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N-Acetylcysteine Prevents the Increase in Spontaneous Oxidation of Dopamine During Monoamine Oxidase Inhibition in PC12 Cells.
- Source :
-
Neurochemical Research . Nov2017, Vol. 42 Issue 11, p3289-3295. 7p. - Publication Year :
- 2017
-
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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 03643190
- Volume :
- 42
- Issue :
- 11
- Database :
- Academic Search Index
- Journal :
- Neurochemical Research
- Publication Type :
- Academic Journal
- Accession number :
- 125825059
- Full Text :
- https://doi.org/10.1007/s11064-017-2371-0