Salidroside protects PC12 cells from Aβ1‑40‑induced cytotoxicity by regulating the nicotinamide phosphoribosyltransferase signaling pathway

Huang,Xujiao; Xing,Sanli; Chen,Chuan; Yu,Zhihua; Chen,Jiulin

doi:10.3892/mmr.2017.6931

Salidroside protects PC12 cells from Aβ1‑40‑induced cytotoxicity by regulating the nicotinamide phosphoribosyltransferase signaling pathway

Authors:
- Xujiao Huang
- Sanli Xing
- Chuan Chen
- Zhihua Yu
- Jiulin Chen
View Affiliations

Affiliations: Geriatrics Laboratory, Shanghai Geriatric Institute of Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200031, P.R. China
Published online on: July 5, 2017 https://doi.org/10.3892/mmr.2017.6931
Pages: 2700-2706
Copyright: © Huang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Alzheimer's disease (AD) is the most common type of senile dementia, which often develops in elderly or presenile individuals. As one of the pathological features of AD, amyloid β‑protein (Aβ) causes energy dysmetabolism, thereby inducing cellular damage and apoptosis. Salidroside is the main active component of the traditional Chinese medicine Rhodiola. Previous studies have demonstrated that salidroside exerts a regulatory role in energy metabolism. However, the role and the mechanism of action of salidroside in AD remain unclear. Therefore, the present study used Aβ1‑40 to induce damage in PC12 cells, thereby establishing a cell model of AD. In addition, salidroside treatment was performed to investigate the protective effect of salidroside and the underlying mechanisms. Aβ1‑40‑induced neuronal toxicity reduced cell viability and caused cellular damage. As a result, the expression level of nicotinamide phosphoribosyltransferase (NAMPT) decreased, the synthesis of nicotinamide adenine dinucleotide (NAD+; an energy metabolism‑associated coenzyme) became insufficient, and the NAD+/nicotinamide adenine dinucleotide hydride ratio was reduced. Administration of salidroside alleviated Aβ‑induced cell damage and increased the expression level of the key protein NAMPT and the synthesis of NAD+. The results of the present study demonstrate that salidroside exerts a protective effect on Aβ1‑40‑damaged PC12 cells. The underlying mechanism may be associated with the regulation of energy metabolism that relies predominantly on the NAMPT signaling pathway.

