title: Exogenous NAD(+) decreases oxidative stress and protects H2O2-treated RPE cells against necrotic death through the up-regulation of autophagy.
abstract: Increased oxidative stress, which can lead to the retinal pigment epithelium (RPE) cell death by inducing ATP depletion and DNA repair, is believed to be a prominent pathology in age-related macular degeneration (AMD). In the present study, we showed that and 0.1 mM nicotinamide adenine dinucleotide (NAD(+)) administration significantly blocked RPE cell death induced by 300 μM H2O2. Further investigation showed that H2O2 resulted in increased intracellular ROS level, activation of PARP-1 and subsequently necrotic death of RPE cells. Exogenous NAD(+) administration significantly decreased intracellular and intranuclear ROS levels in H2O2-treated RPE cells. In addition, NAD(+) administration to H2O2-treated RPE cells inhibited the activation of PARP-1 and protected the RPE cells against necrotic death. Moreover, exogenous NAD(+) administration up-regulated autophagy in the H2O2-treated RPE cells. Inhibition of autophagy by LY294002 blocked the decrease of intracellular and intranuclear ROS level. Besides, inhibition of autophagy by LY294002 abolished the protection of exogenous NAD(+) against H2O2-induced cell necrotic death. Taken together, our findings indicate that that exogenous NAD(+) administration suppresses H2O2-induced oxidative stress and protects RPE cells against PARP-1 mediated necrotic death through the up-regulation of autophagy. The results suggest that exogenous NAD(+) administration might be potential value for the treatment of AMD.
authors.affiliation: Department of Ophthalmology, Xinhua Hospital, Shanghai Jiaotong University Scool of Medicine, Shanghai, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Ophthalmology, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Ke-Ke
authors.initials: KK
authors.lastname: Zhao
authors.affiliation: Department of Ophthalmology, Xinhua Hospital, Shanghai Jiaotong University Scool of Medicine, Shanghai, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Tong
authors.affiliation: Department of Ophthalmology, Xinhua Hospital, Shanghai Jiaotong University Scool of Medicine, Shanghai, China.
authors.forename: Ya-Li
authors.initials: YL
authors.lastname: Zhou
authors.affiliation: Department of Ophthalmology, Xinhua Hospital, Shanghai Jiaotong University Scool of Medicine, Shanghai, China.
authors.forename: Yi-Xiao
authors.initials: YX
authors.lastname: Wang
authors.affiliation: Department of Ophthalmology, Xinhua Hospital, Shanghai Jiaotong University Scool of Medicine, Shanghai, China.
authors.forename: Pei-Quan
authors.initials: PQ
authors.lastname: Zhao
authors.affiliation: Department of Ophthalmology, Xinhua Hospital, Shanghai Jiaotong University Scool of Medicine, Shanghai, China.
authors.forename: Zhao-Yang
authors.initials: ZY
authors.lastname: Wang
mesh_terms: D001343:Autophagy / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D008268:Macular Degeneration / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008954:Models, Biological; D009025:Morpholines / Q000494:pharmacology; D009243:NAD / Q000378:metabolism* / Q000494:pharmacology; D009336:Necrosis; D016877:Oxidants / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects; D000071137:Poly (ADP-Ribose) Polymerase-1 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D015854:Up-Regulation
chemical_list: D002867:Chromones; D009025:Morpholines; D016877:Oxidants; D017382:Reactive Oxygen Species; D009243:NAD; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D006861:Hydrogen Peroxide; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1