Skip to main content

Advertisement

SpringerLink
Log in

Proteasome Stress Triggers Death of SH-SY5Y and T98G Cells via Different Cellular Mechanisms

  • Original Paper
  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

Overload or dysfunction of ubiquitin–proteasome system (UPS) is implicated in mechanisms of neurodegeneration associated with neurodegenerative diseases, e.g. Parkinson and Alzheimer disease, and ischemia–reperfusion injury. The aim of this study was to investigate the possible association between viability of neuroblastoma SH-SY5Y and glioblastoma T98G cells treated with bortezomib, inhibitor of 26S proteasome, and accumulation of ubiquitin-conjugated proteins with respect to direct cytotoxicity of aggregates of ubiquitin-conjugated proteins. Bortezomib-induced death of SH-SY5Y cells was documented after 24 h of treatment while death of T98G cells was delayed up to 48 h. Already after 4 h of treatment of both SH-SY5Y and T98G cells with bortezomib, increased levels of both ubiquitin-conjugated proteins with molecular mass more than 150 kDa and Hsp70 were observed whereas Hsp90 was elevated in T98G cells and decreased in SH-SY5Y cells. With respect to the cell death mechanism, we have documented bortezomib-induced activation of caspase 3 in SH-SY5Y cells that was probably a result of increased expression of pro-apoptotic proteins, PUMA and Noxa. In T98G cells, bortezomib-induced expression of caspase 4, documented after 24 h of treatment, with further activation of caspase 3, observed after 48 h of treatment. The delay in activation of caspase 3 correlated well with the delay of death of T98G cells. Our results do not support the possibility about direct cytotoxicity of aggregates of ubiquitin-conjugated proteins. They are more consistent with a view that proteasome inhibition is associated with both transcription-dependent and -independent changes in expression of pro-apoptotic proteins and consequent cell death initiation associated with caspase 3 activation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

References

  1. Glickman MH, Ciechanover A (2002) The ubiquitin-proteasome proteolytic pathway: destruction for the sake of construction. Physiol Rev 82:373–428. doi:10.1152/physrev.00027.2001

    Article  CAS  PubMed  Google Scholar 

  2. Schrader EK, Harstad KG, Matouschek A (2009) Targeting proteins for degradation. Nat Chem Biol 5:815–822. doi:10.1038/nchembio.250

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Meredith SC (2005) Protein denaturation and aggregation: Cellular responses to denatured and aggregated proteins. Ann N Y Acad Sci 1066:181–221. doi:10.1196/annals.1363.030

    Article  CAS  PubMed  Google Scholar 

  4. Muchowski PJ, Wacker JL (2005) Modulation of neurodegeneration by molecular chaperones. Nat Rev Neurosci 6:11–22. doi:10.1038/nrn1587

    Article  CAS  PubMed  Google Scholar 

  5. Ciechanover A, Kwon YT (2015) Degradation of misfolded proteins in neurodegenerative diseases: therapeutic targets and strategies. Exp Mol Med 47:e147. doi:10.1038/emm.2014.117

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Asai A, Tanahashi N, Qiu JH, Saito N, Chi S, Kawahara N, Tanaka K, Kirino T (2002) Selective proteasomal dysfunction in the hippocampal CA1 region after transient forebrain ischemia. J Cereb Blood Flow Metab 22:705–710. doi:10.1097/00004647-200206000-00009

    Article  PubMed  Google Scholar 

  7. Luo T, Park Y, Sun X, Liu C, Hu B (2013) Protein misfolding, aggregation, and autophagy after brain ischemia. Transl Stroke Res 4:581–588. doi:10.1007/s12975-013-0299-5

    Article  CAS  PubMed  Google Scholar 

  8. Caldeira MV, Salazar IL, Curcio M, Canzoniero LM, Duarte CB (2014) Role of the ubiquitin-proteasome system in brain ischemia: friend or foe? Prog Neurobiol 112:50–69

