Oxidatively damaged DNA in aging dyslipidemic ApoE-/- and wild-type mice.
The free radical theory of aging depicts an accumulation of cellular oxidatively damaged DNA. In this study, we investigated this theory in mice with knocked-out apolipoprotein E gene (ApoE(-/-)), which develops atherosclerosis and wild-type counterparts. The level of oxidatively damaged DNA was investigated as strand breaks, endonuclease III- and formamidopyrimidine DNA glycosylase-sensitive sites by the comet assay. The level of DNA damage was mainly increased with age in the liver of ApoE(-/-) mice, whereas no increase was observed in the aorta or lung of the mice. This suggests that the accumulation of oxidized DNA in the liver of dyslipidemic ApoE(-/-) mice could be secondary to dysfunction of the lipid metabolism. Visually, the aortas of the ApoE(-/-) mice were clearly atherosclerotic as indicated by rigid texture and yellowish in color. However, the unaltered levels of oxidized DNA in severely atherosclerotic aortas of old ( approximately 70 weeks) ApoE(-/-) mice indicate that oxidative stress may not be a generalized phenomenon, but rather related locally to the individual plaques. In conclusion, the results of this study suggest that dyslipidemic ApoE(-/-) mice suffer from hepatic oxidative stress in terms of oxidized DNA, and this effect could be due to the dysfunction of lipid metabolism.
Folkmann
Janne Kjaersgaard
JK
Department of Occupational and Environmental Health, Institute of Public Health, University of Copenhagen, Øster Farimagsgade 5, building 5, 2nd floor, 1014 Copenhagen K, Denmark.
Loft
Steffen
S
Møller
Peter
P
D000375:Aging / Q000235:genetics*; D000818:Animals; D001011:Aorta / Q000378:metabolism; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics*; D004249:DNA Damage; D045647:DNA Glycosylases / Q000378:metabolism; D050171:Dyslipidemias / Q000235:genetics*; D004720:Endonucleases / Q000378:metabolism; D005260:Female; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress
D001057:Apolipoproteins E; D004720:Endonucleases; D045647:DNA Glycosylases