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11 July 2019 Radioresistance of Serpinb3a−/− Mice and Derived Hematopoietic and Marrow Stromal Cell Lines
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Abstract

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.

©2019 by Radiation Research Society. All rights of reproduction in any form reserved.
Stephanie Thermozier, Xichen Zhang, Wen Hou, Renee Fisher, Michael W. Epperly, Bing Liu, Ivet Bahar, Hong Wang, and Joel S. Greenberger "Radioresistance of Serpinb3a−/− Mice and Derived Hematopoietic and Marrow Stromal Cell Lines," Radiation Research 192(3), 267-281, (11 July 2019). https://doi.org/10.1667/RR15379.1
Received: 8 March 2019; Accepted: 5 June 2019; Published: 11 July 2019
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