Open AccessRadioresistance of Serpinb3a−/− Mice and Derived Hematopoietic and Marrow Stromal Cell Lines
Author(s) -
Stephanie Thermozier,
Xichen Zhang,
Wen Chi Hou,
Renee Fisher,
Michael W. Epperly,
Bing Liu,
İvet Bahar,
Hong Wang,
Joel S. Greenberger
Publication year - 2019
Publication title -
radiation research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 124
eISSN - 1938-5404
pISSN - 0033-7587
DOI - 10.1667/rr15379.1
Subject(s) - bone marrow , radioresistance , stromal cell , haematopoiesis , biology , cancer research , progenitor cell , clonogenic assay , immunology , stem cell , apoptosis , cell culture , microbiology and biotechnology , genetics , biochemistry
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.