Attenuation of age-dependent oxidative damage to DNA and protein in brainstem of Tg Cu/Zn SOD mice

• Published in: Neurobiology of aging 1998-07, Vol.19 (4), p.311-316
• Main Authors: Cardozo-Pelaez, F., Song, S., Parthasarathy, A., Epstein, C.J., Sanchez-Ramos, J.
• Format: Article
• Language: English
• Subjects: 8-Hydroxy-2′-deoxyguanosine; Aging; Aging - physiology; Animals; Biological and medical sciences; Brain Stem - enzymology; Brain Stem - physiology; Deoxyguanosine - analogs & derivatives; Deoxyguanosine - metabolism; Development. Senescence. Regeneration. Transplantation; DNA Damage - physiology; Free Radicals; Fundamental and applied biological sciences. Psychology; Humans; Mice; Mice, Transgenic; Neostriatum - metabolism; Nerve Tissue Proteins - physiology; Oxidation-Reduction; Oxidative DNA damage; Parkinson’s disease; Protein oxidation; Regression Analysis; Superoxide dismutase; Superoxide Dismutase - genetics; Superoxide Dismutase - physiology; Transgenic mice; Vertebrates: nervous system and sense organs
• ISSN: 0197-4580; 1558-1497
• DOI: 10.1016/S0197-4580(98)00067-0

Age-dependent accumulation of oxidative DNA and protein damage in brainstem and striatum was assessed in normal and transgenic (tg) mice which overexpress human Cu/Zn superoxide dismutase (h-SOD1). A marker of oxidative DNA damage, 8-hydroxy-2′-deoxyguanosine (oxo 8dG), was measured at 3, 12, and 18 months of age in control and tg mice. Cu/Zn SOD, but not MnSOD, activities in brainstems and striata from tg mice were increased compared to controls at all ages. At 18 months, oxo 8dG levels were increased by 58% in brainstem and by 21% in striatum of control mice. In the tg mice, brainstem and striatal oxo 8dG levels were increased to a lesser extent than in the corresponding controls. Protein oxidation (carbonyl content), was increased by 59% at 18 months in control brainstem, but not in striatum, and the increase was significantly attenuated in the tg mice. In summary, oxidative damage to DNA and protein increased with age in brainstem (and to a lesser extent in striatum), and augmented Cu/Zn SOD activity modified the extent of DNA and protein damage.