A comparative study of proteasomal inhibition and apoptosis induced in N27 mesencephalic cells by dopamine and MG132

Khan Shoeb Zafar, Salmaan H. Inayat-Hussain, David Ross

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Dopamine (DA) and its metabolites have been implicated in the pathogenesis of Parkinson's disease. DA can produce reactive-oxygen species and DA-derived quinones such as aminochrome can induce proteasomal inhibition. We therefore examined the ability of DA and MG132 to induce apoptosis and proteasomal inhibition in N27 rat dopaminergic cells. DA (0-500 μmol/L, 0-24 h) and MG132 (0-5 μmol/L, 0-24 h) treated N27 cells resulted in time- and concentration-dependent apoptosis. To better define DA and MG132-induced apoptosis, the activation of initiator caspases 2 and caspase 9 and the executioner caspase 3 was investigated. Activation of caspase 2, caspase 9, and caspase 3 occurred early and prior to cell death. In addition, N-acetylcysteine (NAC) blocked DA but not MG132-induced apoptosis and mitochondrial membrane potential loss. NAC can react with both reactive-oxygen and quinoid metabolites and its inhibitory activity suggests a role for reactive species in DA-induced apoptosis. Proteasomal inhibition was detected after DA treatment in N27 cells which occurred prior to cell death and was abrogated by NAC. Our results implicate DA-derived reactive species in proteasomal inhibition and caspase-dependent apoptosis in N27 cells. The ability of endogenous DA-derived metabolites to induce proteasomal inhibition and apoptosis may contribute to the selective loss of dopaminergic neurons in Parkinson's disease.

Original languageEnglish
Pages (from-to)913-921
Number of pages9
JournalJournal of Neurochemistry
Volume102
Issue number3
DOIs
Publication statusPublished - Aug 2007
Externally publishedYes

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Dopamine
Apoptosis
Acetylcysteine
Caspase 2
Metabolites
Caspase 9
Cell death
Caspase 3
Parkinson Disease
Cell Death
Initiator Caspases
benzyloxycarbonylleucyl-leucyl-leucine aldehyde
Chemical activation
Mitochondrial Membrane Potential
Quinones
Dopaminergic Neurons
Caspases
Reactive Oxygen Species
Neurons
Rats

Keywords

  • Aminochrome
  • Apoptosis
  • Dopamine
  • MG132
  • Parkinson's disease
  • Proteasomal inhibition
  • Quinones

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

A comparative study of proteasomal inhibition and apoptosis induced in N27 mesencephalic cells by dopamine and MG132. / Zafar, Khan Shoeb; Inayat-Hussain, Salmaan H.; Ross, David.

In: Journal of Neurochemistry, Vol. 102, No. 3, 08.2007, p. 913-921.

Research output: Contribution to journalArticle

Zafar, Khan Shoeb ; Inayat-Hussain, Salmaan H. ; Ross, David. / A comparative study of proteasomal inhibition and apoptosis induced in N27 mesencephalic cells by dopamine and MG132. In: Journal of Neurochemistry. 2007 ; Vol. 102, No. 3. pp. 913-921.
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