    Article  CAS  PubMed  Google Scholar 

  9. Kaushik S, Cuervo AM (2015) Proteostasis and aging. Nat Med 21:1406–1415. doi:10.1038/nm.4001

    Article  CAS  PubMed  Google Scholar 

  10. Iwabuchi M, Sheng H, Thompson JW, Wang L, Dubois LG, Gooden D, Moseley M, Paschen W, Yang W (2014) Characterization of the ubiquitin-modified proteome regulated by transient forebrain ischemia. J Cereb Blood Flow Metab 34:425–432. doi:10.1038/jcbfm.2013.210

    Article  CAS  PubMed  Google Scholar 

  11. Hayashi T, Tanaka J, Kamikubo T, Takada K, Matsuda M (1993) Increase in ubiquitin conjugates dependent on ischemic damage. Brain Res 620:171–173

    Article  CAS  PubMed  Google Scholar 

  12. Hochrainer K, Jackman K, Anrather J, Iadecola C (2012) Reperfusion rather than ischemia drives the formation of ubiquitin aggregates after middle cerebral artery occlusion. Stroke 43:2229–2235. doi:10.1161/STROKEAHA.112.650416

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Racay P, Chomova M, Tatarkova Z, Kaplan P, Hatok J, Dobrota D (2009) Ischemia-induced mitochondrial apoptosis is significantly attenuated by ischemic preconditioning. Cell Mol Neurobiol 29:901–908. doi:10.1007/s10571-009-9373-7

    Article  CAS  PubMed  Google Scholar 

  14. Racay P (2012) Ischaemia-induced protein ubiquitinylation is differentially accompanied with heat-shock protein 70 expression after naïve and preconditioned ischaemia. Cell Mol Neurobiol 32:107–119. doi:10.1007/s10571-011-9740-z

    Article  CAS  PubMed  Google Scholar 

  15. Cheng B, Maffi SK, Martinez AA, Acosta YP, Morales LD, Roberts JL (2011) Insulin-like growth factor-I mediates neuroprotection in proteasome inhibition-induced cytotoxicity in SH-SY5Y cells. Mol Cell Neurosci 47:181–190. doi:10.1016/j.mcn.2011.04.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Cheng B, Martinez AA, Morado J, Scofield V, Roberts JL, Maffi SK (2013) Retinoic acid protects against proteasome inhibition associated cell death in SH-SY5Y cells via the AKT pathway. Neurochem Int 62:31–42. doi:10.1016/j.neuint.2012.10.014

    Article  CAS  PubMed  Google Scholar 

  17. Butts BD, Hudson HR, Linseman DA, Le SS, Ryan KR, Bouchard RJ, Heidenreich KA (2005) Proteasome inhibition elicits a biphasic effect on neuronal apoptosis via differential regulation of pro-survival and pro-apoptotic transcription factors. Mol Cell Neurosci 30:279–289. doi:10.1016/j.mcn.2005.07.011

    Article  CAS  PubMed  Google Scholar 

  18. Suh J, Lee YA, Gwag BJ (2005) Induction and attenuation of neuronal apoptosis by proteasome inhibitors in murine cortical cell cultures. J Neurochem 95:684–694. doi:10.1111/j.1471-4159.2005.03393.x

    Article  CAS  PubMed  Google Scholar 

  19. Yew EH, Cheung NS, Choy MS, Qi RZ, Lee AY, Peng ZF, Melendez AJ, Manikandan J, Koay ES, Chiu LL, Ng WL, Whiteman M, Kandiah J, Halliwell B (2005) Proteasome inhibition by lactacystin in primary neuronal cells induces both potentially neuroprotective and pro-apoptotic transcriptional responses: a microarray analysis. J Neurochem 94:943–956. doi:10.1111/j.1471-4159.2005.03220.x

    Article  CAS  PubMed  Google Scholar 

  20. Choy MS, Chen MJ, Manikandan J, Peng ZF, Jenner AM, Melendez AJ, Cheung NS (2011) Up-regulation of endoplasmic reticulum stress-related genes during the early phase of treatment of cultured cortical neurons by the proteasomal inhibitor lactacystin. J Cell Physiol 226:494–510. doi:10.1002/jcp.22359

