General), QH301-705.5 |
الوصف: | Protein tyrosine phosphatase 1B (PTP1B) is widely expressed in mammalian tissues, in particular in immune cells, and plays a pleiotropic role in dephosphorylating many substrates. Moreover, PTP1B expression is enhanced in response to pro-inflammatory stimuli and to different cell stressors. Taking advantage of the use of mice deficient in PTP1B we have investigated the effect of γ-radiation in these animals and found enhanced lethality and decreased respiratory exchange ratio vs. the corresponding wild type animals. Using bone-marrow derived macrophages and mouse embryonic fibroblasts (MEFs) from wild-type and PTP1B-deficient mice, we observed a differential response to various cell stressors. PTP1B-deficient macrophages exhibited an enhanced response to γ-radiation, UV-light, LPS and S-nitroso-glutathione. Macrophages exposed to γ-radiation show DNA damage and fragmentation, increased ROS production, a lack in GSH elevation and enhanced acidic β-galactosidase activity. Interestingly, these differences were not observed in MEFs. Differential gene expression analysis of WT and KO macrophages revealed that the main pathways affected after irradiation were an up-regulation of protein secretion, TGF-β signaling and angiogenesis among other, and downregulation of Myc targets and Hedgehog signaling. These results demonstrate a key role for PTP1B in the protection against the cytotoxicity of irradiation in intact animal and in macrophages, which might be therapeutically relevant. Keywords: Protein tyrosine phosphatase, Cell viability, Irradiation sensitivity, Lethality, p53 |
نوع الوثيقة: | article |
وصف الملف: | electronic resource |
اللغة: | English |
تدمد: | 2213-2317 |
Relation: | http://www.sciencedirect.com/science/article/pii/S2213231718301290; https://doaj.org/toc/2213-2317 |
DOI: | 10.1016/j.redox.2018.04.018 |
URL الوصول: | https://doaj.org/article/135d9a4c81ed48b28432ccde574eb0b4 |
رقم الأكسشن: | edsdoj.135d9a4c81ed48b28432ccde574eb0b4 |
قاعدة البيانات: | Directory of Open Access Journals |
تدمد: | 22132317 |
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DOI: | 10.1016/j.redox.2018.04.018 |