Anti-aging Klotho Protects SH-SY5Y Cells Against Amyloid β1–42 Neurotoxicity: Involvement of Wnt1/pCREB/Nrf2/HO-1 Signaling

Springer Science and Business Media LLC - Tập 71 - Trang 19-27 - 2020
Mohsen Sedighi1,2, Tourandokht Baluchnejadmojarad1,3, Siamak Afshin-Majd4,5, Mona Amiri3, Malihe Aminzade6, Mehrdad Roghani4
1Department of Neuroscience, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran
2Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran
3Department of Physiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
4Neurophysiology Research Center, Shahed University, Tehran, Iran
5Department of Neurology, School of Medicine, Shahed University, Tehran, Iran
6Institute of Biochemistry and Biophysics (IBB), University of Tehran, Tehran, Iran

Tóm tắt

Alzheimer’s disease (AD) is considered a prevalent neurological disorder with a neurodegenerative nature in elderly people. Oxidative stress and neuroinflammation due to amyloid β (Aβ) peptides are strongly involved in AD pathogenesis. Klotho is an anti-aging protein with multiple protective effects that its deficiency is involved in development of age-related disorders. In this study, we investigated the beneficial effect of Klotho pretreatment at different concentrations of 0.5, 1, and 2 nM against Aβ1–42 toxicity at a concentration of 20 μM in human SH-SY5Y neuroblastoma cells. Our findings showed that Klotho could significantly and partially restore cell viability and decrease reactive oxygen species (known as ROS) and improve superoxide dismutase activity (SOD) in addition to reduction of caspase 3 activity and DNA fragmentation following Aβ1–42 challenge. In addition, exogenous Klotho also reduced inflammatory biomarkers consisting of nuclear factor-kB (NF-kB), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) in Aβ-exposed cells. Besides, Klotho caused downregulation of Wnt1 level, upregulation of phosphorylated cyclic AMP response element binding (pCREB), and mRNA levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) with no significant alteration of epsilon isoform of protein kinase C (PKCε) after Aβ toxicity. In summary, Klotho could alleviate apoptosis, oxidative stress, and inflammation in human neuroblastoma cells after Aβ challenge and its beneficial effect is partially exerted through appropriate modulation of Wnt1/pCREB/Nrf2/HO-1 signaling.

Tài liệu tham khảo

Baluchnejadmojarad T, Eftekhari SM, Jamali-Raeufy N, Haghani S, Zeinali H, Roghani M (2017) The anti-aging protein klotho alleviates injury of nigrostriatal dopaminergic pathway in 6-hydroxydopamine rat model of Parkinson’s disease: involvement of PKA/CaMKII/CREB signaling. Exp Gerontol 100:70–76. https://doi.org/10.1016/j.exger.2017.10.023 Boyd-Kimball D, Castegna A, Sultana R, Poon HF, Petroze R, Lynn BC, Klein JB, Butterfield DA (2005) Proteomic identification of proteins oxidized by Aβ (1–42) in synaptosomes: implications for Alzheimer’s disease. Brain Res 1044(2):206–215 Brewer GJ, Torricelli JR, Lindsey AL, Kunz EZ, Neuman A, Fisher DR, Joseph JA (2010) Age-related toxicity of amyloid-beta associated with increased pERK and pCREB in primary hippocampal neurons: reversal by blueberry extract. J Nutr Biochem 21(10):991–998. https://doi.org/10.1016/j.jnutbio.2009.08.005 Brobey RK, German D, Sonsalla PK, Gurnani P, Pastor J, Hsieh CC, Papaconstantinou J, Foster PP, Kuro-o M, Rosenblatt KP (2015) Klotho protects dopaminergic neuron oxidant-induced degeneration by modulating ASK1 and p38 MAPK signaling pathways. PLoS One 10(10):e0139914. https://doi.org/10.1371/journal.pone.0139914 Choi DS, Wang D, Yu GQ, Zhu G, Kharazia VN, Paredes JP, Chang WS, Deitchman JK, Mucke L, Messing RO (2006) PKCepsilon increases endothelin converting enzyme activity and reduces amyloid plaque pathology in transgenic mice. Proc Natl Acad Sci U S A 103(21):8215–8220. https://doi.org/10.1073/pnas.0509725103 