title: NAD attenuates oxidative DNA damages induced by amyloid beta-peptide in primary rat cortical neurons.
abstract: One major pathological hallmark of Alzheimer's disease (AD) is accumulation of senile plaques in patients' brains, mainly composed of amyloid beta-peptide (Aβ). 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 Aβ-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 Aβ25-35 and Aβ1-42 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 Aβ25-35. Furthermore, Aβs 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 Aβ, leading ultimately to neuroprotection in primary cortical culture.
authors.affiliation: Institute of Brain Science and Brain Research Center, National Yang-Ming University , Taipei City , Taiwan.
authors.forename: M-F
authors.initials: MF
authors.lastname: Wu
authors.forename: J-H
authors.initials: JH
authors.lastname: Yin
authors.forename: C-S
authors.initials: CS
authors.lastname: Hwang
authors.forename: C-M
authors.initials: CM
authors.lastname: Tang
authors.forename: D-I
authors.initials: DI
authors.lastname: Yang
mesh_terms: D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology*; D004247:DNA / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D004249:DNA Damage; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D009243:NAD / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D017382:Reactive Oxygen Species; C075222:amyloid beta-protein (1-42); C074636:amyloid beta-protein (25-35); D009243:NAD; D004247:DNA
keywords: 8-hydroxy-2´-deoxyguanosine; Alzheimer's disease; DNA oxidation; amyloid-beta; oxidative stress