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Effects of Harmaline and Harmalol on Dopamine Quinone-induced Brain Mitochondrial Dysfunction  

Han, Eun-Sook (Department of Pharmacology, College of Medicine, Chung-Ang University)
Lee, Chung-Soo (Department of Pharmacology, College of Medicine, Chung-Ang University)
Publication Information
Biomolecules & Therapeutics / v.10, no.3, 2002 , pp. 152-158 More about this Journal
Abstract
The present study elucidated the effect of $\beta$-carbolines (harmaline and harmalol) on brain mitochondlial dysfunction caused by the tyrosinase-induced oxidation of dopamine. Harmaline, harmalol and antioxidant enzymes (SOD and catalase) attenuated the dopamine-induced alteration of membrane potential, cytochrome c release and thiol oxidation in mitochondria. In contrast, antioxidant enzymes failed to reverse mitochondrial dysfunction induced by dopmnine plus tyrosinase. $\beta$-Carbolines decreased the damaging effect of dopamine plus tyrosinase against mitochondria, except no effect of harmalol on thiol oxidation. Antioxidant enzymes decreased the melanin formation from dopamine in the reaction mixture containing mitochondria but did not reduce the formation of dopamine quinone caused by tyrosinase. Both harmalol and harmaline inhibited the formation of reactive quinone and melanin. Harmalol being more effective for quinone formation and vise versa. The results indicate that compared to MAO-induced dopamine oxidation, the toxic effect of dopamine in the presence of tyrosinase against mitochondria may be accomplished by the dopamine quinone and toxic substances other than reactive oxygen species. $\beta$-Carbolines may decrease the dopamine plus tyrosinase-induced brain mitochondrial dysfunction by inhibition of the formation of reactive quinone and the change in membrane permeability.
Keywords
$\beta$-carbolines; dopamine; tyrosinase; brain mitochondria; protection;
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