Conditional Radioresistance of tet-Inducible Manganese Superoxide Dismutase Bone Marrow Stromal Cell Lines

被引:10
作者
Epperly, Michael W. [1 ]
Chaillet, J. Richard [2 ,3 ,4 ]
Kalash, Ronny [1 ]
Shaffer, Ben [2 ,3 ,4 ]
Goff, Julie [1 ]
Franicola, Darcy [1 ]
Zhang, Xichen [1 ]
Dixon, Tracy [1 ]
Houghton, Frank [1 ]
Wang, Hong [1 ]
Berhane, Hebist [1 ]
Romero, Cynthia [1 ]
Kim, Jee-Hong [1 ]
Greenberger, Joel S. [1 ]
机构
[1] Univ Pittsburgh, Sch Med, Dept Radiat Oncol, Pittsburgh, PA 15232 USA
[2] Univ Pittsburgh, Sch Med, Dept Microbiol, Pittsburgh, PA 15232 USA
[3] Univ Pittsburgh, Sch Med, Dept Mol Genet, Pittsburgh, PA 15232 USA
[4] Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15232 USA
关键词
RADIATION-INDUCED APOPTOSIS; GENE-THERAPY; IONIZING-RADIATION; INTRATRACHEAL INJECTION; PULMONARY-FIBROSIS; OXIDATIVE STRESS; NRF2; PROTECTS; KAPPA-B; IRRADIATION; MICE;
D O I
10.1667/RR3177.1
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Mitochondrial targeted manganese superoxide dismutase is a major antioxidant enzyme, the levels of which modulate the response of cells, tissues and organs to ionizing irradiation. We developed a Tet-regulated MnSOD mouse (MnSODtet) to examine the detailed relationship between cellular MnSOD concentration and radioresistance and carried out in vitro studies using bone marrow culture derived stromal cell lines (mesenchymal stem cells). Homozygous MnSODtet/tet cells had low levels of MnSOD, reduced viability and proliferation, increased radiosensitivity, elevated overall antioxidant stores, and defects in cell proliferation and DNA strand-break repair. Doxycycline (doxy) treatment of MnSODtet/tet cells increased MnSOD levels and radioresistance from n = of 2.79 +/- 1.04 to 8.69 +/- 1.09 (P = 0.0060) and normalized other biologic parameters. In contrast, MnSODtet/tet cells showed minimal difference in baseline and radiation induced mRNA and protein levels of TGF-beta, Nrf2 and NF-kappa B and radiation induced cell cycle arrest was not dependent upon MnSOD level. These novel MnSODtet/tet mouse derived cells should be valuable for elucidating several parameters of the oxidative stress response to ionizing radiation. (C) 2013 by Radiation Research Society
引用
收藏
页码:189 / 204
页数:16
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