TY - JOUR
T1 - The Neuroprotective Effects of SIRT1 on NMDA-Induced Excitotoxicity
AU - Yang, Xiaorong
AU - Si, Peipei
AU - Qin, Huaping
AU - Yin, Litian
AU - Yan, Liang Jun
AU - Zhang, Ce
N1 - Funding Information:
This work was supported by the National Natural Science Foundation of China (no. 31000481, no. 31171023, and no. 81601167), the Natural Science Foundation of Shanxi Province, China (no. 2011011040-2), the Fund for Shanxi Key Subjects Construction (FSKSC) and the Students’ Innovation and Entrepreneurship Training Program of Shanxi Province (no. 2015141).
Publisher Copyright:
© 2017 Xiaorong Yang et al.
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85029815832&partnerID=8YFLogxK
U2 - 10.1155/2017/2823454
DO - 10.1155/2017/2823454
M3 - Article
C2 - 29081884
AN - SCOPUS:85029815832
SN - 1942-0900
VL - 2017
JO - Oxidative Medicine and Cellular Longevity
JF - Oxidative Medicine and Cellular Longevity
M1 - 2823454
ER -