Exposure to lead and the developmental origin of oxidative DNA damage in the aging brain.
نویسندگان
چکیده
Oxidative damage to DNA has been associated with neurodegenerative diseases. Developmental exposure to lead (Pb) has been shown to elevate the Alzheimer's disease (AD) related beta-amyloid peptide (Abeta), which is known to generate reactive oxygen species in the aging brain. This study measures the lifetime cerebral 8-hydroxy-2'-deoxyguanosine (oxo8dG) levels and the activity of the DNA repair enzyme 8-oxoguanine DNA glycosylase (Ogg1) in rats developmentally exposed to Pb. Oxo8dG was transiently modulated early in life (Postnatal day 5), but was later elevated 20 months after exposure to Pb had ceased, while Ogg1 activity was not altered. Furthermore, an age-dependent loss in the inverse correlation between Ogg1 activity and oxo8dG accumulation was observed. The effect of Pb on oxo8dG levels did not occur if animals were exposed to Pb in old age. These increases in DNA damage occurred in the absence of any Pb-induced changes in copper/zinc-superoxide dismutase (SOD1), manganese-SOD (SOD2), and reduced-form glutathion (GSH). These data suggest that oxidative damage and neurodegeneration in the aging brain could be impacted by the developmental disturbances.
منابع مشابه
Role of Propolis on Oxidative Stress in Fish Brain
Introduction: Cypermethrin causes its neurotoxic effect through voltage-dependent sodium channels and integral protein ATPases in the neuronal membrane. Brain and nerve damage are often associated with low residual level of pesticides. In vitro and in vivo studies have also shown that pesticides cause free radical-mediated tissue damage in brain. Propolis has antioxidant properties. The main ch...
متن کاملEvaluation of Oxidative Stress and DNA Damage Indicators Following A Long Period of Resistance Training in Sedentary Older Men
Background and Aim: Excessive production of free radicals and the accumulation of oxidative damages play an important role in accelerating the aging process. However, one of the ways to fight against aging and related diseases is through physical activity. The aim of the present study was to investigate the effect of 12 weeks of resistance training on oxidative stress indicators (8-iso-prostagl...
متن کاملEffect of Exposure to Ionizing Radiation on Biomarker of Oxidative Damage of DNA
Introduction: one of the most important complications of exposure to ionizing radiation is emergence of cancer tumors, which happens as a result of oxidative DNA. Therefore, the present study was conducted, aimed to measuring 8-DIHYDROxy- 2’- DEOXYGUANOSINE (8-OHdG) level in radiographers’ urine as oxidative damage biomarker, as well as comparing this biomarker with cumulative effective doses....
متن کاملOGG1 DNA Repair Gene Polymorphism As a Biomarker of Oxidative and Genotoxic DNA Damage
Background: Single nucleotide polymorphisms in 8-oxoguanine DNA glycosylase-1 (OGG1) gene modulates DNA repair capacity and functions as one of the first lines of protective mechanisms against 8-hydroxy-2’-deoxyguanosine (8-OHdG) mutagenicity. OGG1-Cys326 gene polymorphism may decrease DNA repair function, causing oxidative stress due to higher oxidative DNA damage. The main purpose of this stu...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- FASEB journal : official publication of the Federation of American Societies for Experimental Biology
دوره 20 6 شماره
صفحات -
تاریخ انتشار 2006