Chong ZZ, Li F, Maiese K (2005) Erythropoietin requires NF-kappaB and its nuclear translocation to prevent early and late apoptotic neuronal injury during beta-amyloid toxicity. Curr Neurovasc Res 2(5):387–399 Cui W, Leng B, Wang G (2019) Klotho protein inhibits H2O2-induced oxidative injury in endothelial cells via regulation of PI3K/AKT/Nrf2/HO-1 pathways. Can J Physiol Pharmacol 97(5):370–376. https://doi.org/10.1139/cjpp-2018-0277 Fakhar M, Najumuddin, Gul M, Rashid S (2018) Antagonistic role of Klotho-derived peptides dynamics in the pancreatic cancer treatment through obstructing WNT-1 and frizzled binding. Biophys Chem 240:107–117. https://doi.org/10.1016/j.bpc.2018.07.002 Gill I, Kaur S, Kaur N, Dhiman M, Mantha AK (2017) Phytochemical ginkgolide B attenuates amyloid-beta1-42 induced oxidative damage and altered cellular responses in human neuroblastoma SH-SY5Y cells. J Alzheimers Dis 60(s1):S25–s40. https://doi.org/10.3233/jad-161086 Haass C, Selkoe DJ (2007) Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer’s amyloid β-peptide. Nat Rev Mol Cell Biol 8(2):101–112 Hongpaisan J, Sun MK, Alkon DL (2011) PKC ε activation prevents synaptic loss, Aβ elevation, and cognitive deficits in Alzheimer’s disease transgenic mice. J Neurosci 31(2):630–643. https://doi.org/10.1523/jneurosci.5209-10.2011 Imai M, Ishikawa K, Matsukawa N, Kida I, Ohta J, Ikushima M, Chihara Y, Rui X, Rakugi H, Ogihara T (2004) Klotho protein activates the PKC pathway in the kidney and testis and suppresses 25-hydroxyvitamin D3 1alpha-hydroxylase gene expression. Endocrine 25(3):229–234. https://doi.org/10.1385/endo:25:3:229 Inestrosa NC, Arenas E (2010) Emerging roles of Wnts in the adult nervous system. Nat Rev Neurosci 11(2):77–86. https://doi.org/10.1038/nrn2755 Inestrosa NC, Toledo EM (2008) The role of Wnt signaling in neuronal dysfunction in Alzheimer’s disease. Mol Neurodegener 3(1):9. https://doi.org/10.1186/1750-1326-3-9 Karran E, Mercken M, De Strooper B (2011) The amyloid cascade hypothesis for Alzheimer’s disease: an appraisal for the development of therapeutics. Nat Rev Drug Discov 10(9):698–712 Kokkinaki M, Abu-Asab M, Gunawardena N, Ahern G, Javidnia M, Young J, Golestaneh N (2013) Klotho regulates retinal pigment epithelial functions and protects against oxidative stress. J Neurosci 33(41):16346–16359. https://doi.org/10.1523/jneurosci.0402-13.2013 Krick S, Grabner A, Baumlin N, Yanucil C, Helton S, Grosche A, Sailland J, Geraghty P, Viera L, Russell DW, Wells JM, Xu X, Gaggar A, Barnes J, King GD, Campos M, Faul C, Salathe M (2018) Fibroblast growth factor 23 and Klotho contribute to airway inflammation. Eur Respir J 52(1):1800236. https://doi.org/10.1183/13993003.00236-2018 Kuro-o M, Matsumura Y, Aizawa H, Kawaguchi H, Suga T, Utsugi T et al (1997) Mutation of the mouse klotho gene leads to a syndrome resembling ageing. Nature 390(6655):45–51. https://doi.org/10.1038/36285 Lee W, Boo JH, Jung MW, Park SD, Kim YH, Kim SU, Mook-Jung I (2004) Amyloid beta peptide directly inhibits PKC activation. Mol Cell Neurosci 26(2):222–231. https://doi.org/10.1016/j.mcn.2003.10.020 Lee B, Cao R, Choi YS, Cho HY, Rhee AD, Hah CK, Hoyt KR, Obrietan K (2009) The CREB/CRE transcriptional pathway: protection against oxidative stress-mediated neuronal cell death. J Neurochem 108(5):1251–1265. https://doi.org/10.1111/j.1471-4159.2008.05864.x Li S-A, Watanabe M, Yamada H, Nagai A, Kinuta M, Takei K (2004) Immunohistochemical localization of Klotho protein in brain, kidney, and reproductive organs of mice. Cell Struct Funct 29(4):91–99. https://doi.org/10.1247/csf.29.9 Li Y, Liu Q, Sun J, Wang J, Liu X, Gao J (2018) Mitochondrial protective mechanism of simvastatin protects against amyloid beta peptide-induced injury in SH-SY5Y cells. Int J Mol Med 41(5):2997–3005. https://doi.org/10.3892/ijmm.2018.3456 