Serpins are a group of serine-proteases involved in multiple signal transduction pathways in mammalian cells. In particular, Serpinb3a is involved in the lysosomal necrosis cell death pathway with components that overlap with radiation-induced apoptosis. We investigated the radiation response of Serpinb3a−/− mice compared to Serpinb3a+/+ mice on the Balb/c background. Serpinb3a−/− mice showed significant radioresistance to a dose of 8.0 Gy total-body irradiation, compared to Serpinb3a+/+ Balb/c mice. Long-term bone marrow cultures from Serpinb3a−/− mice showed increased longevity. In clonogenic survival assays, fresh bone marrow hematopoietic progenitors, as well as clonal interleukin-3 (IL-3)-dependent hematopoietic progenitor and bone marrow stromal cell lines from Serpinb3a−/− mice were radioresistant. Serpinb3a−/− mouse bone marrow-derived stromal cell lines had increased baseline and postirradiation antioxidant capacity. Serpinb3a−/− bone marrow stromal cells showed increased radiation-induced RNA transcripts for MnSOD and p21, and decreased levels of p53 and TGF-b. Both irradiated Serpinb3a−/− mouse bone marrow stromal cell lines and plasma removed from total-body irradiated mice had decreased levels of expression of stress response and inflammation-associated proteins. Abrogation of Serpinb3a may be a potential new target for mitigation of radiation effects.
Radioresistance of Serpinb3a−/− Mice and Derived Hematopoietic and Marrow Stromal Cell Lines
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Stephanie Thermozier, Xichen Zhang, Wen Hou, Renee Fisher, Michael W. Epperly, Bing Liu, Ivet Bahar, Hong Wang, Joel S. Greenberger; Radioresistance of Serpinb3a−/− Mice and Derived Hematopoietic and Marrow Stromal Cell Lines. Radiat Res 1 September 2019; 192 (3): 267–281. doi: https://doi.org/10.1667/RR15379.1
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