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Cell Stress and Chaperones

, Volume 13, Issue 1, pp 73–84 | Cite as

Changes in the regulation of heat shock gene expression in neuronal cell differentiation

  • Jay Oza
  • Jingxian Yang
  • Kuang Yu Chen
  • Alice Y.-C. Liu
Original Paper

Abstract

Neuronal differentiation of the NG108-15 neuroblastoma–glioma hybrid cells is accompanied by a marked attenuation in the heat shock induction of the Hsp70-firefly luciferase reporter gene activity. Analysis of the amount and activation of heat shock factor 1, induction of mRNAhsp, and the synthesis and accumulation of heat shock proteins (HSPs) in the undifferentiated and differentiated cells suggest a transcriptional mechanism for this attenuation. Concomitant with a decreased induction of the 72-kDa Hsp70 protein in the differentiated cells, there is an increased abundance of the constitutive 73-kDa Hsc70, a protein known to function in vesicle trafficking. Assessment of sensitivity of the undifferentiated and differentiated cells against stress-induced cell death reveals a significantly greater vulnerability of the differentiated cells toward the cytotoxic effects of arsenite and glutamate/glycine. This study shows that changes in regulation of the HSP and HSC proteins are components of the neuronal cell differentiation program and that the attenuated induction of HSPs likely contributes to neuronal vulnerability whereas the increased expression of Hsc70 likely has a role in neural-specific functions.

Keywords

Heat shock gene expression Neuronal cell differentiation Heat shock protein 

Notes

Acknowledgement

We are grateful to Dr. Mark Plummer of the Department of Cell Biology and Neuroscience for providing us with the rat embryonic hippocampal neuron culture (Magby et al. 2006). We thank Dr. Gutian Xiao for the Hsp70 knockout MEF. This work was supported in part by grants from the NSF (MCB0240009) and NJ Commission on Spinal Cord Research (05-3037-SCR-E-0).

