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Nrf2 Signaling Pathway Mediates the Antioxidative Effects of Taurine Against Corticosterone-Induced Cell Death in HUMAN SK-N-SH Cells

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Abstract

Substantial evidence has shown that elevated circulating corticosteroids or chronic stress contributes to neuronal cell death, cognitive and mental disorders. However, the underlying mechanism is still unclear. Taurine is considered to protect neuronal cells from apoptotic cell death in neurodegenerative diseases and neuropsychiatric disorders. In the present study, the protective effects of taurine against corticosterone (CORT)-induced oxidative damage in SK-N-SH neuronal cells were investigated. The results showed that CORT significantly induced cell death, which was blocked by pretreatment with taurine. Similarly, pretreatment with taurine suppressed CORT-induced apoptotic cell death decreasing the levels of intracellular reactive oxygen species and improving mitochondrial function. Pretreatment with taurine increased the expression of phosphorylated extracellular regulated protein kinases (ERK) as well as the nuclear translocation of nuclear factor (erythroid 2-derived)-like 2 (Nrf2) in the CORT rich environment. Furthermore, administration of the ERK inhibitor U0126 or transient (siRNA) silencing of Nrf2 blocked the protective effects of taurine on cell viability and expression levels of Nrf2 and heme oxygenase-1 (HO-1) in the CORT model of neuronal damage. These results suggest that the Nrf2 signaling pathway may play a role in the protection mechanism of taurine against CORT-induced neuronal oxidative damage.

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References

  1. Munck A, Guyre PM, Holbrook NJ (1984) Physiological functions of glucocorticoids in stress and their relation to pharmacological actions. Endocr Rev 5(1):25–44. doi:10.1210/edrv-5-1-25

    Article  CAS  PubMed  Google Scholar 

  2. Sapolsky RM (2000) Glucocorticoids and hippocampal atrophy in neuropsychiatric disorders. Arch Gen Psychiatry 57(10):925–935

    Article  CAS  PubMed  Google Scholar 

  3. Aihara M, Ida I, Yuuki N, Oshima A, Kumano H, Takahashi K, Fukuda M, Oriuchi N, Endo K, Matsuda H, Mikuni M (2007) HPA axis dysfunction in unmedicated major depressive disorder and its normalization by pharmacotherapy correlates with alteration of neural activity in prefrontal cortex and limbic/paralimbic regions. Psychiatry Res 155(3):245–256. doi:10.1016/j.pscychresns.2006.11.002

    Article  CAS  PubMed  Google Scholar 

  4. Murray F, Smith DW, Hutson PH (2008) Chronic low dose corticosterone exposure decreased hippocampal cell proliferation, volume and induced anxiety and depression like behaviours in mice. Eur J Pharmacol 583(1):115–127. doi:10.1016/j.ejphar.2008.01.014

    Article  CAS  PubMed  Google Scholar 

  5. Chen J, Wang ZZ, Zuo W, Zhang S, Chu SF, Chen NH (2016) Effects of chronic mild stress on behavioral and neurobiological parameters: role of glucocorticoid. Horm Behav 78:150–159. doi:10.1016/j.yhbeh.2015.11.006

    Article  CAS  PubMed  Google Scholar 

  6. Li M, Zhou J, Qian J, Cheng X, Wu H, Li L, Qian C, Su J, Wu D, Burns L, Golden T, Wu N (2016) Target genes involved in corticosterone-induced PC12 cell viability and neurite disorders: a potential molecular mechanism of major depressive disorder. Psychiatry Res 235:206–208. doi:10.1016/j.psychres.2015.11.044

    Article  CAS  PubMed  Google Scholar 

  7. Rohleder N, Wolf JM, Wolf OT (2010) Glucocorticoid sensitivity of cognitive and inflammatory processes in depression and posttraumatic stress disorder. Neurosci Biobehav Rev 35(1):104–114. doi:10.1016/j.neubiorev.2009.12.003

    Article  CAS  PubMed  Google Scholar 

  8. Zhu MY, Wang WP, Bissette G (2006) Neuroprotective effects of agmatine against cell damage caused by glucocorticoids in cultured rat hippocampal neurons. Neuroscience 141(4):2019–2027. doi:10.1016/j.neuroscience.2006.05.011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Alfarez DN, De Simoni A, Velzing EH, Bracey E, Joels M, Edwards FA, Krugers HJ (2009) Corticosterone reduces dendritic complexity in developing hippocampal CA1 neurons. Hippocampus 19(9):828–836. doi:10.1002/hipo.20566

    Article  CAS  PubMed  Google Scholar 

  10. Johnson JA, Johnson DA, Kraft AD, Calkins MJ, Jakel RJ, Vargas MR, Chen PC (2008) The Nrf2-ARE pathway: an indicator and modulator of oxidative stress in neurodegeneration. Ann N Y Acad Sci 1147:61–69. doi:10.1196/annals.1427.036

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Turpaev KT (2013) Keap1-Nrf2 signaling pathway: mechanisms of regulation and role in protection of cells against toxicity caused by xenobiotics and electrophiles. Biochemistry 78(2):111–126. doi:10.1134/S0006297913020016

