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

DOI: 10.3390/ijms14023325

Keywords: DNA damage, oxidative stress, comet assay, genotoxicity, apolipoprotein E

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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.

 References

[1]  Ross, R. Atherosclerosis--an inflammatory disease. N. Engl. J. Med 1999, 340, 115–126.
[2]  Vasquez, E.C.; Peotta, V.A.; Gava, A.L.; Pereira, T.M.; Meyrelles, S.S. Cardiac and vascular phenotypes in the apolipoprotein E-deficient mouse. J. Biomed. Sci. 2012, 19, doi:10.1186/1423-0127-19-22.
[3]  Marnett, L.J. Oxyradicals and DNA damage. Carcinogenesis 2003, 21, 361–370.
[4]  Bauer, V.; Sotníková, R.; Drábiková, K. Effects of reactive oxygen species and neutrophils on endothelium-dependent relaxation of rat thoracic aorta. Interdiscip. Toxicol 2011, 4, 191–197.
[5]  McEwen, J.E.; Zimniak, P.; Mehta, J.L.; Shmookler Reis, R.J. Molecular pathology of aging and its implications for senescent coronary atherosclerosis. Curr. Opin. Cardiol 2005, 20, 399–406.
[6]  Madamanchi, N.R.; Runge, M.S. Mitochondrial dysfunction in atherosclerosis. Circ. Res 2007, 100, 460–473.
[7]  Zhang, X.; Qi, R.; Xian, X.; Yang, F.; Blackstein, M.; Deng, X.; Fan, J.; Ross, C.; Karasinska, J.; Hayden, M.R.; et al. Spontaneous atherosclerosis in aged lipoprotein lipase-deficient mice with severe hypertriglyceridemia on a normal chow diet. Circ. Res 2008, 102, 250–256.
[8]  Collins, A.R.; Lyon, C.J.; Xia, X.; Liu, J.Z.; Tangirala, R.K.; Yin, F.; Boyadjian, R.; Bikineyeva, A.; Praticò, D.; Harrison, D.G.; et al. Age-accelerated atherosclerosis correlates with failure to upregulate antioxidant genes. Circ. Res 2009, 104, e42–e54.
[9]  Hasty, P.; Campisi, J.; Hoeijmakers, J.; van Steeg, H.; Vijg, J. Aging and genome maintenance: lessons from the mouse? Science 2003, 299, 1355–1359.
[10]  Kregel, K.C.; Zhang, H.J. An integrated view of oxidative stress in aging: basic mechanisms, functional effects, and pathological considerations. Am. J. Physiol. Regul. Integr. Comp. Physiol 2007, 292, R18–R36.
[11]  Vasquez, E.C.; Peotta, V.A.; Meyrelles, S.S. Cardiovascular autonomic imbalance and baroreflex dysfunction in the apolipoprotein E-deficient mouse. Cell Physiol. Biochem 2012, 29, 635–646.
[12]  Pereira, T.M.; Nogueira, B.V.; Lima, L.C.; Porto, M.L.; Arruda, J.A.; Vasquez, E.C.; Meyrelles, S.S. Cardiac and vascular changes in elderly atherosclerotic mice: The influence of gender. Lipids Health Dis. 2010, 9, 87.
[13]  Porto, M.L.; Lima, L.C.; Pereira, T.M.; Nogueira, B.V.; Tonini, C.L.; Campagnaro, B.P.; Meyrelles, S.S.; Vasquez, E.C. Mononuclear cell therapy attenuates atherosclerosis in apoE KO mice. Lipids Health. Dis 2011, 10, 155.
[14]  Lima, L.C.; Porto, M.L.; Campagnaro, B.P.; Tonini, C.L.; Nogueira, B.V.; Pereira, T.M.; Vasquez, E.C.; Meyrelles, S.S. Mononuclear cell therapy reverts cuff-induced thrombosis in apolipoprotein E-deficient mice. Lipids Health. Dis 2012, 11, 96.
[15]  Meyrelles, S.S.; Peotta, V.A.; Pereira, T.M.; Vasquez, E.C. Endothelial dysfunction in the apolipoprotein E-deficient mouse: insights into the influence of diet, gender and aging. Lipids Health Dis 2011, 10, 211.
