Resveratrol inhibits β-amyloid-induced neuronal apoptosis via regulation of p53 acetylation in PC12 cells

Ai,Zhibing; Li,Chengyan; Li,Longti; He,Guohou

doi:10.3892/mmr.2014.3034

Resveratrol inhibits β-amyloid-induced neuronal apoptosis via regulation of p53 acetylation in PC12 cells

Authors:
- Zhibing Ai
- Chengyan Li
- Longti Li
- Guohou He
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Affiliations: Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China, Department of Neurology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China
Published online on: December 3, 2014 https://doi.org/10.3892/mmr.2014.3034
Pages: 2429-2434
Copyright: © Ai et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

The natural product resveratrol possesses diverse biological activities, including anti‑inflammatory, anti‑oxidant, anti‑cancer and anti‑aging effects in multiple organisms. The neuroprotective role of resveratrol has recently been reported in a cell model of amyloid (A)β(25‑35)‑induced neurotoxic injury using PC12 cells. However, the pathomechanism by which resveratrol inhibits neuronal apoptosis has remained to be elucidated. The present study therefore aimed to confirm the neuroprotective effects of resveratrol in an Aβ(25‑35)‑induced model of neurotoxicity in PC12 cells and elucidate the mechanisms underlying these effects. It was demonstrated that resveratrol exerted neuronal protection through inhibition of cell apoptosis, which was associated with an increased acetylation level of p53. In accordance with this effect, when the acetylation level of p53 was decreased by p53 acetylation inhibitor pifithrin‑α, the protective effects of resveratrol were abrogated. In conclusion, it was revealed that resveratrol inhibited Aβ(25‑35)‑induced cell apoptosis via the acetylation of p53 in PC12 cells.

