DOI QR코드

DOI QR Code

Neurotoxin-Induced Pathway Perturbation in Human Neuroblastoma SH-EP Cells

  • Do, Jin Hwan (Department of Biomolecular and Chemical Engineering, DongYang University)
  • Received : 2014.06.23
  • Accepted : 2014.08.11
  • Published : 2014.09.30

Abstract

The exact causes of cell death in Parkinson's disease (PD) remain unknown despite extensive studies on PD.The identification of signaling and metabolic pathways involved in PD might provide insight into the molecular mechanisms underlying PD. The neurotoxin 1-methyl-4-phenylpyridinium ($MPP^+$) induces cellular changes characteristic of PD, and $MPP^+$-based models have been extensively used for PD studies. In this study, pathways that were significantly perturbed in $MPP^+$-treated human neuroblastoma SH-EP cells were identified from genome-wide gene expression data for five time points (1.5, 3, 9, 12, and 24 h) after treatment. The mitogen-activated protein kinase (MAPK) signaling pathway and endoplasmic reticulum (ER) protein processing pathway showed significant perturbation at all time points. Perturbation of each of these pathways resulted in the common outcome of upregulation of DNA-damage-inducible transcript 3 (DDIT3). Genes involved in ER protein processing pathway included ubiquitin ligase complex genes and ER-associated degradation (ERAD)-related genes. Additionally, overexpression of DDIT3 might induce oxidative stress via glutathione depletion as a result of overexpression of CHAC1. This study suggests that upregulation of DDIT3 caused by perturbation of the MAPK signaling pathway and ER protein processing pathway might play a key role in $MPP^+$-induced neuronal cell death. Moreover, the toxicity signal of $MPP^+$ resulting from mitochondrial dysfunction through inhibition of complex I of the electron transport chain might feed back to the mitochondria via ER stress. This positive feedback could contribute to amplification of the death signal induced by $MPP^+$.

Acknowledgement

Supported by : National Research Foundation of Korea (NRF)