[16]  Folkmann, J.K.; Loft, S.; M？ller, P. Oxidatively damaged DNA in aging dyslipidemic apoE？/？ and wild-type mice. Mutagenesis 2007, 22, 105–110.
[17]  Dalboni, S.P.; Campagnaro, B.P.; Tonini, C.L.; Vasquez, E.C.; Meyrelles, S.S. The concurrence of hypercholesterolemia and aging promotes DNA damage in apolipoprotein E-deficient mice. Open J. Blood Dis 2012, 2, 51–55.
[18]  Cuende, N.; Rico, L.; Herrera, C. Bone marrow mononuclear cells for the treatment of ischemic syndromes: medicinal product or cell transplantation? Stem Cells Trans. Med. 2012, 1, 403–408.
[19]  Campagnaro, B.P.; Gava, A.L.; Meyrelles, S.S.; Vasquez, E.C. Cardiac-autonomic imbalance and baroreflex dysfunction in the renovascular angiotensin-dependent hypertensive mouse. Int. J. Hypertens. 2012, 2012, doi:10.1155/2012/968123.
[20]  Nakashima, Y.; Plump, A.S.; Raines, E.W.; Breslow, J.L.; Ross, R. ApoE-deficient mice develop lesions of all phases of atherosclerosis throughout the arterial tree. Arterioscler. Thromb. Vasc. Biol 1994, 14, 133–140.
[21]  Reddick, R.L.; Zhang, S.H.; Maeda, N. Atherosclerosis in mice lacking apo E: evaluation of lesional development and progression. Arterioscler. Thromb. Vasc. Biol 1994, 14, 141–147.
[22]  Zhang, S.H.; Reddick, R.L.; Piedrahita, J.A.; Maeda, N. Spontaneous hypercholesterolemia and arterial lesions in mice lacking apolipoprotein E. Science 1992, 258, 468–471.
[23]  Jawień, J.; Nasta？ek, P.; Korbut, R. Mouse models of experimental atherosclerosis. J. Physiol. Pharmacol 2004, 55, 503–517.
[24]  Goldschmidt-Clermont, P.J. Loss of bone marrow-derived vascular progenitor cells leads to inflammation and atherosclerosis. Am. Heart J 2003, 146, S5–S12.
[25]  Kojda, G.; Harrison, D. Interactions between NO and reactive oxygen species: pathophysiological importance in atherosclerosis, hypertension, diabetes and heart failure. Cardiovasc. Res 1999, 43, 562–571.
[26]  Groemping, Y.; Rittinger, K. Activation and assembly of the NADPH oxidase: A structural perspective. Biochem. J 2005, 386, 401–416.
[27]  Ballinger, S.W. Mitochondrial dysfunction in cardiovascular disease. Free Radic. Biol. Med 2005, 38, 1278–1295.
[28]  Dikalov, S. Crosstalk between mitochondria and NADPH oxidases. Free Radic. Biol. Med 2011, 51, 1289–1301.
[29]  Schr？der, K.; Vecchione, C.; Jung, O.; Schreiber, J.G.; Shiri-Sverdlov, R.; van Gorp, P.J.; Busse, R.; Brandes, R.P. Xanthine oxidase inhibitor tungsten prevents the development of atherosclerosis in ApoE knockout mice fed a Western-type diet. Free Radic. Biol. Med 2006, 41, 1353–1360.
[30]  Takaya, T.; Hirata, K.; Yamashita, T.; Shinohara, M.; Sasaki, N.; Inoue, N.; Yada, T.; Goto, M.; Fukatsu, A.; Hayashi, T.; et al. A specific role for eNOS-derived reactive oxygen species in atherosclerosis progression. Arterioscler. Thromb. Vasc. Biol 2007, 27, 1632–1637.
[31]  Jawien, J.; Gajda, M.; Wo？kow, P.; Zurańska, J.; Olszanecki, R.; Korbut, R. The effect of montelukast on atherogenesis in apoE/LDLR-double knockout mice. J. Physiol. Pharmacol 2008, 59, 633–639.
[32]  Sheehan, A.L.; Carrell, S.; Johnson, B.; Stanic, B.; Banfi, B.; Miller, F.J., Jr. Role for Nox1 NADPH oxidase in atherosclerosis. Atherosclerosis 2011, 216, 321–326.