    Article  CAS  PubMed  Google Scholar 

  21. Wojcik C, Di Napoli M (2004) Ubiquitin-proteasome system and proteasome inhibition: new strategies in stroke therapy. Stroke 35:1506–1518. doi:10.1161/01.STR.0000126891.93919.4e

    Article  CAS  PubMed  Google Scholar 

  22. Williams AJ, Dave JR, Tortella FC (2006) Neuroprotection with the proteasome inhibitor MLN519 in focal ischemic brain injury: relation to nuclear factor kappaB (NF-kappaB), inflammatory gene expression, and leukocyte infiltration. Neurochem Int 49:106–112. doi:10.1016/j.neuint.2006.03.018

    Article  CAS  PubMed  Google Scholar 

  23. Tsuchiya T, Bonner HP, Engel T, Woods I, Matsushima S, Ward MW, Taki W, Henshall DC, Concannon CG, Prehn JH (2011) Bcl-2 homology domain 3-only proteins Puma and Bim mediate the vulnerability of CA1 hippocampal neurons to proteasome inhibition in vivo. Eur J Neurosci 33:401–408. doi:10.1111/j.1460-9568.2010.07538.x

    Article  PubMed  Google Scholar 

  24. Bonner HP, Concannon CG, Bonner C, Woods I, Ward MW, Prehn JH (2010) Differential expression patterns of Puma and Hsp70 following proteasomal stress in the hippocampus are key determinants of neuronal vulnerability. J Neurochem 114:606–616. doi:10.1111/j.1471-4159.2010.06790.x

    Article  CAS  PubMed  Google Scholar 

  25. Klacanova K, Pilchova I, Klikova K, Racay P (2016) Short chemical ischemia triggers phosphorylation of eIF2α and death of SH-SY5Y cells but not proteasome stress and heat shock protein response in both SH-SY5Y and T98G cells. J Mol Neurosci 58:497–506. doi:10.1007/s12031-015-0685-4

    Article  CAS  PubMed  Google Scholar 

  26. Schmittgen TD, Livak KJ (2008) Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc 3:1101–1108

    Article  CAS  PubMed  Google Scholar 

  27. Fennell DA, Chacko A, Mutti L (2008) BCL-2 family regulation by the 20 S proteasome inhibitor bortezomib. Oncogene 27:1189–1197. doi:10.1038/sj.onc.1210744

    Article  CAS  PubMed  Google Scholar 

  28. Codony-Servat J, Tapia MA, Bosch M, Oliva C, Domingo-Domenech J, Mellado B, Rolfe M, Ross JS, Gascon P, Rovira A, Albanell J (2006) Differential cellular and molecular effects of bortezomib, a proteasome inhibitor, in human breast cancer cells. Mol Cancer Ther 5:665–675. doi:10.1158/1535-7163.MCT-05-0147

    Article  CAS  PubMed  Google Scholar 

  29. Kliková K, Štefaniková A, Pilchová I, Hatok J, Chudý P, Chudej J, Dobrota D, Račay P (2015) Differential impact of bortezomib on HL-60 and K562 cells. Gen Physiol Biophys 34:33–42. doi:10.4149/gpb_2014026

    Article  PubMed  Google Scholar 

  30. Stetler RA, Gan Y, Zhang W, Liou AK, Gao Y, Cao G, Chen J (2010) Heat shock proteins: cellular and molecular mechanisms in the central nervous system. Prog Neurobiol 92:184–211. doi:10.1016/j.pneurobio.2010.05.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Brignole C, Marimpietri D, Pastorino F, Nico B, Di Paolo D, Cioni M, Piccardi F, Cilli M, Pezzolo A, Corrias MV, Pistoia V, Ribatti D, Pagnan G, Ponzoni M (2006) Effect of bortezomib on human neuroblastoma cell growth, apoptosis, and angiogenesis. J Natl Cancer Inst 98:1142–1157. doi:10.1093/jnci/djj309

    Article  CAS  PubMed  Google Scholar 

  32. Corazzari M, Lovat PE, Armstrong JL, Fimia GM, Hill DS, Birch-Machin M, Redfern CP, Piacentini M (2007) Targeting homeostatic mechanisms of endoplasmic reticulum stress to increase susceptibility of cancer cells to fenretinide-induced apoptosis: the role of stress proteins ERdj5 and ERp57. Br J Cancer 96:1062–1071. doi:10.1038/sj.bjc.6603672

