Skip to main content
SpringerLink
Log in

Neuroprotective effects of nicotine against salsolinol-induced cytotoxicity: Implications for parkinson’s disease

  • Published:
Neurotoxicity Research Aims and scope Submit manuscript

Abstract

Parkinson’s disease is associated with degeneration of dopaminergic cell bodies in the substantia nigra. It has been suggested that salsolinol, an endogenous metabolite of dopamine, may be involved in this process. An inverse relationship between Parkinson’s disease and smoking (nicotine intake) has been observed in epidemiological studies. Moreover, neuroprotective effects of nicotine in various experimental models have been observed. In this study we sought to determine whether salsolinol-induced cytotoxicity in SH-SY5Y human neuroblastoma cells, a cloned cell line which expresses dopaminergic activity, could also be prevented by nicotine pretreatment, and if so, which nicotinic receptors may mediate the actions of nicotine. Exposure of SH-SY5Y cells to 0.8 mM salsolinol for 24 hours resulted in approximately 80% cell death as determined by 3,[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) assay. Pretreatment of cells with 0.1 mM nicotine resulted in inhibition of salsolinol-induced cytotoxicity. The effects of nicotine were blocked by mecamylamine, a non-selective nicotinic antagonist as well as conotoxins with selective antagonism against alpha3-containing nicotinic receptor subunits. The effects of nicotine were not affected by dihydro-beta-erythroidine or methyl-lycaconitine, selective antagonists against alpha4-beta2 or alpha7 nicotinic receptors, respectively. It is suggested that selective nicotinic agonists may be of therapeutic potential in at least a subpopulation of Parkinsonian patients.

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

Similar content being viewed by others

References

  • Dajas-Bailador FA, L Soliakov and S Wonnacott (2002) Nicotine activates the extracellular signal-regulated kinase I/2 via the α7 nicotinic acetylcholine receptor and protein kinase A, in SH-SY5Y cells and hippocampal neurones.J. Neurochem. 80, 520–530.

    Article  PubMed  CAS  Google Scholar 

  • Dowell C, BM Olivera, JE Garrett, ST Staheli, M Watkins, A Kuryatov, D Yoshikami, JM Lindstrom and JM McIntosh (2003) α-Conotoxin PIA is selective for α6 subunit-containing nicotinic acetylcholine receptors.J. Neurosci. 23, 8445–8562.

    PubMed  CAS  Google Scholar 

  • Gorell JM, BA Rybicki, CC Johnson and EL Peterson (1999) Smoking and Parkinson’s disease: a dose-response relationship.Neurology 52, 115–119.

    PubMed  CAS  Google Scholar 

  • Guan ZZ, WF Yu and A Nordberg (2003) Dual effects of nicotine on oxidative stress and neuroprotection in PC12 cells.Neurochem. Intl. 43, 243–249.

    Article  CAS  Google Scholar 

  • Hejmadi MV, F Dajas-Bailador, SM Barns, B Jones and S Wonnacott (2003) Neuroprotection by nicotine against hypoxia-induced apoptosis in cortical cultures involves activation of multiple nicotinic acetylcholine receptor subtypes.Mol. Cell. Neurosci. 24, 779–786.

    Article  PubMed  CAS  Google Scholar 

  • Hernan MA, B Takkouche, F Caamano-Isorna and JJ Gestal-Otero (2002) A meta-analysis of coffee drinking, cigarette smoking, and the risk of Parkinson’s disease. Ann.Neurol. 52, 276–284.

    Google Scholar 

  • Kihara T, S Shimohama, M Urushitani, H Sawada, J Kimura, T Kume, T Maeda and A Akaike (1998) Stimulation of alpha4 beta2 nicotinic acetylcholine receptors inhibits beta-amyloid toxicity.Brain Res. 792, 331–334.

    Article  PubMed  CAS  Google Scholar 

  • Liu Q and B Zhao (2004) Nicotine attenuates beta-amyloid peptide-induced neurotoxicity, free radical and calcium accumulation in hippocampal neuronal cultures.Br. J. Pharmacol. 141, 746–754.

    Article  PubMed  CAS  Google Scholar 

  • Lukas RJ, SA Norman and L Lucero (1993) Characterization of nicotinic acetylcholine receptors expressed by cells of the SH-SY5Y human neuroblastoma clone line.Mol. Cell. Neurosci. 4, 1–12.

    Article  CAS  Google Scholar 

  • Luo S, JM Kulak, GE Cartier, RB Jacobson, D Yoshikami, BM Olivera and JM McIntosh (1998) α-Conotoxin AuIB selectively blocks α3β4 nicotinic acetylcholine receptors and nicotine-evoked norepinephrine release.J. Neurosci. 18, 8571–8579.

