Increased dopamine peroxidation in postmortem Parkinsonian brain.
We have previously reported the presence, in human midbrain, of an enzymatic activity which catalyzes the formation of dopaminochrome from dopamine (DA) and hydrogen peroxide. Here, we report, for the first time, an increased DA peroxidizing activity in the midbrain and basal ganglia of autoptic Parkinsonian brains. The crude activity was determined spectrophotometrically in extracts of paraffin-embedded slices obtained from autopsied brain. No addition of substrate was necessary since endogenous substrates such as DA and hydrogen peroxide were present in the samples. In Parkinson's patients' midbrain, this activity was substantially increased compared to normal midbrain. Moreover, the DA peroxidizing activity, which was absent in basal ganglia of normal people, was detectable in all our Parkinson's patients. These observations suggest that a peroxidizing pathway of DA may be present in human brain. The increased peroxidizing activity in Parkinson's patients generates the toxic compound dopaminochrome which may play a role in the pathogenesis of this disease.
De Iuliis
Angela
A
Department of Diagnostics, University of Padua, Viale G. Colombo 3, Italy. angela.deiuliis@unipd.it
Burlina
Alessandro P
AP
Boschetto
Roberta
R
Zambenedetti
Pamela
P
Arslan
Paola
P
Galzigna
Lauro
L
D000368:Aged; D000369:Aged, 80 and over; D001479:Basal Ganglia / Q000378:metabolism; D001921:Brain / Q000201:enzymology / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D006358:Hot Temperature; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D045563:Indolequinones; D007211:Indoles / Q000378:metabolism; D008297:Male; D008636:Mesencephalon / Q000378:metabolism; D008875:Middle Aged; D010084:Oxidation-Reduction; D010300:Parkinson Disease / Q000201:enzymology / Q000209:etiology / Q000378:metabolism*; D011180:Postmortem Changes
D045563:Indolequinones; D007211:Indoles; C091584:aminochrome 1; D006861:Hydrogen Peroxide; D004298:Dopamine