    CAS  PubMed  Google Scholar 

  12. Nguyen T, Yang CS, Pickett CB (2004) The pathways and molecular mechanisms regulating Nrf2 activation in response to chemical stress. Free Radic Biol Med 37(4):433–441. doi:10.1016/j.freeradbiomed.2004.04.033

    Article  CAS  PubMed  Google Scholar 

  13. Guan L, Jia N, Zhao X, Zhang X, Tang G, Yang L, Sun H, Wang D, Su Q, Song Q, Cai D, Cai Q, Li H, Zhu Z (2013) The involvement of ERK/CREB/Bcl-2 in depression-like behavior in prenatally stressed offspring rats. Brain Res Bull 99:1–8. doi:10.1016/j.brainresbull.2013.08.003

    Article  CAS  PubMed  Google Scholar 

  14. Jia N, Li Q, Sun H, Song Q, Tang G, Sun Q, Wang W, Chen R, Li H, Zhu Z (2015) Alterations of group I mGluRs and BDNF associated with behavioral abnormity in prenatally stressed offspring rats. Neurochem Res 40(5):1074–1082. doi:10.1007/s11064-015-1565-6

    Article  CAS  PubMed  Google Scholar 

  15. Zhu Z, Li X, Chen W, Zhao Y, Li H, Qing C, Jia N, Bai Z, Liu J (2004) Prenatal stress causes gender-dependent neuronal loss and oxidative stress in rat hippocampus. J Neurosci Res 78(6):837–844. doi:10.1002/jnr.20338

    Article  CAS  PubMed  Google Scholar 

  16. Jia N, Yang K, Sun Q, Cai Q, Li H, Cheng D, Fan X, Zhu Z (2010) Prenatal stress causes dendritic atrophy of pyramidal neurons in hippocampal CA3 region by glutamate in offspring rats. Dev Neurobiol 70(2):114–125. doi:10.1002/dneu.20766

    CAS  PubMed  Google Scholar 

  17. Chou CT, Lin WF, Kong ZL, Chen SY, Hwang DF (2013) Taurine prevented cell cycle arrest and restored neurotrophic gene expression in arsenite-treated SH-SY5Y cells. Amino Acids 45(4):811–819. doi:10.1007/s00726-013-1524-y

    Article  CAS  PubMed  Google Scholar 

  18. Toyoda A, Iio W (2013) Antidepressant-like effect of chronic taurine administration and its hippocampal signal transduction in rats. Adv Exp Med Biol 775:29–43. doi:10.1007/978-1-4614-6130-2_3

    Article  CAS  PubMed  Google Scholar 

  19. Sun Q, Hu H, Wang W, Jin H, Feng G, Jia N (2014) Taurine attenuates amyloid beta 1-42-induced mitochondrial dysfunction by activating of SIRT1 in SK-N-SH cells. Biochem Biophys Res Commun 447(3):485–489. doi:10.1016/j.bbrc.2014.04.019

    Article  CAS  PubMed  Google Scholar 

  20. Leon R, Wu H, Jin Y, Wei J, Buddhala C, Prentice H, Wu JY (2009) Protective function of taurine in glutamate-induced apoptosis in cultured neurons. J Neurosci Res 87(5):1185–1194. doi:10.1002/jnr.21926

    Article  CAS  PubMed  Google Scholar 

  21. Jia N, Sun Q, Su Q, Dang S, Chen G (2016) Taurine promotes cognitive function in prenatally stressed juvenile rats via activating the Akt-CREB-PGC1alpha pathway. Redox Biol 10:179–190. doi:10.1016/j.redox.2016.10.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Shivaraj MC, Marcy G, Low G, Ryu JR, Zhao X, Rosales FJ, Goh EL (2012) Taurine induces proliferation of neural stem cells and synapse development in the developing mouse brain. PLoS ONE 7(8):e42935. doi:10.1371/journal.pone.0042935

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Bartolini D, Piroddi M, Tidei C, Giovagnoli S, Pietrella D, Manevich Y, Tew KD, Giustarini D, Rossi R, Townsend DM, Santi C, Galli F (2015) Reaction kinetics and targeting to cellular glutathione S-transferase of the glutathione peroxidase mimetic PhSeZnCl and its D,L-polylactide microparticle formulation. Free Radic Biol Med 78:56–65. doi:10.1016/j.freeradbiomed.2014.10.008

    Article  CAS  PubMed  Google Scholar 

  24. Bartolini D, Commodi J, Piroddi M, Incipini L, Sancineto L, Santi C, Galli F (2015) Glutathione S-transferase pi expression regulates the Nrf2-dependent response to hormetic diselenides. Free Radical Biol Med 88(Pt B):466–480. doi:10.1016/j.freeradbiomed.2015.06.039

    Article  CAS  Google Scholar 

  25. Sapolsky RM, Romero LM, Munck AU (2000) How do glucocorticoids influence stress responses? Integrating permissive, suppressive, stimulatory, and preparative actions. Endocr Rev 21(1):55–89. doi:10.1210/edrv.21.1.0389