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Concannon CG, Koehler BF, Reimertz C, Murphy BM, Bonner C, Thurow N, Ward MW, Villunger A, Strasser A, Kögel D, Prehn JH (2007) Apoptosis induced by proteasome inhibition in cancer cells: predominant role of the p53/PUMA pathway. Oncogene 26:1681–1692. doi:10.1038/sj.onc.1209974

    Article  CAS  PubMed  Google Scholar 

  34. Baou M, Kohlhaas SL, Butterworth M, Vogler M, Dinsdale D, Walewska R, Majid A, Eldering E, Dyer MJ, Cohen GM (2010) Role of NOXA and its ubiquitination in proteasome inhibitor-induced apoptosis in chronic lymphocytic leukemia cells. Haematologica 95:1510–1518. doi:10.3324/haematol.2010.022368

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Armstrong JL, Flockhart R, Veal GJ, Lovat PE, Redfern CP (2010) Regulation of endoplasmic reticulum stress-induced cell death by ATF4 in neuroectodermal tumor cells. J Biol Chem 285:6091–6100. doi:10.1074/jbc.M109.014092

    Article  CAS  PubMed  Google Scholar 

  36. Hagenbuchner J, Ausserlechner MJ, Porto V, David R, Meister B, Bodner M, Villunger A, Geiger K, Obexer P (2010) The anti-apoptotic protein BCL2L1/Bcl-xL is neutralized by pro-apoptotic PMAIP1/Noxa in neuroblastoma, thereby determining bortezomib sensitivity independent of prosurvival MCL1 expression. J Biol Chem 285:6904–6912. doi:10.1074/jbc.M109.038331

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Chen HC, Kanai M, Inoue-Yamauchi A, Tu HC, Huang Y, Ren D, Kim H, Takeda S, Reyna DE, Chan PM, Ganesan YT, Liao CP, Gavathiotis E, Hsieh JJ, Cheng EH (2015) An interconnected hierarchical model of cell death regulation by the BCL-2 family. Nat Cell Biol 17:1270–1281. doi:10.1038/ncb3236

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Pfeiffer S, Anilkumar U, Chen G, Ramírez-Peinado S, Galindo-Moreno J, Muñoz-Pinedo C, Prehn JH (2014) Analysis of BH3-only proteins upregulated in response to oxygen/glucose deprivation in cortical neurons identifies Bmf but not Noxa as potential mediator of neuronal injury. Cell Death Dis 5:e1456. doi:10.1038/cddis.2014.426

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Pilchova I, Klacanova K, Chomova M, Tatarkova Z, Dobrota D, Racay P (2015) Possible contribution of proteins of Bcl-2 family in neuronal death following transient global brain ischemia. Cell Mol Neurobiol 35:23–31. doi:10.1007/s10571-014-0104-3

    Article  CAS  PubMed  Google Scholar 

  40. Endo H, Kamada H, Nito C, Nishi T, Chan PH (2006) Mitochondrial translocation of p53 mediates release of cytochrome c and hippocampal CA1 neuronal death after transient global cerebral ischemia in rats. J Neurosci 26:7974–7983

    Article  CAS  PubMed  Google Scholar 

  41. Germain M, Mathai JP, McBride HM, Shore GC (2005) Endoplasmic reticulum BIK initiates DRP1-regulated remodelling of mitochondrial cristae during apoptosis. EMBO J 24:1546–1556. doi:10.1038/sj.emboj.7600592

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Zhu H, Zhang L, Dong F, Guo W, Wu S, Teraishi F, Davis JJ, Chiao PJ, Fang B (2005) Bik/NBK accumulation correlates with apoptosis-induction by bortezomib (PS-341, Velcade) and other proteasome inhibitors. Oncogene 24:4993–4999. doi:10.1038/sj.onc.1208683