Liang H, Yang K, Xin M, Liu X, Zhao L, Liu B, Wang J (2017) MiR-130a protects against lipopolysaccharide-induced glomerular cell injury by upregulation of Klotho. Pharmazie 72(8):468–474. https://doi.org/10.1691/ph.2017.7525 Mackay K, Mochly-Rosen D (2001) Localization, anchoring, and functions of protein kinase C isozymes in the heart. J Mol Cell Cardiol 33(7):1301–1307. https://doi.org/10.1006/jmcc.2001.1400 Monsell SE, Mock C, Hassenstab J, Roe CM, Cairns NJ, Morris JC, Kukull W (2014) Neuropsychological changes in asymptomatic persons with Alzheimer disease neuropathology. Neurology 83(5):434–440. https://doi.org/10.1212/WNL.0000000000000650 Movsesyan VA, Yakovlev AG, Dabaghyan EA, Stoica BA, Faden AI (2002) Ceramide induces neuronal apoptosis through the caspase-9/caspase-3 pathway. Biochem Biophys Res Commun 299(2):201–207 Oguchi T, Ono R, Tsuji M, Shozawa H, Somei M, Inagaki M, Mori Y, Yasumoto T, Ono K, Kiuchi Y (2017) Cilostazol suppresses Abeta-induced neurotoxicity in SH-SY5Y cells through inhibition of oxidative stress and MAPK signaling pathway. Front Aging Neurosci 9:337. https://doi.org/10.3389/fnagi.2017.00337 Park SJ, Park SH, Chang JW, Choi J, Jung HH, Im GJ (2012) Protective effect of klotho protein against cisplatin ototoxicity in an auditory cell line. J Laryngol Otol 126(10):1003–1009. https://doi.org/10.1017/s0022215112001715 Pugazhenthi S, Wang M, Pham S, Sze CI, Eckman CB (2011) Downregulation of CREB expression in Alzheimer’s brain and in Abeta-treated rat hippocampal neurons. Mol Neurodegener 6:60. https://doi.org/10.1186/1750-1326-6-60 Rojas-Gutierrez E, Munoz-Arenas G, Trevino S, Espinosa B, Chavez R, Rojas K et al (2017) Alzheimer’s disease and metabolic syndrome: a link from oxidative stress and inflammation to neurodegeneration. Synapse. 71:e21990. https://doi.org/10.1002/syn.21990 Salinas PC (2012) Wnt signaling in the vertebrate central nervous system: from axon guidance to synaptic function. Cold Spring Harb Perspect Biol 4(2). https://doi.org/10.1101/cshperspect.a008003 Sedighi M, Baluchnejadmojarad T, Fallah S, Moradi N, Afshin-Majdd S, Roghani M (2019) Klotho ameliorates cellular inflammation via suppression of cytokine release and upregulation of miR-29a in the PBMCs of diagnosed Alzheimer’s disease patients. J Mol Neurosci 69(1):157–165. https://doi.org/10.1007/s12031-019-01345-5 Sharma S, Verma S, Kapoor M, Saini A, Nehru B (2016) Alzheimer’s disease like pathology induced six weeks after aggregated amyloid-beta injection in rats: increased oxidative stress and impaired long-term memory with anxiety-like behavior. Neurol Res 38(9):838–850. https://doi.org/10.1080/01616412.2016.1209337 Shi C, Wu F, Yew DT, Xu J, Zhu Y (2010) Bilobalide prevents apoptosis through activation of the PI3K/Akt pathway in SH-SY5Y cells. Apoptosis 15(6):715–727. https://doi.org/10.1007/s10495-010-0492-x Shiozaki M, Yoshimura K, Shibata M, Koike M, Matsuura N, Uchiyama Y, Gotow T (2008) Morphological and biochemical signs of age-related neurodegenerative changes in klotho mutant mice. Neuroscience 152(4):924–941 Sopjani M, Rinnerthaler M, Kruja J, Dermaku-Sopjani M (2015) Intracellular signaling of the aging suppressor protein Klotho. Curr Mol Med 15(1):27–37 Spires-Jones TL, Hyman BT (2014) The intersection of amyloid beta and tau at synapses in Alzheimer’s disease. Neuron 82(4):756–771. https://doi.org/10.1016/j.neuron.2014.05.004 Sun X, Chen WD, Wang YD (2015) β-Amyloid: the key peptide in the pathogenesis of Alzheimer’s disease. Front Pharmacol 6:221. https://doi.org/10.3389/fphar.2015.00221 Tapia-Rojas C, Inestrosa NC (2018) Wnt signaling loss accelerates the appearance of neuropathological hallmarks of Alzheimer’s disease in J20-APP transgenic and wild-type mice. J Neurochem 144(4):443–465. https://doi.org/10.1111/jnc.14278 Tiong CX, Lu M, Bian JS (2010) Protective