References

  1. Almeida, R.D., Manadas, B.J., Melo, C.V., Gomes, J.R., Mendes, C.S., Graos, M.M., Carvalho, R.F., Carvalho, A.P., and Duarte, C.B. (2005). Neuroprotection by BDNF against glutamateinduced apoptotic cell death is mediated by ERK and PI3-kinase pathways. Cell Death Differ. 12, 1329-1343. https://doi.org/10.1038/sj.cdd.4401662
  2. Bandiera, S., Rüberg, S., Girard, M., Cagnard, N., Hanein, S., Chretien, D., Munnich, A., Lyonnet, S., and Henrion-Caude, A. (2011). PLos One 6, e20746. https://doi.org/10.1371/journal.pone.0020746
  3. Benjamini, Y., and Yekutieli, D. (2001).The control of the false discovery rate in multiple testing under dependency. Ann. Stat. 29, 1165-1188. https://doi.org/10.1214/aos/1013699998
  4. Conn, K.J., Gao, W.W., Ullman, M.D., McKeon-O'Malley, C., Eisenhaur, P.B., Fine, R.E., and Wells, J.M. (2002). Specific upregulation of GADD153/CHOP in 1-methyl-4-phenyl-pyridiniumtreated SH-SY5Y cells. J. Neurosci. Res. 68, 755-760. https://doi.org/10.1002/jnr.10252
  5. Conn, K.J., Ullman, M.D., Larned, M.J., Eisenhauer, P.B., Fine, R.E., and Wells, J.M. (2003). cDNA microarray analysis of changes in gene expression associated with $MPP^+$ toxicity in SH-SY5Y cells. Neurochem. Res. 28, 1873-1881. https://doi.org/10.1023/A:1026179926780
  6. Croft, D., Mundo, A.F., Haw, R., Milacic, M., Weiser, J., Wu, G., Caudy, M., Garapati, P., Gillespie, M., Kamdar, M.R., et al. (2014). The Reactome pathway knowledgebase. Nucleic Acids Res. 42, D472-D477. https://doi.org/10.1093/nar/gkt1102
  7. Date, I., Yoshimoto, Y., Imaoka, T., Miyoshi, Y., Gohda, Y., Furuta, T., Asari, S., and Ohmoto, T. (1993). Enhanced recovery of the nigrostriatal dopaminergic system in MPTP-treated mice following intrastriatal injection of basic fibroblast growth factor in relation to aging. Brain Res. 621, 150-154. https://doi.org/10.1016/0006-8993(93)90312-B
  8. Do, J.H., Kim, I.S., Lee, J.D., and Choi, D.-K. (2011). Comparison of genomic profiles in human neuroblastic SH-SY5Y and substrateadherent SH-EP cells using array comparative genomic hybridization. BioChip J. 5, 165-174. https://doi.org/10.1007/s13206-011-5210-4
  9. Doniger, S.W., Salomonis, N., Dahlquist, K.D., Vranizan, K., Lawlor, S.C., and Conklin, R.R. (2003). MAPPfinder: using Gene Ontology and GenMAPP to create a global gene expression profile from microarray data. Genome Biol. 4, R7. https://doi.org/10.1186/gb-2003-4-1-r7
  10. Drăghici, S., Khatri, P., Martins, R.P., Ostermeier, G.C., and Krawetz, S.A. (2003). Global functional profiling of gene expression. Genomics 81, 98-104. https://doi.org/10.1016/S0888-7543(02)00021-6
  11. Galvez-Jimenez, N. (2007). Parkinson's disease. In Neurobiology of Disease, S. Gilman, ed. (USA: Elsevier Academic Press), p. 55.
  12. Ghribi, O., Herman, M.M., Pramoonjago, P., and Savory, J. (2003). $MPP^+$ induces the endoplasmic reticulum stress response in rabbit brain involving activation of the ATF-6 and NF-kappaB signaling pathways. J. Neuropathol. Exp. Neurol. 62, 1144-1153. https://doi.org/10.1093/jnen/62.11.1144
  13. Goeman, J.J., van de Geer, S.A., de Kort, F., and van Houwelingen, H.C. (2004). A global test for groups of genes: testing association with a clinical outcome. Bioinformatics 20, 93-99. https://doi.org/10.1093/bioinformatics/btg382
  14. Gotoh, T., Takeda, K., Oyadomari, S., and Mori, M. (2004). hsp70-DnaJ chaperone pair prevents nitric oxide-, CHOP-induced apoptosis by inhibiting translocation of Bax to mitochondria. Cell Death Differ. 11, 390-402. https://doi.org/10.1038/sj.cdd.4401369
  15. Hochberg, Y. (1988). A sharper Bonferroni procedure for multiple tests of significance. Biometrika 75, 800-802. https://doi.org/10.1093/biomet/75.4.800
  16. Hoevel, T., Macek, R., Swisshelm, K., and Kubbies, M. (2004). Reexpression of the TJ protein CLDN1 induces apoptosis in breast tumor spheroids. Int. J. Cancer 108, 374-383. https://doi.org/10.1002/ijc.11571
  17. Kanehisa, M., Goto, S., Sato, Y., Furumichi, M., and Tanabe, M. (2012). KEGG for integration and interpretation of large-scale molecular data sets. Nucleic Acids Res. 40, D109-114. https://doi.org/10.1093/nar/gkr988
  18. Kim, I.S., Choi, D.-K., and Do, J.H. (2013). Genome-wide temporal responses of human neuroblastoma SH-SY5Y cells to $MPP^+$ neurotoxicity. BioChip J. 7, 247-257. https://doi.org/10.1007/s13206-013-7308-3
  19. Kogel, D., Svensson, B., Copanaki, E., Anguissola, S., Bonner, C., Thurow, N., Gudorf, D., Hetschko, H., Muller, T., Peters, M., et al. (2006). Induction of transcription factor CEBP homology protein mediates hypoglycaemia-induced necrotic cell death in human neuroblastoma cells. J. Neurichem. 99, 952-964. https://doi.org/10.1111/j.1471-4159.2006.04135.x