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Lopez J, Hesling C, Prudent J, Popgeorgiev N, Gadet R, Mikaelian I, Rimokh R, Gillet G, Gonzalo P (2012) Src tyrosine kinase inhibits apoptosis through the Erk1/2-dependent degradation of the death accelerator Bik. Cell Death Differ 19:1459–1469. doi:10.1038/cdd.2012.21

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Mathai JP, Germain M, Marcellus RC, Shore GC (2002) Induction and endoplasmic reticulum location of BIK/NBK in response to apoptotic signaling by E1A and p53. Oncogene 21:2534–2544. doi:10.1038/sj.onc.1205340

    Article  CAS  PubMed  Google Scholar 

  45. Yerlikaya A, Erin N (2008) Differential sensitivity of breast cancer and melanoma cells to proteasome inhibitor Velcade. Int J Mol Med 22:817–823

    CAS  PubMed  Google Scholar 

  46. Shi J, Zhao Y, Wang Y, Gao W, Ding J, Li P, Hu L, Shao F (2014) Inflammatory caspases are innate immune receptors for intracellular LPS. Nature 514:187–192. doi:10.1038/nature13683

    Article  CAS  PubMed  Google Scholar 

  47. Shalini S, Dorstyn L, Dawar S, Kumar S (2015) Old, new and emerging functions of caspases. Cell Death Differ 22:526–539

    Article  CAS  PubMed  Google Scholar 

  48. Yang HJ, Wang M, Wang L, Cheng BF, Lin XY, Feng ZW (2015) NF-κB regulates caspase-4 expression and sensitizes neuroblastoma cells to Fas-induced apoptosis. PLoS ONE 10:e0117953

    Article  PubMed  PubMed Central  Google Scholar 

  49. Kamada S, Washida M, Hasegawa J, Kusano H, Funahashi Y, Tsujimoto Y (1997) Involvement of caspase-4(-like) protease in Fas-mediated apoptotic pathway. Oncogene 15:285–290

    Article  CAS  PubMed  Google Scholar 

  50. Yamamuro A, Kishino T, Ohshima Y, Yoshioka Y, Kimura T, Kasai A, Maeda S (2011) Caspase-4 directly activates caspase-9 in endoplasmic reticulum stress-induced apoptosis in SH-SY5Y cells. J Pharmacol Sci 115:239–243

    Article  CAS  PubMed  Google Scholar 

  51. Oda T, Kosuge Y, Arakawa M, Ishige K, Ito Y (2008) Distinct mechanism of cell death is responsible for tunicamycin-induced ER stress in SK-N-SH and SH-SY5Y cells. Neurosci Res 60:29–39. doi:10.1016/j.neures.2007.09.005

    Article  CAS  PubMed  Google Scholar 

  52. Ridder DA, Schwaninger M (2009) NF-kappaB signaling in cerebral ischemia. Neuroscience 158:995–1006. doi:10.1016/j.neuroscience.2008.07.007

    Article  CAS  PubMed  Google Scholar 

  53. Chen D, Frezza M, Schmitt S, Kanwar J, Dou QP (2011) Bortezomib as the first proteasome inhibitor anticancer drug: current status and future perspectives. Curr Cancer Drug Targets 11:239–253

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Yin D, Zhou H, Kumagai T, Liu G, Ong JM, Black KL, Koeffler HP (2005) Proteasome inhibitor PS-341 causes cell growth arrest and apoptosis in human glioblastoma multiforme (GBM). Oncogene 24:344–354. doi:10.1038/sj.onc.1208225

    Article  CAS  PubMed  Google Scholar 

  55. Jane EP, Premkumar DR, Pollack IF (2011) Bortezomib sensitizes malignant human glioma cells to TRAIL, mediated by inhibition of the NF-{kappa}B signaling pathway. Mol Cancer Ther 10:198–208. doi:10.1158/1535-7163.MCT-10-0725

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Vlachostergios PJ, Hatzidaki E, Stathakis NE, Koukoulis GK, Papandreou CN (2013) Bortezomib downregulates MGMT expression in T98G glioblastoma cells. Cell Mol Neurobiol 33:313–318. doi:10.1007/s10571-013-9910-2

