Abstract
The bone marrow is one of the most radio-sensitive tissues. Accidental ionizing radiation exposure can damage mature blood cells and hematopoietic progenitor/stem cells, and mortality can result from hematopoietic insufficiency and infection. Ionizing radiation induces alterations in gene and protein expression in hematopoietic tissue. Here we investigated radiation effects on protein carbonylation, a primary marker for protein oxidative damage. C57BL/6 mice were either sham irradiated or exposed to 7.5 Gy 60Co (0.6 Gy/min) total body irradiation. Bone marrow was obtained 24 h post-irradiation. Two dimensional (2-D) gel electrophoresis and Oxyblot immunodetection were used to discover carbonylated proteins, and peptide mass fingerprinting was performed for identification. 2D gels allowed the detection of 13 carbonylated proteins in the bone marrow; seven of these were identified, with two pairs of the same protein. Baseline levels of carbonylation were found in 78 kDa glucose-related protein, heat shock protein cognate 71 KDa, actin, chitinase-like protein 3 (CHI3L1), and carbonic anhydrase 2 (CAII). Radiation increased carbonylation in four proteins, including CHI3L1 and CAII, and induced carbonylation of one additional protein (not identified). Our findings indicate that the profile of specific protein carbonylation in bone marrow is substantially altered by ionizing radiation. Accordingly, protein oxidation may be a mechanism for reduced cell viability.
Highlights
High dose total body irradiation may occur as the result of a nuclear accident or terrorist event.Radiotherapy is a common therapeutic modality for cancer treatment, including for leukemia and lymphoma
While loss of mature blood cells is a key factor in radiation morbidity, mortality is believed to occur due to prolonged myelosuppression from the loss of hematopoietic progenitor cells (HPC) and primitive hematopoietic stem cells (HSC) [2,3]
The present findings show that radiation exposure alters the profile of protein carbonylation in bone marrow to produce a biosignature for radiation injury
Summary
High dose total body irradiation may occur as the result of a nuclear accident or terrorist event. Experiments using qRT-PCR directed toward the detection of specific gene products associated with programmed cell death demonstrated increased expression of Bax and caspase-9 in total bone marrow cells following radiation exposure [11]. Altered gene expression correlates with the loss of clonogenicity of the bone marrow cells following radiation exposure due to either apoptosis and/or accelerated senescence. The proteomic analysis of the bone marrow tissue following radiation exposure provided a different data set of radiation-induced cellular changes compared with the data set provided by gene expression analyses, providing an increased understanding of the cellular and biological impact of radiation on the bone marrow environment. We propose that the identification of the proteins involved will increase our overall understanding of the biological effects of ionizing radiation
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