[33]  Zou, H.; Stoppani, E.; Volonte, D.; Galbiati, F. Caveolin-1, cellular senescence and age-related diseases. Mech. Ageing. Dev 2001, 132, 533–542.
[34]  Law, A.; Gauthier, S.; Quirion, R. Alteration of nitric oxide synthase activity in young and aged apolipoprotein E-deficient mice. Neurobiol. Aging 2003, 24, 187–190.
[35]  Jiang, F.; Jones, G.T.; Dusting, G.J. Failure of antioxidants to protect against angiotensin II-induced aortic rupture in aged apolipoprotein (E)-deficient mice. Br. J. Pharmacol 2007, 152, 880–890.
[36]  Matthews, C.; Gorenne, I.; Scott, S.; Figg, N.; Kirkpatrick, P.; Ritchie, A.; Goddard, M.; Bennett, M. Vascular smooth muscle cells undergo telomere-based senescence in human atherosclerosis: effects of telomerase and oxidative stress. Circ. Res 2006, 99, 156–164.
[37]  Tatarková, Z.; Kuka, S.; Ra？ay, P.; Lehotsky, J.; Dobrota, D.; Mi？tuna, D.; Kaplán, P. Effects of aging on activities of mitochondrial electron transport chain complexes and oxidative damage in rat heart. Physiol. Res 2011, 60, 281–289.
[38]  Wang, J.C.; Bennett, M. Aging and atherosclerosis: mechanisms, functional consequences, and potential therapeutics for cellular senescence. Circ. Res 2012, 111, 245–259.
[39]  Evans, M.D.; Dizdaroglu, M.; Cooke, M.S. Oxidative DNA damage and disease: induction, repair and significance. Mutat. Res 2004, 567, 1–61.
[40]  Ellahue？e, M.F.; Pérez-Alzola, L.P.; Farfán-Urzua, M.; González-Hormazabal, P.; Garay, M.; Olmedo, M.I.; Last, J.A. Preliminary evaluation of DNA damage related with the smoking habit measured by the comet assay in whole blood cells. Cancer Epidemiol. Biomark. Prev 2004, 13, 1223–1229.
[41]  Singh, N.P.; McCoy, M.T.; Tice, R.R.; Schneider, E.L. A simple technique for quantitation of low levels of DNA damage in individual cells. Exp. Cell Res 1988, 175, 184–191.
[42]  Lee, R.F.; Steinert, S. Use of the single cell gel electrophoresis/comet assay for detecting DNA damage in aquatic (marine and freshwater) animals. Mutat. Res 2003, 544, 43–64.
[43]  Yao, Y.; Tian, X.; Liu, X.; Shao, J.; Lv, Y. The p53-mediated apoptosis in hypercholesterolemia-induced renal injury of rats. J. Huazhong. Univ. Sci. Technol. Med. Sci 2005, 25, 408–411.
[44]  Sevin, G.; Yasa, M.; Akcay, D.Y.; Kirkali, G.; Kerry, Z. Different responses of fluvastatin to cholesterol-induced oxidative modifications in rabbits: evidence for preventive effect against DNA damage. Cell Biochem. Funct 2012, 38, 1278–1295.
[45]  Martinet, W.; Knaapen, M.W.; De Meyer, G.R.; Herman, A.G.; Kockx, M.M. Oxidative DNA damage and repair in experimental atherosclerosis are reversed by dietary lipid lowering. Circ. Res 2001, 88, 733–739.
[46]  Ronsein, G.E.; de Oliveira, M.C.; Medeiros, M.H.; Miyamoto, S.; Di Mascio, P. DNA strand breaks and base modifications induced by cholesterol hydroperoxides. Free. Radic. Res 2011, 45, 266–275.
[47]  Polyak, K.; Xia, Y.; Zweier, J.L.; Kinzler, K.W.; Vogelstein, B. A model for p53-induced apoptosis. Nature 1997, 389, 300–305.
[48]  Mercer, J.; Mahmoudi, M.; Bennett, M. DNA damage, p53, apoptosis and vascular disease. Mutat. Res 2007, 621, 75–86.