    PubMed  CAS  Google Scholar 

  • Maruyama W, H Yi, T Takahashi, S Shimazu, H Ohde, F Yoneda, K Iwasa and M Naoi (2004) neuroprotective function of R-(-)-1-(benzufuran-2-yl)-2-propylaminopentane, [R-(-)-BPAP], against apoptosis induced byN-methyl(R)salsolinol, an endogenous dopaminergic neurotoxin, in human dopaminergic neuroblastoma SH-SY5Y cells.Life Sci. 75, 107–117.

    Article  PubMed  CAS  Google Scholar 

  • Naoi M, W Maruyama and GM Nagy (2004) Dopamine-derived salsolinol derivatives as endogenous monoamine oxidase inhibitors: occurrence, metabolism and function in human brains.Neurotox. 25, 193–204.

    Article  CAS  Google Scholar 

  • Nicke A, S Wonnacott and RJ Lewis (2004) α-Conotoxins as tools for the elucidation of structure and function of neuronal nicotinic acetylcholine receptor subtypes.Eur. J. Biochem. 271, 2305–2319.

    Article  PubMed  CAS  Google Scholar 

  • Parain K, C Hapdey, E Rousselet, V Marchand, B Dumery and EC Hirsch (2003) Cigarette smoke and nicotine protect dopaminergic neurons against the 1-methyl-4-phenyl-1,2,3,6-tetrahydro-pyridine Parkinsonian toxin.Brain Res. 984, 224–232.

    Article  PubMed  CAS  Google Scholar 

  • Quik M, T Bordia and JM McIntosh (2004) Loss of α-conotoxin MII- and A85380-sensitive nicotinic receptors in Parkinson’s disease striatum.J. Neurochem. 88, 668–679.

    Article  PubMed  CAS  Google Scholar 

  • Stevens TR, SR Krueger, RM Fitzsimonds and MR Picciotto (2003) Neuroprotection by nicotine in mouse primary cortical cultures involves activation of calcineurin and l-type calcium channel inactivation.J. Neurosci. 23, 10093–10099.

    PubMed  CAS  Google Scholar 

  • Storch A, A Kaftan, K Burkhardt and J Schwarz (2000) 1-methyl-6, 7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (salsolinol) is toxic to dopaminergic neuroblastoma SH-SY5Y cells via impairment of cellular energy metabolism.Brain Res. 855, 67–75.

    Article  PubMed  CAS  Google Scholar 

  • Storch A, S Ott, Y Hwang, R Ortmann, A Hein, S Frenzel, K Matsubara, S Ohta, H Wolf and J Schwarz (2002) Selective dopaminergic neurotoxicity of isoquinoline derivatives related to Parkinson’s disease: studies using heterologous expression systems of the dopamine transporter.Biochem. Pharmacol. 63, 909–920.

    Article  PubMed  CAS  Google Scholar 

  • Tizabi Y, M Al-Namaeh, KF Manaye and RE Taylor (2003) Protective effects of nicotine on ethanol-induced toxicity in cultured cerebellar granule cells.Neurotoxicity Res. 5, 315–322.

    Article  Google Scholar 

  • Tizabi Y, KF Manaye, DT Smoot and RE Taylor (2004) Nicotine inhibits ethanol-induced toxicity in cultured cerebral cortical cells.Neurotoxicity Res. 6, 311–316.

    Google Scholar 

  • Tizabi Y, KF Manaye and RE Taylor (2005) Nicotine blocks ethanol-induced apoptosis in primary cultures of rat cerebral cortical and cerebellar granule cells.Neurotoxicity Res. 7, 319–322.

    CAS  Google Scholar 

  • Wirdefeldt K, M Gatz, Y Pawitan and NL Pedersen (2005) Risk and protective factors for Parkinson’s disease: a study in Swedish twins.Ann. Neurol. 57, 27–33.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacology, Howard University, 20059, Washington, DC, USA

    Robert L. Copeland, Yaminah A. Leggett, Robert E. Taylor & Yousef Tizabi

  2. Department of Microbiology, College of Medicine, Howard University, 20059, Washington, DC, USA

    Yasmine M. Kanaan

Authors
  1. Robert L. Copeland
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yaminah A. Leggett
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yasmine M. Kanaan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Robert E. Taylor
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yousef Tizabi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yousef Tizabi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Copeland, R.L., Leggett, Y.A., Kanaan, Y.M. et al. Neuroprotective effects of nicotine against salsolinol-induced cytotoxicity: Implications for parkinson’s disease. neurotox res 8, 289–293 (2005). https://doi.org/10.1007/BF03033982

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03033982

Keywords

Search

Navigation