Terminally differentiated SH-SY5Y cells provide a model system for studying neuroprotective effects of dopamine agonists

Steven P. Presgraves, Tariq Ahmed, Sabine Borwege, Jeffrey N. Joyce

Research output: Contribution to journalArticle

148 Citations (Scopus)

Abstract

We characterized undifferentiated (UN) and three differentiation conditions of the SH-SY5Y neuroblastoma cell line for phenotypic markers of dopaminergic cells, sensitivity to the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridinium ion (MPP), the requirement to utilize the dopamine (DA) transporter (DAT) for MPP toxicity, and the neuroprotective effects of pramipexole. Cells were differentiated with retinoic acid (RA), 12-O-tetradecanoly-phorbol-13-acetate (TPA), and RA followed by TPA (RA/TPA). RA/TPA treated cells exhibited the highest levels of tyrosine hydroxylase and DAT but lower levels of vesicular monoamine transporter. The kinetics of [ 3H]DA uptake and [ 3H]MPP uptake to DAT in RA/TPA differentiated cells were similar to that of rat and mouse caudate-putamen synaptosomes. RA/TPA differentiated cells evidenced high sensitivity to the neurotoxic effects of MPP (0.03 to 3.0 mM), and the neurotoxic effects of MPP were blocked with the DAT inhibitor 1-(2-[bis(4-fluorophenyl)methoxy]ethyl)-4-(3-phenylpropyl) piperazine (GBR 12909). DA-induced cell death was not more sensitive in RA vs RA/TPA differentiated cells and was not inhibited by transporter inhibitors. RA/TPA differentiated cells exhibited 3- fold and 6-fold higher levels, respectively, of DA D 2 and D 3 receptors than UN or RA differentiated cells. Pretreatment with pramipexole was protective against MPP in the RA/TPA differentiated cells but not in undifferentiated or RA differentiated cells. The neuroprotective effect of pramipexole was concentration-dependent and dopamine D 2/D 3 receptor dependent. In contrast, protection by pramipexole against DA was not DA receptor dependent. Further characterization of the neuroprotective effects of DA agonists in this model system can provide unique information about DA receptor dependent and independent mechanisms of neuroprotection.

Original languageEnglish
Pages (from-to)579-598
Number of pages20
JournalNeurotoxicity Research
Volume5
Issue number8
DOIs
Publication statusPublished - 2003
Externally publishedYes

Fingerprint

Dopamine Agonists
Neuroprotective Agents
Tretinoin
Acetates
Dopamine
Dopamine Receptors
Vesicular Monoamine Transport Proteins
Cells
phorbol
Dopamine Plasma Membrane Transport Proteins
Synaptosomes
Putamen
Neurotoxins
Tyrosine 3-Monooxygenase
Cell death
Neuroblastoma
Toxicity
Rats
Cell Death
Ions

Keywords

  • D Receptor
  • D Receptor
  • Dopamine transporter
  • MPP
  • Parkinson's disease
  • Pramipexole

ASJC Scopus subject areas

  • Neuroscience(all)
  • Toxicology

Cite this

Terminally differentiated SH-SY5Y cells provide a model system for studying neuroprotective effects of dopamine agonists. / Presgraves, Steven P.; Ahmed, Tariq; Borwege, Sabine; Joyce, Jeffrey N.

In: Neurotoxicity Research, Vol. 5, No. 8, 2003, p. 579-598.

Research output: Contribution to journalArticle

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