effect of hydrogen sulphide against 6-OHDA-induced cell injury in SH-SY5Y cells involves PKC/PI3K/Akt pathway. Br J Pharmacol 161(2):467–480. https://doi.org/10.1111/j.1476-5381.2010.00887.x Verdile G, Keane KN, Cruzat VF, Medic S, Sabale M, Rowles J, Newsholme P (2015) Inflammation and oxidative stress: the molecular connectivity between insulin resistance, obesity, and Alzheimer’s disease. Mediat Inflamm 2015:105828–105817. https://doi.org/10.1155/2015/105828 Walsh DM, Klyubin I, Fadeeva JV, Cullen WK, Anwyl R, Wolfe MS, Rowan MJ, Selkoe DJ (2002) Naturally secreted oligomers of amyloid β protein potently inhibit hippocampal long-term potentiation in vivo. Nature 416(6880):535–539 Wang Y, Sun Z (2009) Current understanding of klotho. Ageing Res Rev 8(1):43–51. https://doi.org/10.1016/j.arr.2008.10.002 Wang SW, Wang YJ, Su YJ, Zhou WW, Yang SG, Zhang R, Zhao M, Li YN, Zhang ZP, Zhan DW, Liu RT (2012) Rutin inhibits beta-amyloid aggregation and cytotoxicity, attenuates oxidative stress, and decreases the production of nitric oxide and proinflammatory cytokines. Neurotoxicology 33(3):482–490. https://doi.org/10.1016/j.neuro.2012.03.003 Wang W, Wang W, Yao G, Ren Q, Wang D, Wang Z, Liu P, Gao P, Zhang Y, Wang S, Song S (2018) Novel sarsasapogenin-triazolyl hybrids as potential anti-Alzheimer’s agents: design, synthesis and biological evaluation. Eur J Med Chem 151:351–362. https://doi.org/10.1016/j.ejmech.2018.03.082 Weinreb O, Bar-Am O, Amit T, Chillag-Talmor O, Youdim MB (2004) Neuroprotection via pro-survival protein kinase C isoforms associated with Bcl-2 family members. FASEB J 18(12):1471–1473. https://doi.org/10.1096/fj.04-1916fje Xu N, Xiao Z, Zou T, Huang Z (2015) Induction of GADD34 regulates the neurotoxicity of amyloid beta. Am J Alzheimers Dis Other Dement 30(3):313–319. https://doi.org/10.1177/1533317514545616 Yeo ETY, Wong KWL, See ML, Wong KY, Gan SY, Chan EWL (2018) Piper sarmentosum Roxb. confers neuroprotection on beta-amyloid (Abeta)-induced microglia-mediated neuroinflammation and attenuates tau hyperphosphorylation in SH-SY5Y cells. J Ethnopharmacol 217:187–194. https://doi.org/10.1016/j.jep.2018.02.025 Yu M-S, Suen K-C, Kwok N-S, So K-F, Hugon J, Chang RC-C (2006) Beta-amyloid peptides induces neuronal apoptosis via a mechanism independent of unfolded protein responses. Apoptosis 11(5):687–700 Zeldich E, Chen CD, Colvin TA, Bove-Fenderson EA, Liang J, Tucker Zhou TB, Harris DA, Abraham CR (2014) The neuroprotective effect of Klotho is mediated via regulation of members of the redox system. J Biol Chem 289(35):24700–24715. https://doi.org/10.1074/jbc.M114.567321 Zhou X, Li Y, Shi X, Ma C (2016) An overview on therapeutics attenuating amyloid beta level in Alzheimer’s disease: targeting neurotransmission, inflammation, oxidative stress and enhanced cholesterol levels. Am J Transl Res 8(2):246–269 Zhou C, Zhao L, Zheng J, Wang K, Deng H, Liu P, Chen L, Mu H (2017a) MicroRNA-144 modulates oxidative stress tolerance in SH-SY5Y cells by regulating nuclear factor erythroid 2-related factor 2-glutathione axis. Neurosci Lett 655:21–27. https://doi.org/10.1016/j.neulet.2017.06.045 Zhou HJ, Li H, Shi MQ, Mao XN, Liu DL, Chang YR et al (2017b) Protective effect of Klotho against ischemic brain injury is associated with inhibition of RIG-I/NF-kappaB signaling. Front Pharmacol 8:950. https://doi.org/10.3389/fphar.2017.00950 Zhou Y, Kuang Y, Zhou J (2017c) Klotho protects against LPS-induced inflammation injury by inhibiting Wnt and NF-kappaB pathways in HK-2 cells. Pharmazie 72(4):227–231. https://doi.org/10.1691/ph.2017.6867 Zhou HJ, Zeng CY, Yang TT, Long FY, Kuang X, Du JR (2018) Lentivirus-mediated klotho up-regulation improves aging-related memory deficits and oxidative stress in senescence-accelerated mouse prone-8 mice. Life Sci 200:56–62. https://doi.org/10.1016/j.lfs.2018.03.027