Inhibition of brain monoamine oxidase activity by the generation of hydroxyl radicals: potential implications in relation to oxidative stress.
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.
Soto-Otero
R
R
Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad de Santiago de Compostela, Spain. bnsoto@usc.es
Méndez-Alvarez
E
E
Hermida-Ameijeiras
A
A
Sánchez-Sellero
I
I
Cruz-Landeira
A
A
Lamas
M L
ML
D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism; D001921:Brain / Q000201:enzymology*; D005296:Ferrous Compounds / Q000378:metabolism; D005470:Fluorometry; D017665:Hydroxyl Radical / Q000378:metabolism*; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley
D005296:Ferrous Compounds; D008996:Monoamine Oxidase Inhibitors; D017665:Hydroxyl Radical; D008995:Monoamine Oxidase; D001205:Ascorbic Acid