N-Acetylcysteine Prevents the Increase in Spontaneous Oxidation of Dopamine During Monoamine Oxidase Inhibition in PC12 Cells

David S. Goldstein, Yunden Jinsmaa, Patti Sullivan, Yehonatan Sharabi

Research output: Contribution to journalArticlepeer-review

Abstract

The catecholaldehyde hypothesis for the pathogenesis of Parkinson’s disease proposes that the deaminated dopamine metabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL) is toxic to nigrostriatal dopaminergic neurons. Inhibiting monoamine oxidase (MAO) should therefore slow the disease progression; however, MAO inhibition increases spontaneous oxidation of dopamine, as indicated by increased 5-S-cysteinyl-dopamine (Cys-DA) levels, and the oxidation products may also be toxic. This study examined whether N-acetylcysteine (NAC), a precursor of the anti-oxidant glutathione, attenuates the increase in Cys-DA production during MAO inhibition. Rat pheochromocytoma PC12 cells were incubated with NAC, the MAO-B inhibitor selegiline, or both. Selegiline decreased DOPAL and increased Cys-DA levels (p < 0.0001 each). Co-incubation of NAC at pharmacologically relevant concentrations (1–10 µM) with selegiline (1 µM) attenuated or prevented the Cys-DA response to selegiline, without interfering with the selegiline-induced decrease in DOPAL production or inhibiting tyrosine hydroxylation. NAC therefore mitigates the increase in spontaneous oxidation of dopamine during MAO inhibition.

Original languageEnglish
Pages (from-to)3289-3295
Number of pages7
JournalNeurochemical Research
Volume42
Issue number11
DOIs
StatePublished - 1 Nov 2017

Keywords

  • Cysteinyl-dopamine
  • DOPAL
  • Monoamine oxidase
  • N-Acetylcysteine
  • Parkinson’s disease

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