Inhibition of catalase in mesencephalic cultures by L-DOPA and dopamine.
Catalase activity in cell cultures of fetal rat mesencephalon was decreased by 42 and 50%, respectively, after exposure to L-3,4-dihydroxyphenylalanine (L-DOPA, 100 microM) or dopamine (100 microM) for 48 h. Catalase activity was also decreased 21% by 10 microM hydroquinone. Ascorbic acid (200 microM), an agent that suppresses the autoxidation of L-DOPA and dopamine, blocked the anti-catalase effect of L-DOPA, but not that of dopamine. Inhibitors of the A and B forms of monoamine oxidase (20 microM clorgyline plus 20 microM pargyline) had no effect on the anti-catalase action of either L-DOPA or dopamine. The latter results suggest that products of the oxidative deamination of dopamine by monoamine oxidase are not involved in the suppression of catalase activity. However, autoxidation reactions of L-DOPA may play a role since ascorbate suppressed the anti-catalase effect of L-DOPA. On the contrary, the basis for the failure of ascorbate to similarly block the anti-catalase effect of dopamine is uncertain. L-DOPA and dopamine (25 microM) also inhibited crystalline catalase in solution after incubation for 1 h at neutral pH (40-50% inhibition). Inhibition was blocked by 0.45 M ethanol, indicating a need for autoxidation and the formation of compound II, which is an enzymatically inactive form of catalase. The ability to model the enzyme inhibition in purely chemical experiments indicates a probable mechanism for loss of enzymatic activity in cell cultures. Inhibition of catalase may contribute to cell damage during incubation of cultures with L-DOPA, dopamine, or other autoxidizable compounds.
Han
S K
SK
Department of Neurology, Mount Sinai School of Medicine, City University of New York, NY 10029, USA.
Cohen
G
G
D000818:Animals; D002374:Catalase / Q000037:antagonists & inhibitors*; D002478:Cells, Cultured; D004298:Dopamine / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006873:Hydroquinones / Q000494:pharmacology; D007980:Levodopa / Q000494:pharmacology*; D008636:Mesencephalon / Q000187:drug effects* / Q000201:enzymology; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley
D004791:Enzyme Inhibitors; D006873:Hydroquinones; D007980:Levodopa; D002374:Catalase; D004298:Dopamine; C031927:hydroquinone