Journal
FREE RADICAL RESEARCH
Volume 48, Issue 7, Pages 794-805Publisher
INFORMA HEALTHCARE
DOI: 10.3109/10715762.2014.907889
Keywords
8-hydroxy-2 '-deoxyguanosine; Alzheimer's disease; amyloid-beta; DNA oxidation; oxidative stress
Categories
Funding
- National Science Council in Taiwan [NSC 98-2314-B-010-020-MY3, NSC 101-2314-B-010-042MY2]
- Ministry of Education in Taiwan-Aim for the Top University Plan [102AC-B5]
- Cheng Hsin General Hospital [102F218C12]
- Department of Health in Taipei City Government [10201-62-067]
- Yen Tjing Ling Medical Foundation [CI-97-4]
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One major pathological hallmark of Alzheimer's disease (AD) is accumulation of senile plaques in patients' brains, mainly composed of amyloid beta-peptide (A beta). Nicotinamide adenine dinucleotide (NAD) has emerged as a common mediator regulating energy metabolism, mitochondrial function, aging, and cell death, all of which are critically involved in neuronal demise observed in AD. In this work, we tested the hypothesis that NAD may attenuate A beta-induced DNA damages, thereby conferring neuronal resistance to primary rat cortical cultures. We found that co-incubation of NAD dose-dependently attenuated neurotoxicity mediated by A beta 25-35 and A beta 1-42 in cultured rat cortical neurons, with the optimal protective dosage at 50 mM. NAD also abolished the formation of reactive oxygen species (ROS) induced by A beta 25-35. Furthermore, A beta s were capable of inducing oxidative DNA damages by increasing the extents of 8-hydroxy-2'-deoxyguanosine (8-OH-dG), numbers of apurinic/apyrimidinic (AP) sites, genomic DNA single-stranded breaks (SSBs), as well as DNA double-stranded breaks (DSBs)/fragmentation, which can all be attenuated upon co-incubation with NAD. Our results thus reveal a novel finding that NAD is protective against DNA damage induced by existing A beta, leading ultimately to neuroprotection in primary cortical culture.
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