  20. Kumar, A., Tikoo, S., Maity, S., Sengupta, S., Sengupta, S., Kaur, A., and Bachhawat, A.K. (2012). Mammalian proapoptotic factor ChaC1 and its homologues function as $\gamma$-glutamylcyclotransferases acting specifically on glutathione. EMBO Rep. 13, 1095-1101. https://doi.org/10.1038/embor.2012.156
  21. Langston, J.W., Ballard, P., and Irwin, I. (1983). Chronic parkinsonism in human due to a product of meperidine-analog synthesis. Science 219, 979-980. https://doi.org/10.1126/science.6823561
  22. Livak, K.J., and Schmittgen, T.D. (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta DeltaC(T)) method. Methods 25, 402-408. https://doi.org/10.1006/meth.2001.1262
  23. Lotharius, J., and O'Malley, K.L. (2000). The parkinsonism-inducing drug 1-methyl-4-phenylpyridinium triggers intracellular dopamine oxidation. A novel mechanism of toxicity. J. Biol. Chem. 275, 38581-38588. https://doi.org/10.1074/jbc.M005385200
  24. Marciniak, S.J., Yun, C.Y., Oyadomari, S., Novoa, I., Zhang, Y., Jungreis, R., Nagata, K., Harding, H.P., and Ron, D. (2004). CHOP induces death by promoting protein synthesis and oxidation in the stressed endoplasmic reticulum. Genes Dev. 18, 3066-3077. https://doi.org/10.1101/gad.1250704
  25. Matsumoto, M., Minami, M., Takeda, K., Sakao, Y., and Akira, S. (1996). Ectopic expression of CHOP (GADD153) induces apoptosis in M1 myeloblastic leukemia cells. FEBS Lett. 395, 143-147. https://doi.org/10.1016/0014-5793(96)01016-2
  26. McCullough, K.D., Martindale, J.L., Klotz, L.O., Aw, T.Y., and Holbrook, N.J. (2001). Gadd153 sensitizes cells to endoplasmic reticulum stress by down-regulating Bcl2 and perturbing the cellular redox state. Mol. Cell. Biol. 21, 1249-1259. https://doi.org/10.1128/MCB.21.4.1249-1259.2001
  27. Mungrue, I.N., Pagnon, J., Kohannim, O., Gargalovic, P.S., and Lusis, A.J. (2009). CHAC1/MGC4504 is a novel proapoptotic component of the unfolded protein response, downstream of the ATF4-ATF3-CHOP cascade. J. Immunol. 182, 466-476. https://doi.org/10.4049/jimmunol.182.1.466
  28. Nakamura, K., Bindokas, V.P., Marks, J.D., Wright, D.A., Frim, D.M., Miller, R.J., and Kang, U.J. (2000). The selective toxicity of 1- methyl-4-phenylpyridinium to dopaminergic neurons: the role of mitochondria complex I and reactive oxygen species revisited. Mol. Pharmacol. 58, 271-278.
  29. Nanjo, F., Goto, K., Seto, R., Suzuki, M., Sakai, M., and Hara, Y. (1996). Scavenging effects of tea catechins and their derivatives on 1,1-diphenyl-2-picrylhydrazyl radical. Free Radic. Biol. Med. 21, 895-902. https://doi.org/10.1016/0891-5849(96)00237-7
  30. Nicotra, A., and Parvez, S. (2002). Apoptotic molecules and MPTPinduced cell dealth. Neurotoxicol. Teratol. 24, 599-605. https://doi.org/10.1016/S0892-0362(02)00213-1
  31. Oyadomari, S., and Mori, M. (2004). Roles of CHOP/GADD153 in endoplasmic reticulum stress. Cell Death Differ. 11, 381-389. https://doi.org/10.1038/sj.cdd.4401373
  32. Pandey, R., Guru, R.K., and Mount, D.W. (2004). Pathway miner:Extracting gene association networks from molecular pathways for predicting the biological significance of gene expression microarray data. Bioinformatics 20, 2156-2158. https://doi.org/10.1093/bioinformatics/bth215
  33. Pepe, D., and Grassi, M. (2014). Investigating perturbed pathway modules from gene expression data via structural equation models. BMC Bioinformatics 15, 132. https://doi.org/10.1186/1471-2105-15-132
  34. Selvaraj, S., Sun, Y., Watt, J.A., Wang, S., Lei, S., Birnbaumer, L., and Singh, B.B. (2012). Neurotoxin-induced ER stress in mouse dopaminergic neurons involves downregulation of TRPC1 and inhibition of AKT/mTOR signaling. J. Clin. Invest. 122, 1354-1367. https://doi.org/10.1172/JCI61332
  35. Tabuchi, Y., Yunoki, T., Hoshi, N., Suzuki, N., and Kondo, T. (2014). Genes and gene networks involved in sodium fluoride-elicited cell death accompanying endoplasmic reticulum stress in oral epithelial cells. Int. J. Mol. Sci. 15, 8959-8978. https://doi.org/10.3390/ijms15058959
  36. Tarca, A.L., Draghici, S., Khatri, P., Hassan, S.S., Mittal, P., Kim, J.S., Kim, C.J., Kusanovic, J.P., and Romero, R. (2009). A novel signaling pathway impact analysis. Bioinformatics 25, 75-82. https://doi.org/10.1093/bioinformatics/btn577
  37. Tusher, V.G., Tibshirani, R., and Chu, G. (2001). Significance analysis of microarrays applied to the ionizing radiation response. Proc. Natl. Acad. Sci. USA 98, 5116-5121. https://doi.org/10.1073/pnas.091062498
  38. Wang, Y., Barbacioru, C., Hyland, F., Xiao, W., Hunkapiller, K.L., Blake, J., Chan, F., Gonzalez, C., Zhang, L., and Samaha, R.R. (2006). Large scale real-time PCR validation on gene expression measurements from two commercial long-oligonucleotide microarrays. BMC Genomics 7, 59. https://doi.org/10.1186/1471-2164-7-59

