Expression of Ogg1 and detection of 8-oxoG DNA glycosylase activity in neural progenitors

ABSTRACT Normal cellular metabolism generates reactive oxygen species which interact with DNA, lipids and proteins in cells. Cellular damage due to oxidative stress is proposed to contribute to the pathophysiology of cancer, neurodegenerative diseases including Alzheimer s and Parkinson s and to the process of aging. The central nervous system is thought to be particularly susceptible to oxidative stress due to the high rate of oxygen consumption. Base excision DNA repair (BER) is the major pathway that removes oxidative DNA base lesions. Among hundreds of lesions, 7,8-dihydro-8-oxoguanine (8-oxoG) is believed to be one of the most important oxidized lesions due to their relatively high incidence and their miscoding properties.OGG1 (8-oxoguanine DNA glycosylase-1) is one of the main DNA glycosylases present in mammalian cells that removes 7,8-dihydro-8-oxoguanine (8-oxoG) lesions. In this study we have investigated 8-oxoG repair capacity of neurospheres derived from newborn and adult mice. We show that Ogg1 is the major glycosylase initiating 8-oxoG repair. Moreover 8-oxoG activity decrases with age and upon cell differentiation