[49]  Mercer, J.R.; Cheng, K.K.; Figg, N.; Gorenne, I.; Mahmoudi, M.; Griffin, J.; Vidal-Puig, A.; Logan, A.; Murphy, M.P.; Bennett, M. DNA damage links mitochondrial dysfunction to atherosclerosis and the metabolic syndrome. Circ. Res 2010, 107, 1021–1031.
[50]  Yu, E.; Mercer, J.; Bennett, M. Mitochondria in vascular disease. Cardiovasc. Res 2012, 95, 173–182.
[51]  Shaposhnikov, S.; Larsson, C.; Henriksson, S.; Collins, A.; Nilsson, N. Detection of Alu sequences and mtDNA in comets using padlock probes. Mutagenesis 2006, 21, 243–247.
[52]  Harman, D. Aging: a theory based on free radical and radiation chemistry. J. Gerontol 1956, 11, 298–300.
[53]  Clutton, S. The importance of oxidative stress in apoptosis. Br. Med. Bull 1997, 53, 662–668.
[54]  Berlett, B.S.; Stadtman, E.R. Protein oxidation in aging, disease, and oxidative stress. J. Biol. Chem 1997, 272, 20313–20316.
[55]  Slater, T.F. Free radicals and tissue injury: fact and fiction. Br. J. Cancer. Suppl 1987, 8, 5–10.
[56]  Simon, H.U.; Haj-Yehia, A.; Levi-Schaffer, F. Role of reactive oxygen species (ROS) in apoptosis induction. Apoptosis 2000, 5, 415–418.
[57]  Spiteller, G. The relation of lipid peroxidation processes with atherogenesis: A new theory on atherogenesis. Mol. Nutr. Food Res 2005, 49, 999–1013.
[58]  Bayir, H.; Kagan, V.E. Bench-to-bedside review: Mitochondrial injury, oxidative stress and apoptosis--there is nothing more practical than a good theory. Crit. Care 2008, 12, 206.
[59]  Papaharalambus, C.A.; Griendling, K.K. Basic mechanisms of oxidative stress and reactive oxygen species in cardiovascular injury. Trends. Cardiovasc. Med 2007, 17, 48–54.
[60]  Devlin, A.M.; Clark, J.S.; Reid, J.L.; Dominiczak, A.F. DNA synthesis and apoptosis in smooth muscle cells from a model of genetic hypertension. Hypertension 2000, 36, 110–115.
[61]  Rauscher, F.M.; Goldschmidt-Clermont, P.J.; Davis, B.H.; Wang, T.; Gregg, D.; Ramaswami, P.; Pippen, A.M.; Annex, B.H.; Dong, C.; Taylor, D.A. Aging, progenitor cell exhaustion, and atherosclerosis. Circulation 2003, 108, 457–463.
[62]  Thorin-Trescases, N.; Voghel, G.; Gendron, M.E.; Krummen, S.; Farhat, N.; Drouin, A.; Perrault, L.P.; Thorin, E. Pathological aging of the vascular endothelium: are endothelial progenitor cells the sentinels of the cardiovascular system? Can. J. Cardiol 2005, 21, 1019–1024.
[63]  Goldschmidt-Clermont, P.J.; Seo, D.M.; Wang, L.; Beecham, G.W.; Liu, Z.J.; Vazquez-Padron, R.I.; Dong, C.; Hare, J.M.; Kapiloff, M.S.; Bishopric, N.H.; et al. Inflammation, stem cells and atherosclerosis genetics. Curr. Opin. Mol. Ther 2010, 12, 712–723.
[64]  Dauwe, D.F.; Janssens, S.P. Stem cell therapy for the treatment of myocardial infarction. Curr. Pharm. Des 2011, 17, 3328–3340.
[65]  Strauer, B.E.; Steinhoff, G. 10 years of intracoronary and intramyocardial bone marrow stem cell therapy of the heart: from the methodological origin to clinical practice. J. Am. Coll. Cardiol 2011, 58, 1095–1104.
[66]  Feng, Y.; Yang, S.H.; Xiao, B.J.; Xu, W.H.; Ye, S.N.; Xia, T.; Zheng, D.; Liu, X.Z.; Liao, Y.F. Decreased in the number and function of circulation endothelial progenitor cells in patients with avascular necrosis of the femoral head. Bone 2010, 46, 32–40.

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