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NAD+ Induces Autophagy of Neuro2a Cells by Increasing Oxidative Stress
Author(s) -
Han Jin,
Shi Shengtao,
Shao Jiaxiang,
Xia Weiliang,
Ying Weihai
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1004.3
Subject(s) - nad+ kinase , autophagy , oxidative stress , nicotinamide , programmed cell death , microbiology and biotechnology , chemistry , neuroprotection , cell , biochemistry , biology , apoptosis , enzyme , pharmacology
NAD + plays important roles in various biological processes. Previous studies have shown that NAD + treatment can significantly decrease genotoxic agent‐induced death of primary neurons and astrocytes, and NAD + administration can markedly reduce ischemic brain damage in rodents. However, whether NAD + treatment affects cell autophagy remains unknown. In this study we have found that treatment of NAD + at concentrations from 100 μM to 10 mM can induce autophagy of Neuro2a cells, as assessed by the immunoblotting of LC 3 I/II conversion,, real‐time qPCR quantification of beclin‐1 expression, and monodansylcadaverine (MDC) staining. Our study has also indicated that oxidative stress mediates the effects of NAD + on the autophagy of the cells: NAD + induced increases in the superoxide levels in Neuro2a cells, and treatment of the cells with antioxidants attenuated the effects of NAD + on the autophagy. We have further indicated the NAD + ‐induced autophagy contributes to the NAD + ‐induced decrease in the survival of the cells. Our experimental results have also argued against the possibility that NAD + affects the autophagy through its degradation product ‐‐‐ nicotinamide. In summary, our study has provided the first evidence that NAD + treatment can induce autophagy of such tumor cells as Neuro2a by generating oxidative stress, which contributes to the NAD + ‐induced decrease in cell survival (Supported by a Key Research Grant of Shanghai Municipal Scientific Committee #08JC1415400, a National Key Basic Research ‘973 Program Grant’ #2010CB834306, a Shanghai Engineering Center Grant of Equipment and Technology of Physical Therapy for Major Diseases #08DZ2211200).