    Article  CAS  PubMed  Google Scholar 

  57. Baud V, Karin M (2009) Is NF-kappaB a good target for cancer therapy? Hopes and pitfalls. Nat Rev Drug Discov 8:33–40. doi:10.1038/nrd2781

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Deveraux QL, Reed JC (1999) IAP family proteins—suppressors of apoptosis. Genes Dev 13:239–252

    Article  CAS  PubMed  Google Scholar 

  59. Karin M, Cao Y, Greten FR, Li ZW (2002) NF-kappaB in cancer: from innocent bystander to major culprit. Nat Rev Cancer 2:301–310. doi:10.1038/nrc780

    Article  CAS  PubMed  Google Scholar 

  60. Inta I, Paxian S, Maegele I, Zhang W, Pizzi M, Spano P, Sarnico I, Muhammad S, Herrmann O, Inta D, Baumann B, Liou HC, Schmid RM, Schwaninger M (2006) Bim and Noxa are candidates to mediate the deleterious effect of the NF-kappa B subunit RelA in cerebral ischemia. J Neurosci 26:12896–12903. doi:10.1523/JNEUROSCI.3670-06.2006

    Article  CAS  PubMed  Google Scholar 

  61. Sarnico I, Lanzillotta A, Boroni F, Benarese M, Alghisi M, Schwaninger M, Inta I, Battistin L, Spano P, Pizzi M (2009) NF-kappaB p50/RelA and c-Rel-containing dimers: opposite regulators of neuron vulnerability to ischaemia. J Neurochem 108:475–485. doi:10.1111/j.1471-4159.2008.05783.x

    Article  CAS  PubMed  Google Scholar 

  62. Collins PE, Kiely PA, Carmody RJ (2014) Inhibition of transcription by B cell Leukemia 3 (Bcl-3) protein requires interaction with nuclear factor κB (NF-κB) p50. J Biol Chem 289:7059–7767. doi:10.1074/jbc.M114.551986

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Bence NF, Sampat RM, Kopito RR (2001) Impairment of the ubiquitin-proteasome system by protein aggregation. Science 292:1552–1555

    Article  CAS  PubMed  Google Scholar 

  64. Myeku N, Clelland CL, Emrani S, Kukushkin NV, Yu WH, Goldberg AL, Duff KE (2016) Tau-driven 26 S proteasome impairment and cognitive dysfunction can be prevented early in disease by activating cAMP-PKA signaling. Nat Med 22:46–53. doi:10.1038/nm.4011

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by the project Biomedical Center Martin (ITMS: 26220220187) co-financed from EU sources and by the project Creating a New Diagnostic Algorithm for Selected Cancer Diseases (ITMS: 26220220022) co-financed from EU sources and European Regional Development Fund. The authors are grateful to Dr. Martin Kolisek for his helpful comments and to Dr. Marian Grendar for his essential help with two-way ANOVA.

Author information

Authors and Affiliations

  1. Biomedical Center Martin JFM CU and Department of Medical Biochemistry JFM CU, Jessenius Faculty of Medicine in Martin (JFM CU), Comenius University in Bratislava, Mala Hora 4D, 03601, Martin, Slovak Republic

    Ivana Pilchova, Katarina Klacanova, Katarina Dibdiakova, Simona Saksonova, Andrea Stefanikova, Eva Vidomanova, Lucia Lichardusova, Jozef Hatok & Peter Racay

Authors
  1. Ivana Pilchova
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Katarina Klacanova
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Katarina Dibdiakova
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Simona Saksonova
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Andrea Stefanikova
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Eva Vidomanova
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Lucia Lichardusova
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jozef Hatok
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Peter Racay
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Peter Racay.

Ethics declarations

Conflict of interest

The authors declare no conflicts of interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pilchova, I., Klacanova, K., Dibdiakova, K. et al. Proteasome Stress Triggers Death of SH-SY5Y and T98G Cells via Different Cellular Mechanisms. Neurochem Res 42, 3170–3185 (2017). https://doi.org/10.1007/s11064-017-2355-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-017-2355-0

Keywords

Search

Navigation