Cited by

  1. Comparison of Perturbed Pathways in Two Different Cell Models for Parkinson's Disease with Structural Equation Model 2015, https://doi.org/10.1089/cmb.2015.0156
  2. Genome-wide transcriptional comparison of MPP+ treated human neuroblastoma cells with the state space model vol.2, pp.4, 2015, https://doi.org/10.3934/molsci.2015.4.440
  3. Apomorphine-induced pathway perturbation in MPP+-treated SH-SY5Y cells vol.4, pp.3, 2017, https://doi.org/10.3934/molsci.2017.3.271
  4. Genome-wide transcriptional response of MPP+-treated human neuroblastoma SH-SY5Y cells to apomorphine vol.20, pp.3, 2016, https://doi.org/10.1080/19768354.2016.1191541
  5. Prediction of developmental chemical toxicity based on gene networks of human embryonic stem cells vol.44, pp.12, 2016, https://doi.org/10.1093/nar/gkw450
  6. Neuroprotective effects of phloretin and its glycosylated derivative on rotenone-induced toxicity in human SH-SY5Y neuronal-like cells vol.43, pp.4, 2017, https://doi.org/10.1002/biof.1358
  7. Targeting CB1 and GPR55 Endocannabinoid Receptors as a Potential Neuroprotective Approach for Parkinson’s Disease pp.1559-1182, 2019, https://doi.org/10.1007/s12035-019-1495-4