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Protection against gamma-radiation injury by protein tyrosine phosphatase 1B
- Source :
- Redox Biology, Vol 17, Iss , Pp 213-223 (2018)
- Publication Year :
- 2018
- Publisher :
- Elsevier, 2018.
-
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. Keywords: Protein tyrosine phosphatase, Cell viability, Irradiation sensitivity, Lethality, p53
- Subjects :
- Medicine (General)
R5-920
Biology (General)
QH301-705.5
Subjects
Details
- Language :
- English
- ISSN :
- 22132317
- Volume :
- 17
- Issue :
- 213-223
- Database :
- Directory of Open Access Journals
- Journal :
- Redox Biology
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.135d9a4c81ed48b28432ccde574eb0b4
- Document Type :
- article
- Full Text :
- https://doi.org/10.1016/j.redox.2018.04.018