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http://hdl.handle.net/10553/41505
Title: | Protection against gamma-radiation injury by protein tyrosine phosphatase 1B | Authors: | Mojena, Marina Pimentel-Santillana, María Povo-Retana, Adrián Fernández-García, Victoria González-Ramos, Silvia Rada, Patricia Tejedor, Alberto Rico, Daniel Martín-Sanz, Paloma Valverde, Angela M. Boscá, Lisardo |
UNESCO Clasification: | 320502 Endocrinología | Keywords: | Protein tyrosine phosphatase Cell viability Irradiation sensitivity Lethality p53 |
Issue Date: | 2018 | Journal: | Redox Biology | Abstract: | 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. | URI: | http://hdl.handle.net/10553/41505 | ISSN: | 2213-2317 | DOI: | 10.1016/j.redox.2018.04.018 | Source: | Redox Biology [ISSN 2213-2317], v. 17, p. 213-223 |
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