References

  1. Akbar MT, Lundberg AMC, Liu K et al (2003) The neuroprotective effects of heat shock protein 27 overexpression in transgenic animals against kainate-induced seizures and hippocampal cell death. J Biol Chem 278:19956–19965PubMedCrossRefGoogle Scholar
  2. Amin V, Cumming DVE, Latchman DS (1996) Over-expression of heat shock protein 70 protects neuronal cells against both thermal and ischaemic stress but with different efficiencies. Neuro Lett 206:45–48CrossRefGoogle Scholar
  3. Batulan Z, Shinder GA, Minotti, S, He BP, Doroudchi MM, Nalbantoglu J, Strong, MJ, Durham HD (2003) High threshold for induction of the stress response in motor neurons is associated with failure to activate HSF1. J Neuroscience 23:5789–5798Google Scholar
  4. Beczkowska IW, Buck J, Inturrisi CE (1996) Retinoic acid-induced increase in delta-opioid receptor and N-methyl-d-aspartate receptor mRNA levels in neuroblastoma × glioma (NG108-15) cells. Brain Res Bull 39:193–199PubMedCrossRefGoogle Scholar
  5. Beczkowska IW, Gracy KN, Pickel VM, Inturrisi CE (1997) Detection of delta opiod receptor and N-methyl-d-aspartate receptor like immunoreactivity in retinoic acid-differentiated neuroblastoma × glioma (NG108-15) cells. J Neurosci Res 47:83–89PubMedCrossRefGoogle Scholar
  6. Benn SC, Brown RH (2004) Putting the heat on ALS. Nat Med 10:345–347PubMedCrossRefGoogle Scholar
  7. Bonini NM (2002) Chaperoning brain degeneration. Proc Natl Acad Sci U S A 99:16407–16411PubMedCrossRefGoogle Scholar
  8. Chen S, Brown IR (2007) Neuronal expression of constitutive heat shock proteins: implications for neurodegenerative diseases. Cell Stress Chaperones 12:51–58PubMedCrossRefGoogle Scholar
  9. Chiti Z, Teschemacher AG (2007) Exocytosis of norepinephrine at axon varicosities and neuronal cell bodies in the rat brain. FASEB J 21:1–11CrossRefGoogle Scholar
  10. Choi HS, Li B, Lin Z, Huang LE, Liu AY-C (1991) cAMP- and cAMP-dependent protein kinase regulate the human heat shock protein 70 gene promoter activity. J Biol Chem 266:11858–11865PubMedGoogle Scholar
  11. Cooper RL, Marin L, Atwood HL (1995) Synaptic differentiation of a single motor neuron: conjoint definition of transmitter release, presynaptic calcium signals, and ultrastructure. J Neurosci 15:4209–4222PubMedGoogle Scholar
  12. Dwyer DS, Liu Y, Miao S, Bradley RJ (1996) Neuronal differentiation in PC12 cells is accompanied by diminished inducibility of Hsp70 and HPS 60 in response to heat and ethanol. Neurochemical Res 21:659–666CrossRefGoogle Scholar
  13. Feige U, Morimoto RI, Yahara I, Polla BS (eds) (1996) Stress-inducible cellular responses. Birkhauser, BaselGoogle Scholar
  14. Gabai VL, Sherman MY (2002) Interplay between molecular chaperones and signaling pathways in survival of heat shock. J Appl Physiol 92:1742–1748Google Scholar
  15. Guzhova I, Kislyakova K, Moskaliova O, Friedlanskaya I, Tytell M, Cheetham M, Margulis V (2001) In vitro studies show that Hsp70 can be released by glia and that exogenous Hsp70 can enhance neuronal stress tolerance. Brain Res 914:66–73PubMedCrossRefGoogle Scholar
  16. Hatayama T, Takahashi H, Yamagishi N (1997) Reduced induction of Hsp70 in PC12 cells during neuronal differentiation. J Biochem 122:904–910PubMedGoogle Scholar
  17. Hendrick JP, Hartl FU (1995) The role of molecular chaperones in protein folding. FEBS J 9:1559–1569Google Scholar
  18. Hickey E, Brandon SE, Potter R, Stein G, Stein J, Weber LA (1986) Sequence and organization of genes encoding the human 27 kDa heat shock protein. Nucleic Acids Res 14:4127–4145PubMedCrossRefGoogle Scholar
  19. Huang LE, Zhang H, Bae SW, Liu AY-C (1994) Thiol reducing reagents inhibit the heat shock response: involvement of a redox mechanism in the heat shock signal transduction pathway. J Biol Chem 269:30718–30725PubMedGoogle Scholar
  20. Khalil S, Luciano J, Chen W, Liu, AYC (2006) Dynamic regulation and involvement of the heat shock transcriptional response in arsenic carcinogenesis. J Cell Physiol 207:562–569PubMedCrossRefGoogle Scholar
  21. Landsbury PT (2004) Back to the future: the ‘old-fashioned’ way to new medications for neurodegeneration. Nat Rev Neurosci 5:S51–S57CrossRefGoogle Scholar
  22. Lis J, Wu C (1993) Protein traffic on the heat shock promoter: parking, stalling, and trucking along. Cell 74:1–4PubMedCrossRefGoogle Scholar
  23. Macieira-Coelho A (1995) The last mitoses of the human fibroblast proliferative life span, physiopathologic implications. Mech Ageing Dev 82:91–104PubMedCrossRefGoogle Scholar
  24. Magby JP, Bi C, Chen ZY, Lee FS, Plummer MR (2006) Single-cell characterization of retrograde signaling by brain-derived neurotrophic factor. J Neuroscience 26:13531–13536CrossRefGoogle Scholar
  25. Mandell JW, MacLeish PR, Townes-Anderson E (1993) Process outgrowth and synaptic varicosity formation by adult photoreceptors in vitro. J Neuroscience 13:3533–3548Google Scholar
  26. Manzerra P, Brown IR (1996) The neuronal stress response: nuclear translocation of heat shock proteins as an indicator of hyperthermic stress. Exp Cell Res 229:35–47PubMedCrossRefGoogle Scholar
  27. Marcuccilli CJ, Mathur SK, Morimoto RI, Miller RJ (1996) Regulatory differences in the stress response of hippocampal neurons and glial cells after heat shock. J Neuroscience 16:478–485Google Scholar
  28. Meyer SA, Lin A, Liu AYC (1988) Neurite extension and increased expression of R1 cyclic AMP-binding protein in ouabain-resistant neuroblastoma mutants. J Neurochem 51:950–959PubMedCrossRefGoogle Scholar
