Radioresistance of Serpinb3a-/- Mice and Derived Hematopoietic and Marrow Stromal Cell Lines.

Radioresistance of Serpinb3a-/- Mice and Derived Hematopoietic and Marrow Stromal Cell Lines.
Radiat Res. 2019 Jul 11;:
Authors: Thermozier S, Zhang X, Hou W, Fisher R, Epperly MW, Liu B, Bahar I, Wang H, Greenberger JS
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-β. Both irradiated Serpinb3a-/- mouse bone marrow stromal cell lines and plasma removed from total-body irradiated mice had decreased levels o...

Source: Radiation Research - July 10, 2019 Category: Physics Authors: Thermozier S, Zhang X, Hou W, Fisher R, Epperly MW, Liu B, Bahar I, Wang H, Greenberger JS Tags: Radiat Res Source Type: research