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Nature’s Timepiece—Molecular Coordination of Metabolism and Its Impact on Aging
Int. J. Mol. Sci. 2013, 14(2), 3325-3342; doi:10.3390/ijms14023325
Article

Effects of Aging and Hypercholesterolemia on Oxidative Stress and DNA Damage in Bone Marrow Mononuclear Cells in Apolipoprotein E-deficient Mice

1,†
,
1,†
,
1,†
,
2,3,†
,
1,4,†
 and
1,*
1 Laboratory of Transgenes, Health Sciences Center, Federal University of Espirito Santo, Vitoria, ES 29043-900, Brazil 2 Federal Institute of Education, Science and Technology (IFES), Vila Velha, ES 29106-010, Brazil 3 Department of Pharmaceutical Sciences, University of Vila Velha (UVV), Vila Velha, ES 29102-770, Brazil 4 Emescam School of Health Sciences, Vitoria, ES 29045-402, Brazil These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 26 November 2012 / Revised: 10 January 2013 / Accepted: 29 January 2013 / Published: 5 February 2013
(This article belongs to the Special Issue Oxidative Stress and Ageing)
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Abstract

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.
Keywords: DNA damage; oxidative stress; comet assay; genotoxicity; apolipoprotein E DNA damage; oxidative stress; comet assay; genotoxicity; apolipoprotein E
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Tonini, C.L.; Campagnaro, B.P.; Louro, L.P.S.; Pereira, T.M.C.; Vasquez, E.C.; Meyrelles, S.S. Effects of Aging and Hypercholesterolemia on Oxidative Stress and DNA Damage in Bone Marrow Mononuclear Cells in Apolipoprotein E-deficient Mice. Int. J. Mol. Sci. 2013, 14, 3325-3342.

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