The Neuroprotective Effects of SIRT1 on NMDA-Induced Excitotoxicity

Xiaorong Yang, Peipei Si, Huaping Qin, Litian Yin, Liang-Jun Yan, Ce Zhang

Research output: Contribution to journalArticleResearchpeer-review

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Abstract

Silent information regulator 1 (SIRT1), an NAD+-dependent deacetylase, is involved in the regulation of gene transcription, energy metabolism, and cellular aging and has become an important therapeutic target across a range of diseases. Recent research has demonstrated that SIRT1 possesses neuroprotective effects; however, it is unknown whether it protects neurons from NMDA-mediated neurotoxicity. In the present study, by activation of SIRT1 using resveratrol (RSV) in cultured cortical neurons or by overexpression of SIRT1 in SH-SY5Y cell, we aimed to evaluate the roles of SIRT1 in NMDA-induced excitotoxicity. Our results showed that RSV or overexpression of SIRT1 elicited inhibitory effects on NMDA-induced excitotoxicity including a decrease in cell viability, an increase in lactate dehydrogenase (LDH) release, and a decrease in the number of living cells as measured by CCK-8 assay, LDH test, and Calcein-AM and PI double staining. RSV or overexpression of SIRT1 significantly improved SIRT1 deacetylase activity in the excitotoxicity model. Further study suggests that overexpression of SIRT1 partly suppressed an NMDA-induced increase in p53 acetylation. These results indicate that SIRT1 activation by either RSV or overexpression of SIRT1 can exert neuroprotective effects partly by inhibiting p53 acetylation in NMDA-induced neurotoxicity.

Original languageEnglish
Article number2823454
JournalOxidative Medicine and Cellular Longevity
Volume2017
DOIs
StatePublished - 1 Jan 2017

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Neuroprotective Agents
N-Methylaspartate
Acetylation
L-Lactate Dehydrogenase
Neurons
Chemical activation
Cells
Sincalide
Cell Aging
Transcription
NAD
Energy Metabolism
Assays
Cell Survival
Cell Count
Genes
Aging of materials
Staining and Labeling
resveratrol
Research

Cite this

Yang, Xiaorong ; Si, Peipei ; Qin, Huaping ; Yin, Litian ; Yan, Liang-Jun ; Zhang, Ce. / The Neuroprotective Effects of SIRT1 on NMDA-Induced Excitotoxicity. In: Oxidative Medicine and Cellular Longevity. 2017 ; Vol. 2017.
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abstract = "Silent information regulator 1 (SIRT1), an NAD+-dependent deacetylase, is involved in the regulation of gene transcription, energy metabolism, and cellular aging and has become an important therapeutic target across a range of diseases. Recent research has demonstrated that SIRT1 possesses neuroprotective effects; however, it is unknown whether it protects neurons from NMDA-mediated neurotoxicity. In the present study, by activation of SIRT1 using resveratrol (RSV) in cultured cortical neurons or by overexpression of SIRT1 in SH-SY5Y cell, we aimed to evaluate the roles of SIRT1 in NMDA-induced excitotoxicity. Our results showed that RSV or overexpression of SIRT1 elicited inhibitory effects on NMDA-induced excitotoxicity including a decrease in cell viability, an increase in lactate dehydrogenase (LDH) release, and a decrease in the number of living cells as measured by CCK-8 assay, LDH test, and Calcein-AM and PI double staining. RSV or overexpression of SIRT1 significantly improved SIRT1 deacetylase activity in the excitotoxicity model. Further study suggests that overexpression of SIRT1 partly suppressed an NMDA-induced increase in p53 acetylation. These results indicate that SIRT1 activation by either RSV or overexpression of SIRT1 can exert neuroprotective effects partly by inhibiting p53 acetylation in NMDA-induced neurotoxicity.",
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The Neuroprotective Effects of SIRT1 on NMDA-Induced Excitotoxicity. / Yang, Xiaorong; Si, Peipei; Qin, Huaping; Yin, Litian; Yan, Liang-Jun; Zhang, Ce.

In: Oxidative Medicine and Cellular Longevity, Vol. 2017, 2823454, 01.01.2017.

Research output: Contribution to journalArticleResearchpeer-review

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