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Inhibition of brain monoamine oxidase activity by the generation of hydroxyl radicals: potential implications in
R Soto-Otero1, E Méndez-Alvarez, A Hermida-Ameijeiras
1Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad de Santiago de Compostela, Spain. bnsoto@usc.es
Abstract:
Monoamine oxidase (MAO) is an enzyme involved in brain catabolism of monoamine neurotransmitters whose oxidative deamination results in the production of hydrogen peroxide. It has been documented that hydrogen peroxide derived from MAO activity represents a special source of oxidative stress in the brain. In this study we investigated the potential effects of the production of hydroxyl radicals (*OH) on MAO-A and MAO-B activities using mitochondrial preparations obtained from rat brain. Ascorbic acid (100 microM) and Fe2+ (0.2, 0.4, 0.8, and 1.6 microM) were used to induce the production of *OH. Results showed that the generation of *OH significantly reduced both MAO-A (85-53%) and MAO-B (77-39%) activities, exhibiting a linear correlation between both MAO-A and MAO-B activities and the amount of *OH produced. The reported inhibition was found to be irreversible for both MAO-A and MAO-B. Assuming the proven contribution of MAO activity to brain oxidative stress, this inhibition appears to reduce this contribution when an overproduction of *OH occurs.
Insights
Hydroxyl radicals (*OH) irreversibly inhibit monoamine oxidase (MAO) enzymes A and B in rat brains. This finding suggests MAO activity
Area of Science:
- Neuroscience
- Biochemistry
- Enzymology
Background:
- Monoamine oxidase (MAO) catabolizes neurotransmitters, producing hydrogen peroxide.
- MAO-derived hydrogen peroxide contributes to oxidative stress in the brain.
Purpose of the Study:
- To investigate the impact of hydroxyl radical (*OH) production on MAO-A and MAO-B activities.
- To determine if *OH generation affects MAO enzyme function in rat brain mitochondria.
Main Methods:
- Utilized rat brain mitochondrial preparations.
- Induced *OH production using ascorbic acid and varying concentrations of Fe2+.
- Assessed the effects of *OH on MAO-A and MAO-B activities.
Main Results:
- Hydroxyl radical generation significantly reduced both MAO-A (53-85%) and MAO-B (39-77%) activities.
- A linear correlation was observed between *OH levels and the inhibition of both MAO-A and MAO-B.
- The observed inhibition of MAO-A and MAO-B by *OH was irreversible.
Conclusions:
- Hydroxyl radicals exert an irreversible inhibitory effect on MAO-A and MAO-B.
- This inhibition may mitigate the contribution of MAO activity to brain oxidative stress under conditions of *OH overproduction.
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