  29. Michaelis EK (1998) Molecular biology of glutamate receptors in the central nervous system and their role in excitotoxicity, oxidative stress and aging. Prog Neurobiol 54:369–415PubMedCrossRefGoogle Scholar
  30. Morimoto RI (1993) Cells in stress: transcriptional activation of heat shock genes. Science 259:1409–1410PubMedCrossRefGoogle Scholar
  31. Morimoto RI (1998) Regulation of the heat shock transcriptional response: cross talk between a family of heat shock factors, molecular chaperones, and negative regulators. Genes Dev 12:378–3796CrossRefGoogle Scholar
  32. Morimoto RI (2006) Stress, aging, and neurodegenerative disease. N Eng J Med 355:2254–2255CrossRefGoogle Scholar
  33. Morimoto RI, Tissieres A, Georgopoulos C (eds) (1994) The biology of heat shock proteins and molecular chaperones. Cold Spring Harbor Laboratory Press, New YorkGoogle Scholar
  34. Mosser DD, Carbon AE, Bourget L, Merlin AB, Sherman MY, Morimoto RI, Massie B (2000) The chaperone function of Hsp70 is required for protection against stress-induced apoptosis. Mol Cell Biol 20:7146–7159PubMedCrossRefGoogle Scholar
  35. Muchowski PJ (2002) Protein misfolding, amyloid formation, and neurodegeneration: a critical role for molecular chaperones? Neuron 35:9–12PubMedCrossRefGoogle Scholar
  36. Muchowski PJ, Wacker JL (2005) Modulation of neurodegeneration by molecular chaperones. Nat Rev Neurosci 6:11–22PubMedCrossRefGoogle Scholar
  37. Nelson P, Christian C, Nirenberg M (1976) Synapse formation between clonal neuroblastoma × glioma hybrid cells and striated muscle cells. Proc Natl Acad Sci U S A 73:123–127PubMedCrossRefGoogle Scholar
  38. Nirenberg M, Wilson S, Higashida H et al (1983) Synapse formation by neuroblastoma hybrid cells. Cold Spring Harbor Symp Quant Biol 48:707–715PubMedGoogle Scholar
  39. Nirenberg M, Wilson S, Higashida H et al (1984) Modulation of synapse formation by cyclic adenosine monophsophate. Science 222:794–799CrossRefGoogle Scholar
  40. Nishimura RN, Dwyer BE (1996) Evidence for different mechanisms of induction of Hsp70i: a comparison of cultured rat cortical neurons with astrocytes. Mol Brain Res 36:227–239PubMedCrossRefGoogle Scholar
  41. Pizzi M, Boroni F, Bianschetti A et al (2002) Expression of functional NR1/NR2B-type NMDA receptors in neuronally differentiated SK–N–SH human cell line. Euro J Neuro Sci 16:2342–2350CrossRefGoogle Scholar
  42. Rordorf G, Koroshetz WJ, Bonventre JV (1991) Heat shock protects cultured neurons from glutamate toxicity. Neuron 7:1043–1051PubMedCrossRefGoogle Scholar
  43. Schubert D, Piasecki D (2001) Oxidative glutamate toxicity can be a component of the excitotoxicity cascade. J Neuroscience 21:7455–7462Google Scholar
  44. Sharp FR, Massa SM, Swanson RA (1999) Heat shock protein protection. Trends in Neuroscience 22:97–99CrossRefGoogle Scholar
  45. Sherman MY, Goldberg AL (2001) Cellular defenses against unfolded proteins: A cell biologist thinks about neurodegenerative diseases. Neuron 29:15–32PubMedCrossRefGoogle Scholar
  46. Tytell M, Greenberg SG, Lasek RJ (1996) Heat shock-like protein is transferred from glia to axon. Brain Res 363:161–164CrossRefGoogle Scholar
  47. Varju P, Schlett K, Eisel U, Madarász E (2001) Schedule of NMDA receptor subunit expression and functional channel formation in the course of in vitro-induced neurogeneisis. J Neurochem 77:1444–1456PubMedCrossRefGoogle Scholar
  48. Voellmy R (1994) Transduction of the stress signal and mechanisms of transcriptional regulation of heat shock/stress protein gene expression in higher eukaryotes. Critical Rev Eukaryot Gene Expr 4:357–401Google Scholar
  49. Waxman EA, Lynch DR (2005) N-methyl-d-aspartate receptor subtypes: multiple roles in excitotoxicity and neurological disease. Neuroscientist 11:37–49PubMedCrossRefGoogle Scholar
  50. Welch WJ, Gambetti P (1998) Chaperoning brain diseases. Nature 392:23PubMedCrossRefGoogle Scholar
  51. Westerheide SD, Morimoto RI (2005) Heat shock response modulators as therapeutic tools for diseases of protein conformation. J Biol Chem 280:33097–33100PubMedCrossRefGoogle Scholar
  52. Yanagida Y, Mizuno A, Motegi T, Kobatake E, Aizawa M (2000) Electrically stimulated induction of hsp 70 gene expression in mouse astroglia and fibroblast cells. J Biotechnology 79:53–61CrossRefGoogle Scholar
  53. Yenari MA, Fink SL, Sun GH et al (1998) Gene therapy with HSP72 is neuroprotective in rat models of stroke and epilepsy. Ann Neurol 44(4):584–591PubMedCrossRefGoogle Scholar
  54. Yenari MA, Giffard RG, Sapolsky RM, Steinberg GK (1999) The neuroprotective potential of heat shock protein 70 (Hsp70). Mol Med Today 5(12):525–531PubMedCrossRefGoogle Scholar
  55. Young JC, Barral JM, Hartl FU (2003) More than folding: localized function of cytosolic chaperones. Trends Biochem Sci 28:541–547PubMedCrossRefGoogle Scholar
  56. Zinsmaier KE, Bronk P (2001) Molecular chaperones and the regulation of neurotransmitter exocytosis. Biochem Pharmacol 2001(62):1–11CrossRefGoogle Scholar

Copyright information

© Cell Stress Society International 2008

Authors and Affiliations

  • Jay Oza
    • 1
  • Jingxian Yang
    • 1
  • Kuang Yu Chen
    • 2
  • Alice Y.-C. Liu
    • 1
  1. 1.Department of Cell Biology and Neuroscience, Division of Life SciencesRutgers State University of New JerseyPiscatawayUSA
  2. 2.Department of Chemistry and Chemical BiologyRutgers State University of New JerseyPiscatawayUSA

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