View Figures

View References

1	Van Cauwenberghe C, Van Broeckhoven C and Sleegers K: The genetic landscape of Alzheimer disease: Clinical implications and perspectives. Genet Med. 18:421–430. 2016. View Article : Google Scholar : PubMed/NCBI
2	Scheltens P, Blennow K, Breteler MM, de Strooper B, Frisoni GB, Salloway S and Van der Flier WM: Alzheimer's disease. Lancet. 388:505–517. 2016. View Article : Google Scholar : PubMed/NCBI
3	Perl DP: Neuropathology of Alzheimer's disease. Mt Sinai J Med. 77:32–42. 2010. View Article : Google Scholar : PubMed/NCBI
4	Serrano-Pozo A, Frosch MP, Masliah E and Hyman BT: Neuropathological alterations in Alzheimer disease. Cold Spring Harb Perspect Med. 1:a0061892011. View Article : Google Scholar : PubMed/NCBI
5	Sadigh-Eteghad S, Sabermarouf B, Majdi A, Talebi M, Farhoudi M and Mahmoudi J: Amyloid-beta: A crucial factor in Alzheimer's disease. Med Princ Pract. 24:1–10. 2015. View Article : Google Scholar : PubMed/NCBI
6	Yin F, Boveris A and Cadenas E: Mitochondrial energy metabolism and redox signaling in brain aging and neurodegeneration. Antioxid Redox Signal. 20:353–371. 2014. View Article : Google Scholar : PubMed/NCBI
7	Wang R, Li JJ, Diao S, Kwak YD, Liu L, Zhi L, Büeler H, Bhat NR, Williams RW, Park EA and Liao FF: Metabolic stress modulates Alzheimer's β-secretase gene transcription via SIRT1-PPARγ-PGC-1 in neurons. Cell Metab. 17:685–694. 2013. View Article : Google Scholar : PubMed/NCBI
8	Wu MF, Yin JH, Hwang CS, Tang CM and Yang DI: NAD attenuates oxidative DNA damages induced by amyloid beta-peptide in primary rat cortical neurons. Free Radic Res. 48:794–805. 2014. View Article : Google Scholar : PubMed/NCBI
9	Ussher JR, Jaswal JS and Lopaschuk GD: Pyridine nucleotide regulation of cardiac intermediary metabolism. Circ Res. 111:628–641. 2012. View Article : Google Scholar : PubMed/NCBI
10	Rongvaux A, Shea RJ, Mulks MH, Gigot D, Urbain J, Leo O and Andris F: Pre-B-cell colony-enhancing factor, whose expression is up-regulated in activated lymphocytes, is a nicotinamide phosphoribosyltransferase, a cytosolic enzyme involved in NAD biosynthesis. Eur J Immunol. 32:3225–3234. 2002. View Article : Google Scholar : PubMed/NCBI
11	Ying W: NAD⁺/NADH and NADP⁺/NADPH in cellular functions and cell death: Regulation and biological consequences. Antioxid Redox Signal. 10:179–206. 2008. View Article : Google Scholar : PubMed/NCBI
12	Revollo JR, Grimm AA and Imai S: The regulation of nicotinamide adenine dinucleotide biosynthesis by Nampt/PBEF/visfatin in mammals. Curr Opin Gastroenterol. 23:164–170. 2007. View Article : Google Scholar : PubMed/NCBI
13	Villela D, Schlesinger D, Suemoto CK, Grinberg LT and Rosenberg C: A microdeletion in Alzheimer's disease disrupts NAMPT gene. J Genet. 93:535–537. 2014. View Article : Google Scholar : PubMed/NCBI
14	Imai S and Guarente L: NAD⁺ and sirtuins in aging and disease. Trends Cell Biol. 24:464–471. 2014. View Article : Google Scholar : PubMed/NCBI
15	Herrera-Arozamena C, Martí-Marí O, Estrada M, de la Fuente Revenga M and Rodríguez-Franco MI: Recent advances in neurogenic small molecules as innovative treatments for neurodegenerative diseases. Molecules. 21:pii: E1165. 2016. View Article : Google Scholar : PubMed/NCBI
16	Qi Z, Qi S, Ling L, Lv J and Feng Z: Salidroside attenuates inflammatory response via suppressing JAK2-STAT3 pathway activation and preventing STAT3 transfer into nucleus. Int Immunopharmacol. 35:265–271. 2016. View Article : Google Scholar : PubMed/NCBI
17	Yang ZR, Wang HF, Zuo TC, Guan LL and Dai N: Salidroside alleviates oxidative stress in the liver with non- alcoholic steatohepatitis in rats. BMC Pharmacol Toxicol. 17:162016. View Article : Google Scholar : PubMed/NCBI
18	Sun KX, Xia HW and Xia RL: Anticancer effect of salidroside on colon cancer through inhibiting JAK2/STAT3 signaling pathway. Int J Clin Exp Pathol. 8:615–621. 2015.PubMed/NCBI
19	Zhang B, Wang Y, Li H, Xiong R, Zhao Z, Chu X, Li Q, Sun S and Chen S: Neuroprotective effects of salidroside through PI3K/Akt pathway activation in Alzheimer's disease models. Drug Des Devel Ther. 10:1335–1343. 2016.PubMed/NCBI
20	Gao J, Zhou R, You X, Luo F, He H, Chang X, Zhu L, Ding X and Yan T: Salidroside suppresses inflammation in a D-galactose-induced rat model of Alzheimer's disease via SIRT1/NF-κB pathway. Metab Brain Dis. 31:771–778. 2016. View Article : Google Scholar : PubMed/NCBI
21	Zhang W, Peng M, Yang Y, Xiao Z, Song B and Lin Z: Protective effects of salidroside on mitochondrial functions against exertional heat stroke-induced organ damage in the rat. Evid Based Complement Alternat Med. 2015:5045672015. View Article : Google Scholar : PubMed/NCBI
