Laboratory of Transgenes, Health Sciences Center, Federal University of Espirito Santo, Vitoria, ES 29043-900, Brazil.
Int J Mol Sci. 2013 Feb 5;14(2):3325-42. doi: 10.3390/ijms14023325.
Recent evidence from apolipoprotein E-deficient (apoE-/-) mice shows that aging and atherosclerosis are closely associated with increased oxidative stress and DNA damage in some cells and tissues. However, bone marrow cells, which are physiologically involved in tissue repair have not yet been investigated. In the present study, we evaluated the influence of aging and hypercholesterolemia on oxidative stress, DNA damage and apoptosis in bone marrow cells from young and aged apoE-/- mice compared with age-matched wild-type C57BL/6 (C57) mice, using the comet assay and flow cytometry. The production of both superoxide and hydrogen peroxide in bone marrow cells was higher in young apoE-/- mice than in age-matched C57 mice, and reactive oxygen species were increased in aged C57 and apoE-/- mice. Similar results were observed when we analyzed the DNA damage and apoptosis. Our data showed that both aging and hypercholesterolemia induce the increased production of oxidative stress and consequently DNA damage and apoptosis in bone marrow cells. This study is the first to demonstrate a functionality decrease of the bone marrow, which is a fundamental extra-arterial source of the cells involved in vascular injury repair.
最近，载脂蛋白 E 缺陷（apoE-/-）小鼠的研究证据表明，衰老和动脉粥样硬化与某些细胞和组织中氧化应激和 DNA 损伤的增加密切相关。然而，生理上参与组织修复的骨髓细胞尚未得到研究。在本研究中，我们使用彗星试验和流式细胞术，评估了衰老和高胆固醇血症对年轻和年老 apoE-/-小鼠与年龄匹配的野生型 C57BL/6（C57）小鼠骨髓细胞中氧化应激、DNA 损伤和细胞凋亡的影响。与年龄匹配的 C57 小鼠相比，年轻 apoE-/-小鼠的骨髓细胞中超氧化物和过氧化氢的产生更高，而在年老的 C57 和 apoE-/-小鼠中，活性氧增加。当我们分析 DNA 损伤和细胞凋亡时，也观察到了类似的结果。我们的数据表明，衰老和高胆固醇血症都会导致骨髓细胞中氧化应激的产生增加，进而导致 DNA 损伤和细胞凋亡。这项研究首次证明了骨髓功能下降，骨髓是参与血管损伤修复的细胞的一个重要的非动脉来源。