    CAS  PubMed  Google Scholar 

  26. Groeneweg FL, Karst H, de Kloet ER, Joels M (2011) Rapid non-genomic effects of corticosteroids and their role in the central stress response. J Endocrinol 209(2):153–167. doi:10.1530/JOE-10-0472

    Article  CAS  PubMed  Google Scholar 

  27. Martinac M, Pehar D, Karlovic D, Babic D, Marcinko D, Jakovljevic M (2014) Metabolic syndrome, activity of the hypothalamic-pituitary-adrenal axis and inflammatory mediators in depressive disorder. Acta Clin Croat. 53(1):55–71

    PubMed  Google Scholar 

  28. Han Z, Gao LY, Lin YH, Chang L, Wu HY, Luo CX, Zhu DY (2016) Neuroprotection of taurine against reactive oxygen species is associated with inhibiting NADPH oxidases. Eur J Pharmacol 777:129–135. doi:10.1016/j.ejphar.2016.03.006

    Article  CAS  PubMed  Google Scholar 

  29. Chong SJ, Low IC, Pervaiz S (2014) Mitochondrial ROS and involvement of Bcl-2 as a mitochondrial ROS regulator. Mitochondrion 19(Pt A):39–48. doi:10.1016/j.mito.2014.06.002

    Article  CAS  PubMed  Google Scholar 

  30. de Oliveira MR, Brasil FB, Andrade CMB (2017) Naringenin attenuates H2O2-induced mitochondrial dysfunction by an Nrf2-dependent mechanism in SH-SY5Y cells. Neurochem Res. doi:10.1007/s11064-017-2376-8

    Google Scholar 

  31. Ong WY, Farooqui T, Koh HL, Farooqui AA, Ling EA (2015) Protective effects of ginseng on neurological disorders. Front Aging Neurosci 7:129. doi:10.3389/fnagi.2015.00129

    Article  PubMed  PubMed Central  Google Scholar 

  32. Ma Q (2013) Role of nrf2 in oxidative stress and toxicity. Annu Rev Pharmacol Toxicol 53:401–426. doi:10.1146/annurev-pharmtox-011112-140320

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Ci X, Lv H, Wang L, Wang X, Peng L, Qin FX, Cheng G (2015) The antioxidative potential of farrerol occurs via the activation of Nrf2 mediated HO-1 signaling in RAW 264.7 cells. Chem Biol Interact 239:192–199. doi:10.1016/j.cbi.2015.06.032

    Article  CAS  PubMed  Google Scholar 

  34. Freitas AE, Egea J, Buendia I, Navarro E, Rada P, Cuadrado A, Rodrigues AL, Lopez MG (2015) Agmatine induces Nrf2 and protects against corticosterone effects in hippocampal neuronal cell line. Mol Neurobiol 51(3):1504–1519. doi:10.1007/s12035-014-8827-1

    Article  CAS  PubMed  Google Scholar 

  35. Qi Z, Ci X, Huang J, Liu Q, Yu Q, Zhou J, Deng X (2017) Asiatic acid enhances Nrf2 signaling to protect HepG2 cells from oxidative damage through Akt and ERK activation. Biomed Pharmacother 88:252–259. doi:10.1016/j.biopha.2017.01.067

    Article  CAS  PubMed  Google Scholar 

  36. Zhang P, Li Y, Du Y, Li G, Wang L, Zhou F (2016) Resveratrol ameliorated vascular calcification by regulating sirt-1 and Nrf2. Transplant Proc 48(10):3378–3386. doi:10.1016/j.transproceed.2016.10.023

    Article  CAS  PubMed  Google Scholar 

  37. Unuma K, Aki T, Matsuda S, Funakoshi T, Yoshida K, Uemura K (2013) Inducer of heme oxygenase-1 cobalt protoporphyrin accelerates autophagy and suppresses oxidative damages during lipopolysaccharide treatment in rat liver. Hepatol Res 43(1):91–96. doi:10.1111/j.1872-034X.2012.01049.x

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (Program Nos. 81500927 & 31200843), the Project Supported by Natural Science Basic Research Plan in Shaanxi Province of China (Program Nos. 2017JM8017 & 2016JM8041) and the Fundamental Research Funds for the Central Universities (No. xjj2015077).

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  1. Institute of Forensic Medicine, Xi’an Jiaotong University Health Science Center, Xi’an, 710061, Shaanxi, People’s Republic of China

    Qinru Sun

  2. Department of Human Anatomy, Histology and Embryology, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, Xi’an, 710061, Shaanxi, People’s Republic of China

    Ning Jia, Jie Yang & Guomin Chen

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Sun, Q., Jia, N., Yang, J. et al. Nrf2 Signaling Pathway Mediates the Antioxidative Effects of Taurine Against Corticosterone-Induced Cell Death in HUMAN SK-N-SH Cells. Neurochem Res 43, 276–286 (2018). https://doi.org/10.1007/s11064-017-2419-1

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