22	Yang Y and Sauve AA: NAD⁺ metabolism: Bioenergetics, signaling and manipulation for therapy. Biochim Biophys Acta. 1864:1787–1800. 2016. View Article : Google Scholar : PubMed/NCBI
23	Selkoe DJ and Schenk D: Alzheimer's disease: Molecular understanding predicts amyloid-based therapeutics. Annu Rev Pharmacol Toxicol. 43:545–584. 2003. View Article : Google Scholar : PubMed/NCBI
24	Cheng YF, Wang C, Lin HB, Li YF, Huang Y, Xu JP and Zhang HT: Inhibition of phosphodiesterase-4 reverses memory deficits produced by Aβ_25–35 or Aβ_1–40 peptide in rats. Psychopharmacology (Berl). 212:181–191. 2010. View Article : Google Scholar : PubMed/NCBI
25	Miguel-Hidalgo JJ and Cacabelos R: Beta-amyloid(1–40)-induced neurodegeneration in the rat hippocampal neurons of the CA1 subfield. Acta Neuropathol. 95:455–465. 1998. View Article : Google Scholar : PubMed/NCBI
26	Yue T, Shanbin G, Ling M, Yuan W, Ying X and Ping Z: Sevoflurane aggregates cognitive dysfunction and hippocampal oxidative stress induced by β-amyloid in rats. Life Sci. 143:194–201. 2015. View Article : Google Scholar : PubMed/NCBI
27	He F, Cao YP, Che FY, Yang LH, Xiao SH and Liu J: Inhibitory effects of edaravone in β-amyloid-induced neurotoxicity in rats. Biomed Res Int. 2014:3703682014. View Article : Google Scholar : PubMed/NCBI
28	Carrillo-Mora P, Luna R and Colín-Barenque L: Amyloid beta: Multiple mechanisms of toxicity and only some protective effects? Oxid Med Cell Longev. 2014:7953752014. View Article : Google Scholar : PubMed/NCBI
29	Han XH, Cheng MN, Chen L, Fang H, Wang LJ, Li XT and Qu ZQ: 7,8-Dihydroxyflavone protects PC12 cells against 6-hydroxydopamine-induced cell death through modulating PI3K/Akt and JNK pathways. Neurosci Lett. 581:85–88. 2014. View Article : Google Scholar : PubMed/NCBI
30	Guo M, Li D, Shen H, Jin B, Ren Y, Li M and Xing Y: Leptin-Sensitive JAK2 activation in the regulation of Tau phosphorylation in PC12 cells. Neurosignals. 24:88–94. 2016. View Article : Google Scholar : PubMed/NCBI
31	Chen CL, Tsai WH, Chen CJ and Pan TM: Centella asiatica extract protects against amyloid β1-40-induced neurotoxicity in neuronal cells by activating the antioxidative defence system. J Tradit Complement Med. 6:362–369. 2015. View Article : Google Scholar : PubMed/NCBI
32	Qian MC, Liu J, Yao JS, Wang WM, Yang JH, Wei LL, Shen YD and Chen W: Caspase-8 mediates amyloid-β-induced apoptosis in differentiated PC12 cells. J Mol Neurosci. 56:491–499. 2015. View Article : Google Scholar : PubMed/NCBI
33	Jieyu H, Chao T, Mengjun L, Shalong W, Xiaomei G, Jianfeng L and Zhihong L: Nampt/Visfatin/PBEF: A functionally multi-faceted protein with a pivotal role in malignant tumors. Curr Pharm Des. 18:6123–6132. 2012. View Article : Google Scholar : PubMed/NCBI
34	Ghosh D, Levault KR and Brewer GJ: Relative importance of redox buffers GSH and NAD(P)H in age-related neurodegeneration and Alzheimer disease-like mouse neurons. Aging Cell. 13:631–640. 2014. View Article : Google Scholar : PubMed/NCBI
35	Stein LR, Wozniak DF, Dearborn JT, Kubota S, Apte RS, Izumi Y, Zorumski CF and Imai S: Expression of Nampt in hippocampal and cortical excitatory neurons is critical for cognitive function. J Neurosci. 34:5800–5815. 2014. View Article : Google Scholar : PubMed/NCBI
36	Cabezas-Opazo FA, Vergara-Pulgar K, Pérez MJ, Jara C, Osorio-Fuentealba C and Quintanilla RA: Mitochondrial dysfunction contributes to the pathogenesis of Alzheimer's disease. Oxid Med Cell Longev. 2015:5096542015. View Article : Google Scholar : PubMed/NCBI
37	Zhu XH, Lu M, Lee BY, Ugurbil K and Chen W: In vivo NAD assay reveals the intracellular NAD contents and redox state in healthy human brain and their age dependences. Proc Natl Acad Sci USA. 112:2876–2881. 2015. View Article : Google Scholar : PubMed/NCBI
38	Wang Y: Molecular links between caloric restriction and Sir2/SIRT1 activation. Diabetes Metab J. 38:321–329. 2014. View Article : Google Scholar : PubMed/NCBI
39	Rodgers JT, Lerin C, Gerhart-Hines Z and Puigserver P: Metabolic adaptations through the PGC-1 alpha and SIRT1 pathways. FEBS Lett. 582:46–53. 2008. View Article : Google Scholar : PubMed/NCBI
40	Katsouri L, Parr C, Bogdanovic N, Willem M and Sastre M: PPARγ co-activator-1α (PGC-1α) reduces amyloid-β generation through a PPARγ-dependent mechanism. J Alzheimers Dis. 25:151–162. 2011.PubMed/NCBI
41	Yoshino J, Mills KF, Yoon MJ and Imai S: Nicotinamide mononucleotide, a key NAD(+) intermediate, treats the pathophysiology of diet- and age-induced diabetes in mice. Cell Metab. 14:528–536. 2011. View Article : Google Scholar : PubMed/NCBI
42	Ghosh D, LeVault KR, Barnett AJ and Brewer GJ: A reversible early oxidized redox state that precedes macromolecular ROS damage in aging nontransgenic and 3xTg-AD mouse neurons. J Neurosci. 32:5821–5832. 2012. View Article : Google Scholar : PubMed/NCBI