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1	Hosseinimehr SJ and Hosseini SA: Resveratrol sensitizes selectively thyroid cancer cell to 131-iodine toxicity. J Toxicol. 2014:8395972014. View Article : Google Scholar : PubMed/NCBI
2	Witte AV, Kerti L, Margulies DS and Flöel A: Effects of resveratrol on memory performance, hippocampal functional connectivity, and glucose metabolism in healthy older adults. J Neurosci. 34:7862–7870. 2014. View Article : Google Scholar : PubMed/NCBI
3	Pervaiz S: Resveratrol: from grapevines to mammalian biology. FASEB J. 17:1975–1985. 2003. View Article : Google Scholar : PubMed/NCBI
4	Wang J, Ho L, Zhao W, et al: Grape-derived polyphenolics prevent Abeta oligomerization and attenuate cognitive deterioration in a mouse model of Alzheimer’s disease. J Neurosci. 28:6388–6392. 2008. View Article : Google Scholar : PubMed/NCBI
5	Scalbert A, Manach C, Morand C, Rémésy C and Jiménez L: Dietary polyphenols and the prevention of diseases. Crit Rev Food Sci Nutr. 45:287–306. 2005. View Article : Google Scholar : PubMed/NCBI
6	Tomayko EJ, Cachia AJ, Chung HR and Wilund KR: Resveratrol supplementation reduces aortic atherosclerosis and calcification and attenuates loss of aerobic capacity in a mouse model of uremia. J Med Food. 17:278–283. 2014. View Article : Google Scholar : PubMed/NCBI
7	Liu T, Zang N, Zhou N, et al: Resveratrol inhibits the TRIF-dependent pathway by upregulating sterile alpha and armadillo motif protein, contributing to anti-inflammatory effects after respiratory syncytial virus infection. J Virol. 88:4229–4236. 2014. View Article : Google Scholar : PubMed/NCBI
8	Andrade JM, Frade AC, Guimarães JB, et al: Resveratrol increases brown adipose tissue thermogenesis markers by increasing SIRT1 and energy expenditure and decreasing fat accumulation in adipose tissue of mice fed a standard diet. Eur J Nutr. 53:1503–1510. 2014. View Article : Google Scholar : PubMed/NCBI
9	Pasinetti GM, Wang J, Marambaud P, et al: Neuroprotective and metabolic effects of resveratrol: therapeutic implications for Huntington’s disease and other neurodegenerative disorders. Exp Neurol. 232:1–6. 2011. View Article : Google Scholar : PubMed/NCBI
10	Bournival J, Quessy P and Martinoli MG: Protective effects of resveratrol and quercetin against MPP+ -induced oxidative stress act by modulating markers of apoptotic death in dopaminergic neurons. Cell Mol Neurobiol. 29:1169–1180. 2009. View Article : Google Scholar : PubMed/NCBI
11	Huang TC, Lu KT, Wo YY, Wu YJ and Yang YL: Resveratrol protects rats from Aβ-induced neurotoxicity by the reduction of iNOS expression and lipid peroxidation. PLoS One. 6:e291022011. View Article : Google Scholar
12	Feng X, Liang N, Zhu D, et al: Resveratrol inhibits β-amyloid-induced neuronal apoptosis through regulation of SIRT1-ROCK1 signaling pathway. PLoS One. 8:e598882013. View Article : Google Scholar
13	Sharma M and Gupta YK: Chronic treatment with trans resveratrol prevents intracerebroventricular streptozotocin induced cognitive impairment and oxidative stress in rats. Life Sci. 71:2489–2498. 2002. View Article : Google Scholar : PubMed/NCBI
14	Luo J, Nikolaev AY, Imai S, et al: Negative control of p53 by Sir2alpha promotes cell survival under stress. Cell. 107:137–148. 2001. View Article : Google Scholar : PubMed/NCBI
15	Vaziri H, Dessain SK, Ng Eaton E, et al: hSIR2(SIRT1) functions as an NAD-dependent p53 deacetylase. Cell. 107:149–159. 2001. View Article : Google Scholar : PubMed/NCBI
16	Mihara M, Erster S, Zaika A, et al: p53 has a direct apoptogenic role at the mitochondria. Mol Cell. 11:577–590. 2003. View Article : Google Scholar : PubMed/NCBI
17	Brooks CL and Gu W: Ubiquitination, phosphorylation and acetylation: the molecular basis for p53 regulation. Curr Opin Cell Biol. 15:164–171. 2003. View Article : Google Scholar : PubMed/NCBI
18	Luo J, Li M, Tang Y, Laszkowska M, Roeder RG and Gu W: Acetylation of p53 augments its site-specific DNA binding both in vitro and in vivo. Proc Natl Acad Sci USA. 101:2259–2264. 2004. View Article : Google Scholar : PubMed/NCBI
19	Appella E and Anderson CW: Post-translational modifications and activation of p53 by genotoxic stresses. Eur J Biochem. 268:2764–2772. 2001. View Article : Google Scholar
20	Walsh DM and Selkoe DJ: A beta oligomers - a decade of discovery. J Neurochem. 101:1172–1184. 2007. View Article : Google Scholar : PubMed/NCBI
21	Jia LQ, Yang GL, Ren L, et al: Tanshinone IIA reduces apoptosis induced by hydrogen peroxide in the human endothelium-derived EA.hy926 cells. J Ethnopharmacol. 143:100–108. 2012. View Article : Google Scholar : PubMed/NCBI
22	Yang Y, Chen S, Zhang J, Li C, Sun Y, Zhang L and Zheng X: Stimulation of autophagy prevents amyloid-β peptide-induced neuritic degeneration in PC12 cells. J Alzheimers Dis. 40:929–939. 2014.
23	Liao Y and Hung MC: Physiological regulation of Akt activity and stability. Am J Transl Res. 2:19–42. 2010.PubMed/NCBI
24	Komarov PG, Komarova EA, Kondratov RV, et al: A chemical inhibitor of p53 that protects mice from the side effects of cancer therapy. Science. 285:1733–1737. 1999. View Article : Google Scholar : PubMed/NCBI
25	Athar M, Back JH, Kopelovich L, Bickers DR and Kim AL: Multiple molecular targets of resveratrol: Anti-carcinogenic mechanisms. Arch Biochem Biophys. 486:95–102. 2009. View Article : Google Scholar : PubMed/NCBI
26	Voellger B, Kirches E, Wilisch-Neumann A, et al: Resveratrol decreases B-cell lymphoma-2 expression and viability in GH3 pituitary adenoma cells of the rat. Onco Targets Ther. 9:1269–1276. 2013. View Article : Google Scholar : PubMed/NCBI
27	Akhter R, Sanphui P and Biswas SC: The essential role of p53-up-regulated modulator of apoptosis (Puma) and its regulation by FoxO3a transcription factor in β-amyloid-induced neuron death. J Biol Chem. 289:10812–10822. 2014. View Article : Google Scholar : PubMed/NCBI
28	Renaud J, Bournival J, Zottig X and Martinoli MG: Resveratrol protects DAergic PC12 cells from high glucose-induced oxidative stress and apoptosis: effect on p53 and GRP75 localization. Neurotox Res. 25:110–123. 2014. View Article : Google Scholar :
29	Guarente L: Sir2 links chromatin silencing, metabolism, and aging. Genes Dev. 14:1021–1026. 2000.PubMed/NCBI
30	Lamming DW, Wood JG and Sinclair DA: Small molecules that regulate lifespan: evidence for xenohormesis. Mol Microbiol. 53:1003–1009. 2004. View Article : Google Scholar : PubMed/NCBI
31	Lhee SJ, Song EK, Kim YR and Han MK: SIRT1 inhibits p53 but not NF-κB transcriptional activity during differentiation of mouse embryonic stem cells into embryoid bodies. Int J Stem Cells. 5:125–129. 2012. View Article : Google Scholar
32	Hori YS, Kuno A, Hosoda R and Horio Y: Regulation of FOXOs and p53 by SIRT1 modulators under oxidative stress. PLoS One. 8:e738752013. View Article : Google Scholar : PubMed/NCBI